Search

Your search keyword '"John Powderly"' showing total 37 results
Start Over Author "John Powderly"
37 results on '"John Powderly"'

1. First-in-human phase 1 dose-escalation results with livmoniplimab, an antibody targeting the GARP:TGF-ß1 complex, as monotherapy and in combination with the anti–PD-1 antibody budigalimab in patients with advanced solid tumors

Author

Toshio Shimizu, John Powderly, Albiruni Abdul Razak, Patricia LoRusso, Kathy D. Miller, Steven Kao, Sarah Kongpachith, Catherine Tribouley, Michelle Graham, Brian Stoll, Maulik Patel, Mohammad Sahtout, Martha Blaney, Rachel Leibman, Talia Golan, and Anthony Tolcher

Subjects
advanced solid tumors, TGF-ß1, GARP, immunotherapy, anti-PD-1 antibody, combination drug therapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

BackgroundTransforming growth factor (TGF)-ß1 is a pleiotropic cytokine that can promote tumor growth and suppress antitumor immune responses. Latent TGF-ß1 associates with glycoprotein-A repetition predominant (GARP) on the surface of regulatory T cells prior to its activation and release. Livmoniplimab is a monoclonal antibody (mAb) that binds the GARP:TGF-ß1 complex to inhibit activation and release of TGF-ß1. It is in clinical development in combination with budigalimab, an anti-programmed cell death protein 1 Fc-modified mAb. The first-in-human, phase 1, dose-escalation results are presented herein (ClinicalTrials.gov: NCT03821935).MethodsThe dose-escalation phase enrolled adult patients with advanced solid tumors. Patients received escalating doses of livmoniplimab ranging from 3mg to 1500mg, once every 2 weeks (Q2W), as monotherapy or in combination with a 500mg fixed dose of budigalimab Q4W. The primary objective of the dose escalation was to determine the recommended phase 2 dose. Secondary objectives were to assess safety and pharmacokinetics (PK), and exploratory objectives included evaluating preliminary efficacy.ResultsFifty-seven patients enrolled in the dose escalation: 23 in monotherapy cohorts and 34 in combination therapy cohorts. Dose-limiting toxicities were limited, no maximum tolerated dose was reached, and the maximum administered dose of 1500mg was selected for dose expansion. The most common adverse events reported in monotherapy-treated patients were fatigue, anemia, and nausea, and those in combination therapy-treated patients were pruritus, fatigue, nausea, and anemia. Livmoniplimab exhibited dose-proportional PK, and peripheral blood biomarker data demonstrated saturation of the GARP:TGF-ß1 complex on platelets at livmoniplimab doses within the linear PK range. No objective tumor responses were observed in the monotherapy dose escalation. However, the objective response rate was 15% in the combination dose escalation, with a median response duration of 8.4 months.ConclusionLivmoniplimab was well-tolerated as monotherapy and in combination with budigalimab in the dose-escalation phase. Encouraging preliminary efficacy was demonstrated in the combination dose escalation in heavily pretreated patients, supporting further development of this novel drug combination in patients with advanced solid tumors.

Published
2024
Full Text
View/download PDF

2. 611 XTX202–01/02–001, Phase 1/2 first-in human study of XTX202, a masked, tumor-activated IL-2βγ, in patients with advanced solid tumors: results from phase 1

Author

David Miller, John Powderly, Suthee Rapisuwon, Sanjay Goel, Bartosz Chmielowski, Richard Wu, Meredith McKean, Damiano Fantini, Yousef Zakharia, Jacob Thomas, Diana Hanna, Anthony El-Khoueiry, Ekta Patel, Anurag Gupta, George Lee, Meghan Duncan, Meredith Pelster, Randy Hurley, Aika Siu, David Crowe, Sattanathan Paramasivan, and Katarina Luptakova

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2023
Full Text
View/download PDF

3. 750 A phase 1 trial of CUE-102, a novel WT1-pHLA-IL2-Fc fusion protein in HLA-A*0201 positive patients with WT1-positive recurrent/metastatic cancers

Author

Lei Zheng, Jun Gong, John Powderly, Tanios Bekaii-Saab, Angela Alistar, Siqing Fu, Nashat Gabrail, Dae Won Kim, Yvonne Saenger, Olatunji Alese, Apollina Goel, Nataliya Uboha, Laura Agensky, Matteo Levisetti, Steven Margossian, Steve Quayle, J Eva Selfridge, Jorge Chaves, and Jin Zhaohui

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2023
Full Text
View/download PDF

4. 717 A phase 1/2 study of AU-007, a monoclonal antibody (mAb) that binds to IL-2 and inhibits CD25 binding, in patients with advanced solid tumors: interim results from dose escalation

Author

Andrew Haydon, John Powderly, Timothy Wyant, James Vasselli, Drew Rasco, Meredith McKean, Elizabeth Ahern, Sophia Frentzas, Andrew Weickhardt, Inbar Amit, Aron Knickerbocker, Yanay Ofran, Paul de Souza, Jenny Tang, and Lori Richards

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2023
Full Text
View/download PDF

5. 710 Keynote-B59: dose escalation of a phase 1/2 first-in-human, open-label study of GI-101, a novel immunocytokine combining CD80-IL2v, in combination with pembrolizumab in advanced solid tumors

Author

John Powderly, Jae Lyun Lee, Jung-Yun Lee, Byoung Chul Cho, Kyoung-Ho Pyo, Soohyeon Lee, Dong Kim, Myoung Ho Jang, Byoung Yong Shim, Sang Joon Shin, Nari Yun, Mina Ham, Julia Cohen, Hyo Jin Lee, Kyoyoung Lee, Hyunjin Kang, Jea Hwan Kim, and Mi hyun Kim

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2023
Full Text
View/download PDF

6. Model Informed Dosing Regimen and Phase I Results of the Anti‐PD‐1 Antibody Budigalimab (ABBV‐181)

Author

John Powderly, Alexander Spira, Shunsuke Kondo, Toshihiko Doi, Jason J. Luke, Drew Rasco, Bo Gao, Minna Tanner, Philippe A. Cassier, Anas Gazzah, Antoine Italiano, Diego Tosi, Daniel E. Afar, Apurvasena Parikh, Benjamin Engelhardt, Stefan Englert, Stacie L. Lambert, Sreeneeranj Kasichayanula, Sven Mensing, Rajeev Menon, Gregory Vosganian, and Anthony Tolcher

Subjects
Therapeutics. Pharmacology, RM1-950, Public aspects of medicine, RA1-1270
Abstract

Budigalimab is a humanized, recombinant, Fc mutated IgG1 monoclonal antibody targeting programmed cell death 1 (PD‐1) receptor, currently in phase I clinical trials. The safety, efficacy, pharmacokinetics (PKs), pharmacodynamics (PDs), and budigalimab dose selection from monotherapy dose escalation and multihistology expansion cohorts were evaluated in patients with previously treated advanced solid tumors who received budigalimab at 1, 3, or 10 mg/kg intravenously every 2 weeks (Q2W) in dose escalation, including Japanese patients that received 3 and 10 mg/kg Q2W. PK modeling and PK/PD assessments informed the dosing regimen in expansion phase using data from body‐weight‐based dosing in the escalation phase, based on which patients in the multihistology expansion cohort received flat doses of 250 mg Q2W or 500 mg every four weeks (Q4W). Immune‐related adverse events (AEs) were reported in 11 of 59 patients (18.6%), of which 1 of 59 (1.7%) was considered grade ≥ 3 and the safety profile of budigalimab was consistent with other PD‐1 targeting agents. No treatment‐related grade 5 AEs were reported. Four responses per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 were reported in the dose escalation cohort and none in the multihistology expansion cohort. PK of budigalimab was approximately dose proportional and sustained > 99% peripheral PD‐1 receptor saturation was observed by 2 hours postdosing, across doses. PK/PD and safety profiles were comparable between Japanese and Western patients, and exposure‐safety analyses did not indicate any trends. Observed PK and PD‐1 receptor saturation were consistent with model predictions for flat doses and less frequent regimens, validating the early application of PK modeling and PK/PD assessments to inform the recommended dose and regimen, following dose escalation.

Published
2021
Full Text
View/download PDF

7. 518 First-in-human results with the novel tumor-targeting antibody ATRC-101: phase 1b study in patients with solid tumors

Author

Lixia Wang, John Powderly, Tanios Bekaii-Saab, Susanna Ulahannan, Ngan Nguyen, Deborah Doroshow, Yan Xing, Mark Whidden, Carl Millward, Jonathan Benjamin, S John Weroha, Frances Valdes-Albini, Kimberly Walter, Andrew Wrong, Paul Del Castillo, and Steven Isakoff

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2021
Full Text
View/download PDF

9. 373 Phase 1/2 study of subcutaneously administered ALKS 4230, a novel engineered cytokine, as monotherapy and in combination with pembrolizumab, in patients with advanced solid tumors: ARTISTRY-2

Author

Yan Wang, John Powderly, Marc Ernstoff, Anthony Shields, Ulka Vaishampayan, John Wrangle, Sarina Piha-Paul, Anthony Olszanski, Lei Sun, Bradley Carthon, Kelly Curtis, Ilda Bidollari, Yangchun Du, Emily Putiri, Heather Losey, and Bruce Dezube

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2020
Full Text
View/download PDF

10. Safety and Tolerability of MEDI0562, an OX40 Agonist mAb, in Combination with Durvalumab or Tremelimumab in Adult Patients with Advanced Solid Tumors

Author

Jonathan W. Goldman, Sarina A. Piha-Paul, Brendan Curti, Katrina S. Pedersen, Todd M. Bauer, Stefanie L. Groenland, Richard D. Carvajal, Vaishali Chhaya, Gray Kirby, Kelly McGlinchey, Scott A. Hammond, Katie Streicher, Danielle M. Townsley, Young Kwang Chae, Jens Voortman, Aurelien Marabelle, John Powderly, Internal medicine, CCA - Cancer Treatment and quality of life, and CCA - Imaging and biomarkers

Subjects
Adult, Cancer Research, Ki-67 Antigen, Oncology, Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Antibodies, Monoclonal, Humans, Antibodies, Monoclonal, Humanized
Abstract

Purpose: Combination therapies targeting immunologic checkpoints have shown promise in treating multiple tumor types. We report safety and tolerability of MEDI0562, a humanized IgG1K OX40 mAb, in combination with durvalumab (anti-PD-L1), or tremelimumab (anti-CTLA-4), in adult patients with previously treated advanced solid tumors. Patients and Methods: In this phase I, multicenter, open-label study, patients received escalating doses of MEDI0562 (2.25, 7.5, or 22.5 mg) every 2 weeks in combination with durvalumab (1,500 mg) or tremelimumab (75 or 225 mg) every 4 weeks, intravenously, until unacceptable toxicity or progressive disease. Tumor assessments were performed every 8 weeks. The primary objective was to evaluate safety and tolerability. Results: Among the 27 and 31 patients who received MEDI0562 + durvalumab or MEDI0562 + tremelimumab, 74.1% and 67.7% reported a treatment-related adverse event (AE), and 22.2% and 19.4% experienced a treatment-emergent AE that led to discontinuation, respectively. The MTD of MEDI0562 + durvalumab was 7.5 mg MEDI0562 + 1,500 mg durvalumab; the maximum administered dose of MEDI0562 + tremelimumab was 22.5 mg MEDI0562 + 225 mg tremelimumab. Three patients in the MEDI0562 + durvalumab arm had a partial response. The mean percentage of Ki67+CD4+ and Ki67+CD8+ memory T cells increased by >100% following the first dose of MEDI0562 + durvalumab or tremelimumab in all dose cohorts. A decrease in OX40+FOXP3 regulatory T cells was observed in a subset of patients with available paired biopsies. Conclusions: Following dose escalation, moderate toxicity was observed in both treatment arms, with no clear efficacy signals demonstrated.

Published
2022

12. Supplementary Data from Safety and Clinical Activity of Atezolizumab in Patients with Metastatic Castration-Resistant Prostate Cancer: A Phase I Study

Author

Thomas Powles, Susheela Carroll, Marcella Fassò, Sujata Narayanan, Carol O'Hear, Sanjeev Mariathasan, Edward E. Kadel, Kobe Yuen, Indrani Sarkar, Joseph W. Kim, Michael Gordon, Jean-Pierre Delord, Paul Conkling, Lauren C. Harshman, John Powderly, Fadi Braiteh, David R. Shaffer, Yohann Loriot, and Daniel P. Petrylak

Abstract

Supplement

Published
2023

13. Data from Phase I Study Utilizing a Novel Antigen-Presenting Cell–Targeted Vaccine with Toll-like Receptor Stimulation to Induce Immunity to Self-antigens in Cancer Patients

Author

H. Kim Lyerly, Timothy Clay, Thomas Davis, Takuya Osada, Amy Hobeika, Stephen A. Butler, Biwei Zhao, Laura Vitale, Venky Ramakrishna, Li-Zhen He, Renee Riggs, Jennifer Green, Tibor Keler, Kimberly Blackwell, John Powderly, Robert Chapman, and Michael A. Morse

Abstract

Purpose: The use of tumor-derived proteins as cancer vaccines is complicated by tolerance to these self-antigens. Tolerance may be broken by immunization with activated, autologous, ex vivo generated and antigen-loaded, antigen-presenting cells (APC); however, targeting tumor antigen directly to APC in vivo would be a less complicated strategy. We wished to test whether targeted delivery of an otherwise poorly immunogenic, soluble antigen to APC through their mannose receptors (MR) would induce clinically relevant immunity.Experimental Design: Two phase I studies were conducted with CDX-1307, a vaccine composed of human chorionic gonadotropin beta-chain (hCG-β) fused to an MR-specific monoclonal antibody, administered either locally (intradermally) or systemically (intravenously) in patients with advanced epithelial malignancies. An initial dose escalation of single-agent CDX-1307 was followed by additional cohorts of CDX-1307 combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) and the Toll-like receptor (TLR) 3 agonist polyinosinic-polycytidylic acid (poly-ICLC) and TLR7/8 agonist resiquimod to activate the APC.Results: CDX-1307 induced consistent humoral and T-cell responses to hCG-β when coadministered with TLR agonists. Greater immune responses and clinical benefit, including the longest duration of stable disease, were observed with immunization combined with local TLR agonists. Immune responses were induced equally efficiently in patients with elevated and nonelevated levels of serum hCG-β. Antibodies within the serum of vaccinated participants had tumor suppressive function in vitro. Toxicity consisted chiefly of mild injection site reactions.Conclusions: APC targeting and activation induce adaptive immunity against poorly immunogenic self-antigens which has implications for enhancing the efficacy of cancer immunotherapy. Clin Cancer Res; 17(14); 4844–53. ©2011 AACR.

Published
2023

14. Data from Safety and Clinical Activity of MEDI0562, a Humanized OX40 Agonist Monoclonal Antibody, in Adult Patients with Advanced Solid Tumors

Author

Sandip Pravin Patel, Danielle M. Townsley, Katie Streicher, Matthew Gribbin, Steven Eck, Yanan Zheng, Jennifer Burton, James P. Ohr, Sanjay Goel, Reva Schneider, Bhumsuk Keam, Naiyer A. Rizvi, John Powderly, Robert L. Ferris, Rom S. Leidner, and Bonnie S. Glisson

Abstract

Purpose:Immune checkpoint blockade has demonstrated clinical benefits across multiple solid tumor types; however, resistance and relapse often occur. New immunomodulatory targets, which are highly expressed in activated immune cells, are needed. MEDI0562, an agonistic humanized mAb, specifically binds to the costimulatory molecule OX40. This first-in-human study evaluated MEDI0562 in adults with advanced solid tumors.Patients and Methods:In this phase I, multicenter, open-label, single-arm, dose-escalation (3+3 design) study, patients received 0.03, 0.1, 0.3, 1.0, 3.0, or 10 mg/kg MEDI0562 through intravenous infusion every 2 weeks, until confirmed disease progression or unacceptable toxicity. The primary objective evaluated safety and tolerability. Secondary endpoints included antitumor activity, pharmacokinetics, immunogenicity, and pharmacodynamics.Results:In total, 55 patients received ≥1 dose of MEDI0562 and were included in the analysis. The most common tumor type was squamous cell carcinoma of the head and neck (47%). Median duration of treatment was 10 weeks (range, 2–48 weeks). Treatment-related adverse events (TRAEs) occurred in 67% of patients, most commonly fatigue (31%) and infusion-related reactions (14%). Grade 3 TRAEs occurred in 14% of patients with no apparent dose relationship; no TRAEs resulted in death. Two patients had immune-related partial responses per protocol and 44% had stable disease. MEDI0562 induced increased Ki67+ CD4+ and CD8+ memory T-cell proliferation in the periphery and decreased intratumoral OX40+ FOXP3+ cells.Conclusions:MEDI0562 was safely administered at doses up to 10 mg/kg in heavily pretreated patients. On-target pharmacodynamic effects were suggested in this setting. Further evaluation with immune checkpoint inhibitors is ongoing.

Published
2023

15. Data from Safety and Tolerability of MEDI0562, an OX40 Agonist mAb, in Combination with Durvalumab or Tremelimumab in Adult Patients with Advanced Solid Tumors

Author

John Powderly, Aurelien Marabelle, Jens Voortman, Young Kwang Chae, Danielle M. Townsley, Katie Streicher, Scott A. Hammond, Kelly McGlinchey, Gray Kirby, Vaishali Chhaya, Richard D. Carvajal, Stefanie L. Groenland, Todd M. Bauer, Katrina S. Pedersen, Brendan Curti, Sarina A. Piha-Paul, and Jonathan W. Goldman

Abstract

Purpose:Combination therapies targeting immunologic checkpoints have shown promise in treating multiple tumor types. We report safety and tolerability of MEDI0562, a humanized IgG1K OX40 mAb, in combination with durvalumab (anti-PD-L1), or tremelimumab (anti-CTLA-4), in adult patients with previously treated advanced solid tumors.Patients and Methods:In this phase I, multicenter, open-label study, patients received escalating doses of MEDI0562 (2.25, 7.5, or 22.5 mg) every 2 weeks in combination with durvalumab (1,500 mg) or tremelimumab (75 or 225 mg) every 4 weeks, intravenously, until unacceptable toxicity or progressive disease. Tumor assessments were performed every 8 weeks. The primary objective was to evaluate safety and tolerability.Results:Among the 27 and 31 patients who received MEDI0562 + durvalumab or MEDI0562 + tremelimumab, 74.1% and 67.7% reported a treatment-related adverse event (AE), and 22.2% and 19.4% experienced a treatment-emergent AE that led to discontinuation, respectively. The MTD of MEDI0562 + durvalumab was 7.5 mg MEDI0562 + 1,500 mg durvalumab; the maximum administered dose of MEDI0562 + tremelimumab was 22.5 mg MEDI0562 + 225 mg tremelimumab. Three patients in the MEDI0562 + durvalumab arm had a partial response. The mean percentage of Ki67+CD4+ and Ki67+CD8+ memory T cells increased by >100% following the first dose of MEDI0562 + durvalumab or tremelimumab in all dose cohorts. A decrease in OX40+FOXP3 regulatory T cells was observed in a subset of patients with available paired biopsies.Conclusions:Following dose escalation, moderate toxicity was observed in both treatment arms, with no clear efficacy signals demonstrated.

Published
2023

16. Supplementary Table 1 from Phase I Study Utilizing a Novel Antigen-Presenting Cell–Targeted Vaccine with Toll-like Receptor Stimulation to Induce Immunity to Self-antigens in Cancer Patients

Author

H. Kim Lyerly, Timothy Clay, Thomas Davis, Takuya Osada, Amy Hobeika, Stephen A. Butler, Biwei Zhao, Laura Vitale, Venky Ramakrishna, Li-Zhen He, Renee Riggs, Jennifer Green, Tibor Keler, Kimberly Blackwell, John Powderly, Robert Chapman, and Michael A. Morse

Abstract

Supplementary Table 1 from Phase I Study Utilizing a Novel Antigen-Presenting Cell–Targeted Vaccine with Toll-like Receptor Stimulation to Induce Immunity to Self-antigens in Cancer Patients

Published
2023

17. Supplementary Figure from Safety and Tolerability of MEDI0562, an OX40 Agonist mAb, in Combination with Durvalumab or Tremelimumab in Adult Patients with Advanced Solid Tumors

Author

John Powderly, Aurelien Marabelle, Jens Voortman, Young Kwang Chae, Danielle M. Townsley, Katie Streicher, Scott A. Hammond, Kelly McGlinchey, Gray Kirby, Vaishali Chhaya, Richard D. Carvajal, Stefanie L. Groenland, Todd M. Bauer, Katrina S. Pedersen, Brendan Curti, Sarina A. Piha-Paul, and Jonathan W. Goldman

Abstract

Supplementary Figure from Safety and Tolerability of MEDI0562, an OX40 Agonist mAb, in Combination with Durvalumab or Tremelimumab in Adult Patients with Advanced Solid Tumors

Published
2023

18. Supplementary Data from Safety and Tolerability of MEDI0562, an OX40 Agonist mAb, in Combination with Durvalumab or Tremelimumab in Adult Patients with Advanced Solid Tumors

Author

John Powderly, Aurelien Marabelle, Jens Voortman, Young Kwang Chae, Danielle M. Townsley, Katie Streicher, Scott A. Hammond, Kelly McGlinchey, Gray Kirby, Vaishali Chhaya, Richard D. Carvajal, Stefanie L. Groenland, Todd M. Bauer, Katrina S. Pedersen, Brendan Curti, Sarina A. Piha-Paul, and Jonathan W. Goldman

Abstract

Supplementary Data from Safety and Tolerability of MEDI0562, an OX40 Agonist mAb, in Combination with Durvalumab or Tremelimumab in Adult Patients with Advanced Solid Tumors

Published
2023

19. Data from Safety and Clinical Activity of Atezolizumab in Patients with Metastatic Castration-Resistant Prostate Cancer: A Phase I Study

Author

Thomas Powles, Susheela Carroll, Marcella Fassò, Sujata Narayanan, Carol O'Hear, Sanjeev Mariathasan, Edward E. Kadel, Kobe Yuen, Indrani Sarkar, Joseph W. Kim, Michael Gordon, Jean-Pierre Delord, Paul Conkling, Lauren C. Harshman, John Powderly, Fadi Braiteh, David R. Shaffer, Yohann Loriot, and Daniel P. Petrylak

Abstract

Purpose:Atezolizumab [anti–programmed death-ligand 1 (anti-PD-L1)] is well tolerated and efficacious in multiple cancers, but has not been previously evaluated in metastatic castration-resistant prostate cancer (mCRPC). This study examined the safety, efficacy, and biomarkers of atezolizumab monotherapy for mCRPC.Patients and Methods:This phase Ia, open-label, dose-escalation and dose-expansion study (PCD4989g) enrolled patients with mCRPC who had progressed on sipuleucel-T or enzalutamide. Atezolizumab was given intravenously every 3 weeks until confirmed disease progression or loss of clinical benefit. Prespecified endpoints included safety, efficacy, biomarker analyses, and radiographic assessments.Results:All 35 evaluable patients [median age, 68 years (range, 45–83 years)] received atezolizumab after ≥1 prior line of therapy; 62.9% of patients had received ≥3 prior lines. Treatment-related adverse events occurred in 21 patients (60.0%), with no deaths. One patient had a confirmed partial response (PR) per RECIST 1.1, and 1 patient had a PR per immune-related response criteria. The confirmed 50% PSA response rate was 8.6% (3 patients). Median overall survival (OS) was 14.7 months [95% confidence interval (CI): 5.9–not evaluable], with a 1-year OS rate of 52.3% (95% CI: 34–70); 2-year OS was 35.9% (95% CI: 13–59). Median follow-up was 13.0 months (range, 1.2–28.1 months). Biomarker analyses showed that atezolizumab activated immune responses; however, a composite biomarker failed to reveal consistent correlations with efficacy.Conclusions:Atezolizumab was generally well tolerated in patients with mCRPC, with a safety profile consistent with other tumor types. In heavily pretreated patients, atezolizumab monotherapy demonstrated evidence of disease control; however, its limited efficacy suggests a combination approach may be needed.

Published
2023

20. Phase 1/2 study of epacadostat in combination with durvalumab in patients with metastatic solid tumors

Author

Aung Naing, Alain P. Algazi, Gerald S. Falchook, Benjamin C. Creelan, John Powderly, Seth Rosen, Minal Barve, Niharika B. Mettu, Pierre L. Triozzi, John Hamm, Gongfu Zhou, Chris Walker, Zhiwan Dong, and Manish R. Patel

Subjects
Adult, Cancer Research, Sulfonamides, durvalumab, Clinical Trials and Supportive Activities, Oncology and Carcinogenesis, neoplasms, Evaluation of treatments and therapeutic interventions, epacadostat, Antibodies, kynurenine, Second Primary, Oncology, Clinical Research, 6.1 Pharmaceuticals, Oximes, Antineoplastic Combined Chemotherapy Protocols, Monoclonal, PD-1, Public Health and Health Services, Humans, Oncology & Carcinogenesis, Cancer
Abstract

BackgroundTargeting programmed cell death protein 1 (PD-1) and indoleamine 2,3-dioxygenase (IDO1) pathways is an appealing option for cancer treatment.MethodsThe open-label, phase 1/2 ECHO-203 study evaluated the safety, tolerability, and efficacy of the IDO1 inhibitor epacadostat in combination with durvalumab, a human anti-PD-L1 monoclonal antibody in adult patients with advanced solid tumors.ResultsThe most common treatment-related adverse events were fatigue (30.7%), nausea (21.0%), decreased appetite (13.1%), pruritus (12.5%), maculopapular rash (10.8%), and diarrhea (10.2%). Objective response rate (ORR) in the overall phase 2 population was 12.0%. Higher ORR was observed in immune checkpoint inhibitor (CPI)-naïve patients (16.1%) compared with patients who had received previous CPI (4.1%). Epacadostat pharmacodynamics were evaluated by comparing baseline kynurenine levels with those on therapy at various time points. Only the 300-mg epacadostat dose showed evidence of kynurenine modulation, albeit unsustained.ConclusionsEpacadostat plus durvalumab was generally well tolerated in patients with advanced solid tumors. ORR was low, and evaluation of kynurenine concentration from baseline to cycle 2,day 1, and cycle 5,day 1, suggested >300mg epacadostat twice daily is needed to ensure sufficient drug effect.Clinical trial informationA study of epacadostat (INCB024360) in combination with durvalumab (MEDI4736) in subjects with selected advanced solid tumors (ECHO-203) (NCT02318277).

Published
2023

23. 770 Safety, efficacy, and pharmacokinetic results from a phase I first-in-human study of ABBV-151 with or without anti-PD1 mAb (budigalimab) in patients with locally advanced or metastatic solid tumors

Author

Anthony Tolcher, Desamparados Roda-Perez, Kai He, Victor Moreno, Carlos Gomez-Roca, Jean-Pascal Machiels, Albiruni Razak, Mohammad Sahtout, Xiaowen Guan, Stacy Jaryno-Daly, Rachel Leibman, Martha Blaney, James O’Brien, Patricia Lorusso, John Powderly, Talia Golan, Kathy Miller, and Jordi Bruix

Published
2022

25. 636 A phase 1, open-label, dose escalation and expansion study of CUE-102 monotherapy in HLA-A*0201 positive patients with WT1-positive recurrent/metastatic cancers

Author

Steven Margossian, John Powderly, Nashat Gabrail, Yvonne Saenger, J Eva Selfridge, Nataliya Uboha, Jun Gong, Brian Van Tine, Olatunji Alese, Dae Won Kim, Wen Ma, Tanios Bekaii-Saab, Jeremy Jones, Angela Alistar, Laura Agensky, Apollina Goel, Reena Lynam, Raymond Moniz, Steve Quayle, Cynthia Rajan, Kenneth Pienta, and Matteo Levisetti

Published
2022

30. Abstract CT209: A first-in-human phase 1 trial of IO-108, an antagonist antibody targeting LILRB2 (ILT4), as monotherapy and in combination with pembrolizumab in adult patients with advanced relapsed or refractory solid tumors (NCT05054348)

Author

John Powderly, Manish Patel, Paul Woodard, Luke Chung, Hongyu Tian, Elizabeth Wieland, Kyu Hong, Maria Jose Costa, X. Charlene Liao, and Matthew Taylor

Subjects
Cancer Research, Oncology
Abstract

Cancer immunotherapy has entered the mainstream with approval of T-cell checkpoint inhibitors. However, most patients with advanced solid tumors do not derive benefits, or relapse after T-cell checkpoint blockade. Myeloid checkpoint inhibition is a new approach to cancer immunotherapy. LILRB2 is primarily expressed by myeloid cells and its expression in tumors is associated with high macrophage infiltration. Several LILRB2 ligands (HLA-G, ANGPTL2, and SEMA4A) are known to contribute to the immune suppressive microenvironment of solid tumors. Blockade of the LILRB2 pathway has the potential to reactivate or enhance anti-tumor T cell immune responses. IO-108 is a IgG4 monoclonal antibody that specifically binds LILRB2 to block ligands interaction and activation of LILRB2. In vitro, IO-108 treatment of primary immune cells results increased pro-inflammatory responses and an enhanced antigen presenting cell phenotypes. A Good Laboratory Practice repeat-dose, 15-day toxicology study in Cynomolgus monkeys at 0 (control), 1, 10, or 100 mg/kg/dose administered intravenously once weekly for a total of 3 doses showed that IO-108 was well-tolerated at all dose levels, with only non-statistically significant reduction of thyroid glands weight. No-observed-adverse-effect-level (NOAEL) of 100 mg/kg provides a sufficient safety margin for the IO-108 starting dose of 60 mg, which was derived using a MABEL (minimum anticipated biological effect level) approach. This clinical trial is a first-in-human, Phase 1, multicenter, open-label, dose-escalation, safety, pharmacokinetic (PK), and pharmacodynamic evaluation of intravenously administered IO-108, both as monotherapy and in combination with pembrolizumab, in adult patients with solid tumors that have failed standard of care therapies (NCT05054348). It is estimated that up to 36 patients will be enrolled in the study. IO-108 will be administered every 21 days, with a dose-limiting toxicity (DLT) evaluation period of 21 days. Patients will be enrolled into sequential cohorts and treated with increasing doses of IO-108 using mTPI (modified Toxicity Probability Interval) method. Safety, PK, and clinical activity will be evaluated on an ongoing basis. The primary objective of the study is to assess safety and tolerability at increasing dose levels of IO-108 in successive cohorts of adult patients (treated with or without with pembrolizumab) with advanced relapsed or refractory solid tumors, to estimate the maximal tolerated dose (MTD) or maximum administered dose (MAD) and select the recommended phase 2 dose (RP2D). Secondary objectives include characterizing PK, immunogenicity, and preliminary anti-tumor activity. Biomarker evaluation will include changes in myeloid cell markers and T-cells, LILRB2 expression level and receptor occupancy. Statistical analyses will be primarily descriptive in nature. Tabulations will be produced for appropriate disposition, demographic, baseline disease characteristics, safety, PK, pharmacodynamic, and clinical activity parameters. Response to treatment as assessed by RECIST v1.1 will be tabulated. To date, five patients have been dosed without DLT. Citation Format: John Powderly, Manish Patel, Paul Woodard, Luke Chung, Hongyu Tian, Elizabeth Wieland, Kyu Hong, Maria Jose Costa, X. Charlene Liao, Matthew Taylor. A first-in-human phase 1 trial of IO-108, an antagonist antibody targeting LILRB2 (ILT4), as monotherapy and in combination with pembrolizumab in adult patients with advanced relapsed or refractory solid tumors (NCT05054348) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT209.

Published
2022

31. Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study

Author

Marina Chiara Garassino, Byoung-Chul Cho, Joo-Hang Kim, Julien Mazières, Johan Vansteenkiste, Hervé Lena, Jesus Corral Jaime, Jhanelle E Gray, John Powderly, Christos Chouaid, Paolo Bidoli, Paul Wheatley-Price, Keunchil Park, Ross A Soo, Yifan Huang, Catherine Wadsworth, Phillip A Dennis, Naiyer A Rizvi, Luis Paz-Ares Rodriguez, Silvia Novello, Sandrine Hiret, Peter Schmid, Eckart Laack, Raffaele Califano, Makoto Maemondo, Sang-We Kim, Jamie Chaft, David Vicente Baz, Thierry Berghmans, Dong-Wan Kim, Veerle Surmont, Martin Reck, Ji-Youn Han, Esther Holgado Martin, Cristobal Belda Iniesta, Yuichiro Oe, Antonio Chella, Akhil Chopra, Gilles Robinet, Hector Soto Parra, Michael Thomas, Parneet Cheema, Nobuyuki Katakami, Wu-Chou Su, Young-Chul Kim, Juergen Wolf, Jong-Seok Lee, Hideo Saka, Michele Milella, Inmaculada Ramos Garcia, Anne Sibille, Takashi Yokoi, Eun Joo Kang, Shinji Atagi, Ernst Spaeth-Schwalbe, Makoto Nishio, Fumio Imamura, Nashat Gabrail, Remi Veillon, Sofie Derijcke, Tadashi Maeda, Dylan Zylla, Kendra Kubiak, Armando Santoro, Ma. Noemi Uy, Sarayut Lucien Geater, Antoine Italiano, Dariusz Kowalski, Fabrice Barlesi, Yuh-Min Chen, David Spigel, Busyamas Chewaskulyong, Ramon Garcia Gomez, Rosa Alvarez Alvarez, Chih-Hsin Yang, Te-Chun Hsia, Fabrice Denis, Hiroshi Sakai, Mark Vincent, Koichi Goto, Joaquim Bosch-Barrera, Glen Weiss, Jean-Luc Canon, Christian Scholz, Massimo Aglietta, Hirotsugu Kemmotsu, Koichi Azuma, Penelope Bradbury, Ronald Feld, Abraham Chachoua, Jacek Jassem, Rosalyn Juergens, Ramon Palmero Sanchez, Albert Malcolm, Nandagopal Vrindavanam, Kaoru Kubota, Cornelius Waller, David Waterhouse, Bruno Coudert, Zsuzsanna Mark, Miyako Satouchi, Gee-Chen Chang, Christian Herzmann, Arvind Chaudhry, Selvaraj Giridharan, Paul Hesketh, Norihiko Ikeda, Ralph Boccia, Nichola Iannotti, Missak Haigentz, John Reynolds, John Querol, Kazuhiko Nakagawa, Shunichi Sugawara, Eng Huat Tan, Tomonori Hirashima, Scott Gettinger, Terufumi Kato, Koji Takeda, Oscar Juan Vidal, Andrea Mohn-Staudner, Amit Panwalkar, Davey Daniel, Kunihiko Kobayashi, Guia Elena Imelda Ladrera, Clemens Schulte, Martin Sebastian, Marketa Cernovska, Helena Coupkova, Libor Havel, Norbert Pauk, Joginder Singh, Shuji Murakami, Tibor Csoszi, Gyorgy Losonczy, Allan Price, Ian Anderson, Mussawar Iqbal, Vamsee Torri, Erzsebet Juhasz, Saleem Khanani, Leona Koubkova, Benjamin Levy, Ray Page, Csaba Bocskei, Lucio Crinò, David Einspahr, Christopher Hagenstad, Necy Juat, Lindsay Overton, Mitchell Garrison, Zsuzsanna Szalai, IRCCS Istituto Nazionale dei Tumori [Milano], Yonsei University College of Medicine, CHA Bundang Medical Center, Service Pneumologie-Allergologie [CHU Toulouse], Pôle Clinique des Voies respiratoires [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), University Hospitals KU Leuven, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospital Universitario Virgen del Rocío [Sevilla], H. Lee Moffitt Cancer Center and Research Institute, Carolina BioOncology Institute, Service de Pneumologie [CHI Créteil], CHI Créteil, IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Azienda Ospedaliera San Gerardo, The Ottawa Hospital Research Institute, Centre for Rehabilitation Research and Development, 505 Smyth Road, Ottawa, ON, Canada, K1H 8M2., Samsung Medical Center Sungkyunkwan University School of Medicine, Institute Division of Hematology/Oncology, National University Hospital and National University Cancer Institute, AstraZeneca, Gaithersburg, MD, USA, AstraZeneca [Cambridge, UK], Columbia University [New York], Università degli studi di Torino = University of Turin (UNITO), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Department of Mathematics [Imperial College London], Imperial College London, Université libre de Bruxelles (ULB), Department of Microbiology, Chang Won National University, German Center for Lung Research, Università degli studi di Palermo - University of Palermo, Garassino, M, Cho, B, Kim, J, Mazieres, J, Vansteenkiste, J, Lena, H, Jaime, J, Gray, J, Powderly, J, Chouaid, C, Bidoli, P, Wheatley-Price, P, Park, K, Soo, R, Huang, Y, Wadsworth, C, Dennis, P, and Rizvi, N

Subjects
0301 basic medicine, Oncology, Male, Durvalumab, Lung Neoplasms, Phases of clinical research, B7-H1 Antigen, 0302 clinical medicine, Antineoplastic Agents, Immunological, 4-Butyrolactone, Carcinoma, Non-Small-Cell Lung, Anaplastic lymphoma kinase, Anaplastic Lymphoma Kinase, Fatigue, Antibodies, Monoclonal, phase 2 study, gamma-Glutamyltransferase, Middle Aged, Progression-Free Survival, ErbB Receptors, ATLANTIS, Response Evaluation Criteria in Solid Tumors, Oncology, Durvalumab, non-small-cell lung cancer , ATLANTIS, phase 2 study, 030220 oncology & carcinogenesis, Cohort, Female, Immunotherapy, Diarrhea, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, 03 medical and health sciences, Internal medicine, medicine, Humans, Progression-free survival, Aspartate Aminotransferases, Lung cancer, Aged, Performance status, business.industry, Pneumonia, medicine.disease, Injection Site Reaction, 030104 developmental biology, non-small-cell lung cancer, Mutation, business
Abstract

Background: Immune checkpoint inhibitors are a new standard of care for patients with advanced non-small-cell lung cancer (NSCLC) without EGFR tyrosine kinase or anaplastic lymphoma kinase (ALK) genetic aberrations (EGFR−/ALK−), but clinical benefit in patients with EGFR mutations or ALK rearrangements (EGFR+/ALK+) has not been shown. We assessed the effect of durvalumab (anti-PD-L1) treatment in three cohorts of patients with NSCLC defined by EGFR/ALK status and tumour expression of PD-L1. Methods: ATLANTIC is a phase 2, open-label, single-arm trial at 139 study centres in Asia, Europe, and North America. Eligible patients had advanced NSCLC with disease progression following at least two previous systemic regimens, including platinum-based chemotherapy (and tyrosine kinase inhibitor therapy if indicated); were aged 18 years or older; had a WHO performance status score of 0 or 1; and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Key exclusion criteria included mixed small-cell lung cancer and NSCLC histology; previous exposure to any anti-PD-1 or anti-PD-L1 antibody; and any previous grade 3 or worse immune-related adverse event while receiving any immunotherapy agent. Patients in cohort 1 had EGFR+/ALK+ NSCLC with at least 25%, or less than 25%, of tumour cells with PD-L1 expression. Patients in cohorts 2 and 3 had EGFR−/ALK− NSCLC; cohort 2 included patients with at least 25%, or less than 25%, of tumour cells with PD-L1 expression, and cohort 3 included patients with at least 90% of tumour cells with PD-L1 expression. Patients received durvalumab (10 mg/kg) every 2 weeks, via intravenous infusion, for up to 12 months. Retreatment was allowed for patients who benefited but then progressed after completing 12 months. The primary endpoint was the proportion of patients with increased tumour expression of PD-L1 (defined as ≥25% of tumour cells in cohorts 1 and 2, and ≥90% of tumour cells in cohort 3) who achieved an objective response, assessed in patients who were evaluable for response per independent central review according to RECIST version 1.1. Safety was assessed in all patients who received at least one dose of durvalumab and for whom any post-dose data were available. The trial is ongoing, but is no longer open to accrual, and is registered with ClinicalTrials.gov, number NCT02087423. Findings: Between Feb 25, 2014, and Dec 28, 2015, 444 patients were enrolled and received durvalumab: 111 in cohort 1, 265 in cohort 2, and 68 in cohort 3. Among patients with at least 25% of tumour cells expressing PD-L1 who were evaluable for objective response per independent central review, an objective response was achieved in 9 (12·2%, 95% CI 5·7–21·8) of 74 patients in cohort 1 and 24 (16·4%, 10·8–23·5) of 146 patients in cohort 2. In cohort 3, 21 (30·9%, 20·2–43·3) of 68 patients achieved an objective response. Grade 3 or 4 treatment-related adverse events occurred in 40 (9%) of 444 patients overall: six (5%) of 111 patients in cohort 1, 22 (8%) of 265 in cohort 2, and 12 (18%) of 68 in cohort 3. The most common treatment-related grade 3 or 4 adverse events were pneumonitis (four patients [1%]), elevated gamma-glutamyltransferase (four [1%]), diarrhoea (three [1%]), infusion-related reaction (three [1%]), elevated aspartate aminotransferase (two [

Published
2020

32. 373 Phase 1/2 study of subcutaneously administered ALKS 4230, a novel engineered cytokine, as monotherapy and in combination with pembrolizumab, in patients with advanced solid tumors: ARTISTRY-2

Author

John Powderly, Bradley Carthon, Marc Ernstoff, Anthony Olszanski, John Wrangle, Anthony Shields, Sarina Piha-Paul, Kelly Curtis, Ilda Bidollari, Yangchun Du, Lei Sun, Emily Putiri, Yan Wang, Heather Losey, Bruce Dezube, and Ulka Vaishampayan

Subjects
Oncology, medicine.medical_specialty, Combination therapy, business.industry, Pembrolizumab, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, Tolerability, Pharmacokinetics, Pharmacodynamics, Internal medicine, Medicine, Chills, Dosing, medicine.symptom, business, Adverse effect
Abstract

Background ALKS 4230 is a novel engineered cytokine designed to selectively bind and activate the intermediate affinity IL-2 receptor. Intravenous (IV) dosing of ALKS 4230 has shown encouraging efficacy and acceptable tolerability, as monotherapy and in combination with pembrolizumab, in patients with advanced solid tumors (ARTISTRY-1, NCT02799095). Subcutaneous (SC) dosing may be preferable to IV in certain clinical situations. Methods ARTISTRY-2 (NCT03861793) is an ongoing phase 1/2 study of SC ALKS 4230 ± pembrolizumab. In phase 1, cohort-specific doses of SC ALKS 4230 are administered on either an every-7-day (q7d) or every-21-day (q21d) schedule during a 6-week lead-in period, followed by combination with IV pembrolizumab 200 mg q21d. Each patient assigned to a given cohort receives ALKS 4230 at a single dose level and on a schedule of either q7d or q21d. Safety, tolerability, dose-limiting toxicities (DLTs), and pharmacokinetics/pharmacodynamics from dose escalation, as of 7/24/2020 are reported in this abstract. Results 38 patients have been treated with ALKS 4230 across 7 assigned cohorts, with SC doses ranging from 0.3 mg to 10 mg (median age, 61.5 [28–82] years; median number of prior therapies 4 [0–17]; 45% were previously treated with immunotherapy). 25 patients completed monotherapy and initiated combination therapy. Median duration of treatment was 64.5 (1–506) days. Systemic exposure to ALKS 4230 increased with increasing dose, resulting in a dose dependent increase in circulating natural killer and CD8+ T cells, without significant impact on regulatory T cells. Overall, adverse events (AEs), regardless of causality, occurred in 33 (86.8%) patients. Treatment-related AEs (TRAEs; investigator assessed) occurred in 32 (84.2%) patients, and the most common TRAEs are presented in table 1. One patient experienced a serious TRAE, a grade 3 tumor flare manifesting as colonic obstruction. The maximum tolerated dose as well as recommended phase 2 dose for SC administration has not yet been determined. Conclusions ALKS 4230 is a promising investigational agent for the treatment of advanced solid tumors. The SC safety profile is consistent with the known and anticipated pharmacologic effects of ALKS 4230. Consistent with IV dosing, SC administration of ALKS 4230 q7d or q21d maintained the desired immune responses as demonstrated by pharmacodynamic outcomes. Potentially lower rates of fever and chills observed, relative to IV dosing, are presumed to be consistent with lower peak concentrations achieved so far via the SC route. The study, including dose escalation, is ongoing. Acknowledgements The authors would like to thank all the patients who are participating in this study. The study is sponsored by Alkermes, Inc. Medical writing and editorial support was provided by Parexel and funded by Alkermes, Inc. Trial Registration ClinicalTrials. gov NCT03861793 Ethics Approval This study was approved by Ethics and Institutional Review Boards (IRBs) at all study sites; IRB reference numbers 20182543 (Western IRB), 00006731 (Roswell Park Comprehensive Cancer Center), STUDY00000056 (Georgetown University, MedStar Health Research Institute).

Published
2020

33. Preliminary Phase 1 Results of the PD-1 Inhibitor ABBV-181 in Japanese vs Western Patients With Advanced Solid Tumors

Author

Kuboki, Yasutoshi, primary, Kondo, Shunsuke, additional, Drew, Rasco, additional, John, Powderly, additional, Alexander, Spira, additional, luke Jason, J., additional, Daniel, Afar, additional, Stefan, Englert, additional, Hashiba, Hideyuki, additional, Stacie, Lambert, additional, Apurvasena, Parikh, additional, Shimizu, Eisuke, additional, Greg, Vosganian, additional, Doi, Toshihiko, additional, and Yamamoto, Noboru, additional

Published
2019
Full Text
View/download PDF

34. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): late breaking abstracts

Author

Sonja Althammer, Keith Steele, Marlon Rebelatto, Tze Heng Tan, Tobias Wiestler, Guenter Schmidt, Brandon Higgs, Xia Li, Li Shi, Xiaoping Jin, Joyce Antal, Ashok Gupta, Koustubh Ranade, Gerd Binning, Joaquim Bellmunt, Ronald de Wit, David J. Vaughn, Yves Fradet, Jae Lyun Lee, Lawrence Fong, Nicholas J. Vogelzang, Miguel A. Climent, Daniel P. Petrylak, Toni K. Choueiri, Andrea Necchi, Winald Gerritsen, Howard Gurney, David I. Quinn, Stéphane Culine, Cora N. Sternberg, Yabing Mai, Markus Puhlmann, Rodolfo F. Perini, Dean F. Bajorin, Padmanee Sharma, Margaret K. Callahan, Emiliano Calvo, Joseph W. Kim, Filipo de Braud, Patrick A. Ott, Petri Bono, Rathi N. Pillai, Michael Morse, Dung T. Le, Matthew Taylor, Pavlina Spilliopoulou, Johanna Bendell, Dirk Jaeger, Emily Chan, Scott J. Antonia, Paolo A. Ascierto, Delphine Hennicken, Marina Tschaika, Alex Azrilevich, Jonathan Rosenberg, Ofer Levy, Christopher Chan, Gady Cojocaru, Spencer Liang, Eran Ophir, Sudipto Ganguly, Amir Toporik, Maya Kotturi, Tal Fridman Kfir, Benjamin M. Murter, Kathryn Logronio, Liat Dassa, Ling Leung, Shirley Greenwald, Meir Azulay, Sandeep Kumar, Zoya Alteber, Xiaoyu Pan, Arthur Machlenkin, Yair Benita, Andrew W. Drake, Ayelet Chajut, Ran Salomon, Ilan Vankin, Einav Safyon, John Hunter, Zurit Levine, Mark White, Rom Leidner, Hyunseok Kang, Robert Haddad, Neil H. Segal, Lori J. Wirth, Robert L. Ferris, F. Stephen Hodi, Rachel E. Sanborn, Thomas F. Gajewski, William Sharfman, Dan McDonald, Shivani Srivastava, Xuemin Gu, Penny Phillips, Chaitali Passey, Tanguy Seiwert, Tsadik Habtetsion, Gang Zhou, Donastas Sakellariou-Thompson, Cara Haymaker, Caitlin Creasy, Mark Hurd, Naohiro Uraoka, Jaime Rodriguez Canales, Scott Koptez, Patrick Hwu, Anirban Maitra, Chantale Bernatchez, Scott M. Coyle, Kole T. Roybel, Levi J. Rupp, Stephen P. Santoro, Stephanie Secrest, Michael Spelman, Hanson Ho, Tina Gomes, Tiffany Tse, Chia Yung-Wu, Jack Taunton, Wendell Lim, Peter Emtage, Tarsem Moudgil, Carmen Ballesteros-Merino, Traci Hilton, Christopher Paustian, David Page, Walter Urba, Bernard Fox, Bryan Bell, Ashish Patel, Tove Olafsen, Daulet Satpayev, Michael Torgov, Filippo Marchioni, Jason Romero, Ziyue Karen Jiang, Charles Zamilpa, Jennifer S. Keppler, Alessandro Mascioni, Fang Jia, Chen-Yu Lee, Jean Gudas, Ryan J. Sullivan, Yujin Hoshida, Theodore Logan, Nikhil Khushalani, Anita Giobbie-Hurder, Kim Margolin, Joanna Roder, Rupal Bhatt, Henry Koon, Thomas Olencki, Thomas Hutson, Brendan Curti, Shauna Blackmon, James W. Mier, Igor Puzanov, Heinrich Roder, John Stewart, Asim Amin, Marc S. Ernstoff, Joseph I. Clark, Michael B. Atkins, Howard L. Kaufman, Jeffrey Sosman, Sabina Signoretti, David F. McDermott, Abraham A. Anderson, Mohammed M. Milhem, Robert H. I. Andtbacka, David Minor, Kevin S. Gorski, Daniel M. Baker, Omid Hamid, Emmanuel Akporiaye, Yoshinobu Koguchi, Kim Sutcliffe, Kristie Conder, Thomas Marron, Nina Bhardwaj, Linda Hammerich, Fiby George, Seunghee Kim-Schulze, Tibor Keler, Tom Davis, Elizabeth Crowley, Andres Salazar, Joshua Brody, Arta Monjazeb, Megan E. Daly, Jonathan Riess, Tianhong Li, William J. Murphy, Karen Kelly, Zhiwei Hu, Rulong Shen, Amanda Campbell, Elizabeth McMichael, Lianbo Yu, Bhuvaneswari Ramaswam, Cheryl A. London, Tian Xu, William Carson, Kathleen M. Kokolus, Elizabeth A. Repasky, Todd D. Schell, Joseph D. Drabick, David J. Messenheimer, Shawn Jensen, Mark Rubinstein, Kristina Andrijauskaite, Marzena Swiderska-syn, Kristin Lind, Agnes Choppin, Marina K. Roell, John Wrangle, Peter Rhode, Hing Wong, Shamim Ahmad, Mason Webb, Rasha Abu-Eid, Rajeev Shrimali, Vivek Verma, Atbin Doroodchi, Zuzana Berrong, David Yashar, Raed Samara, Mikayel Mkrtichyan, Samir Khleif, Steven Powell, Mark Gitau, Christopher Sumey, Andrew Terrell, Michele Lohr, Ryan K. Nowak, Steven McGraw, Ash Jensen, Miran Blanchard, Kathryn A. Gold, Ezra E. W. Cohen, Christie Ellison, Lora Black, John Lee, William Chad Spanos, Erik Wennerberg, Emily Schwitzer, Claire Lhuillier, Graeme Koelwyn, Rebecca Hiner, Lee Jones, Sandra Demaria, Vandeveer Amanda, John W. Greiner, Jeffrey Schlom, Michelle Bookstaver, Christopher M. Jewell, Andrew Gunderson, Brian Boulmay, Rui Li, Bradley Spieler, Kyle Happel, Zipei Feng, Christopher Dubay, Brenda Fisher, Sandra Aung, Eileen Mederos, Carlo B. Bifulco, Michael McNamara, Keith Bahjat, William Redmond, Augusto Ochoa, Hong-Ming Hu, Adi Mehta, Fridtjof Lund-Johansen, Frank Bedu-Addo, Greg Conn, Michael King, Panna Dutta, Robert Shepard, Mark Einstein, Sylvia Adams, Ena Wang, Ping Jin, Yelena Novik, Debra Morrison, Ruth Oratz, Franco M. Marincola, David Stroncek, Judith Goldberg, Silvia C. Formenti, Jérôme Galon, Bernhard Mlecnik, Florence Marliot, Fang-Shu Ou, Alessandro Lugli, Inti Zlobec, Tilman T. Rau, Iris D. Nagtegaal, Elisa Vink-Borger, Arndt Hartmann, Carol Geppert, Michael H. Roehrl, Prashant Bavi, Pamela S. Ohashi, Julia Y. Wang, Linh T. Nguyen, SeongJun Han, Heather L. MacGregor, Sara Hafezi-Bakhtiari, Bradley G. Wouters, Yutaka Kawakami, Boryana Papivanova, Mingli Xu, Tomonobu Fujita, Shoichi Hazama, Nobuaki Suzuki, Hiroaki Nagano, Kiyotaka Okuno, Kyogo Itoh, Eva Zavadova, Michal Vocka, Jan Spacek, Lubos Petruzelka, Bohuslav Konopasek, Pavel Dundr, Helena Skalova, Toshihiko Torigoe, Noriyuki Sato, Tomohisa Furuhata, Ichiro Takemasa, Marc Van den Eynde, Anne Jouret-Mourin, Jean-Pascal Machiels, Tessa Fredriksen, Lucie Lafontaine, Bénédicte Buttard, Sarah Church, Pauline Maby, Helen Angell, Mihaela Angelova, Angela Vasaturo, Gabriela Bindea, Anne Berger, Christine Lagorce, Prabhu S. Patel, Hemangini H. Vora, Birva Shah, Jayendrakumar B. Patel, Kruti N. Rajvik, Shashank J. Pandya, Shilin N. Shukla, Yili Wang, Guanjun Zhang, Giuseppe V. Masucci, Emilia K. Andersson, Fabio Grizzi, Luigi Laghi, Gerardo Botti, Fabiana Tatangelo, Paolo Delrio, Gennaro Cilberto, Franco Marincola, Daniel J. Sargent, Bernard A. Fox, Alain Algazi, Katy Tsai, Michael Rosenblum, Prachi Nandoskar, Amy Li, John Nonomura, Kathryn Takamura, Mary Dwyer, Erica Browning, Reneta Talia, Chris Twitty, Sharron Gargosky, Jean Campbell, Mai Le, Robert H. Pierce, Adil Daud, Robyn Gartrell, Douglas Marks, Edward Stack, Yan Lu, Daisuke Izaki, Kristen Beck, Dan Tong Jia, Paul Armenta, Ashley White-Stern, Yichun Fu, Zoe Blake, Bret Taback, Basil Horst, Yvonne M. Saenger, Steven Leonardo, Keith Gorden, Ross B. Fulton, Kathryn Fraser, Takashi O. Kangas, Richard Walsh, Kathleen Ertelt, Jeremy Graff, Mark Uhlik, Jennifer S. Sims, Liang Lei, Takashi Tsujiuchi, Jeffrey N. Bruce, Peter Canoll, Anthony W Tolcher, Evan W Alley, Gurunadh Chichili, Jan E Canoll, Paul Moore, Ezio Bonvini, Syd Johnson, Sadhna Shankar, James Vasselli, Jon Wigginton, and John Powderly

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Durvalumab, medicine.medical_treatment, Immunology, Improved survival, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Immunology and Allergy, Pharmacology, business.industry, Cancer, Immunotherapy, medicine.disease, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Molecular Medicine, Non small cell, business
Abstract

O1 Combinatorial CD8+ and PD-L1+ cell densities correlate with response and improved survival in non-small cell lung cancer (NSCLC) patients treated with durvalumab #### Sonja Althammer1, Keith Steele2, Marlon Rebelatto2, Tze Heng Tan1, Tobias Wiestler1, Guenter Schmidt1, Brandon Higgs2, Xia

Published
2016

35. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part one

Author

Andreas Lundqvist, Vincent van Hoef, Xiaonan Zhang, Erik Wennerberg, Julie Lorent, Kristina Witt, Laia Masvidal Sanz, Shuo Liang, Shannon Murray, Ola Larsson, Rolf Kiessling, Yumeng Mao, John-William Sidhom, Catherine A. Bessell, Jonathan Havel, Jonathan Schneck, Timothy A. Chan, Eliot Sachsenmeier, David Woods, Anders Berglund, Rupal Ramakrishnan, Andressa Sodre, Jeffrey Weber, Roberta Zappasodi, Yanyun Li, Jingjing Qi, Philip Wong, Cynthia Sirard, Michael Postow, Walter Newman, Henry Koon, Vamsidhar Velcheti, Margaret K. Callahan, Jedd D. Wolchok, Taha Merghoub, Lawrence G. Lum, Minsig Choi, Archana Thakur, Abhinav Deol, Gregory Dyson, Anthony Shields, Cara Haymaker, Marc Uemura, Ravi Murthy, Marihella James, Daqing Wang, Julie Brevard, Catherine Monaghan, Suzanne Swann, James Geib, Mark Cornfeld, Srinivas Chunduru, Sudhir Agrawal, Cassian Yee, Jennifer Wargo, Sapna P. Patel, Rodabe Amaria, Hussein Tawbi, Isabella Glitza, Scott Woodman, Wen-Jen Hwu, Michael A. Davies, Patrick Hwu, Willem W. Overwijk, Chantale Bernatchez, Adi Diab, Erminia Massarelli, Neil H. Segal, Vincent Ribrag, Ignacio Melero, Tara C. Gangadhar, Walter Urba, Dirk Schadendorf, Robert L. Ferris, Roch Houot, Franck Morschhauser, Theodore Logan, Jason J. Luke, William Sharfman, Fabrice Barlesi, Patrick A. Ott, Laura Mansi, Shivaani Kummar, Gilles Salles, Cecilia Carpio, Roland Meier, Suba Krishnan, Dan McDonald, Matthew Maurer, Xuemin Gu, Jaclyn Neely, Satyendra Suryawanshi, Ronald Levy, Nikhil Khushalani, Jennifer Wu, Jinyu Zhang, Fahmin Basher, Mark Rubinstein, Mark Bucsek, Guanxi Qiao, Cameron MacDonald, Bonnie Hylander, Elizabeth Repasky, Shilpak Chatterjee, Anusara Daenthanasanmak, Paramita Chakraborty, Kyle Toth, Megan Meek, Elizabeth Garrett-Mayer, Michael Nishimura, Chrystal Paulos, Craig Beeson, Xuezhong Yu, Shikhar Mehrotra, Fei Zhao, Kathy Evans, Christine Xiao, Alisha Holtzhausen, Brent A. Hanks, Nicole Scharping, Ashley V. Menk, Rebecca Moreci, Ryan Whetstone, Rebekah Dadey, Simon Watkins, Robert Ferris, Greg M. Delgoffe, Jonathan Peled, Sean Devlin, Anna Staffas, Melissa Lumish, Kori Porosnicu Rodriguez, Katya Ahr, Miguel Perales, Sergio Giralt, Ying Taur, Eric Pamer, Marcel R. M. van den Brink, Robert Jenq, Nicola Annels, Hardev Pandha, Guy Simpson, Hugh Mostafid, Kevin Harrington, Alan Melcher, Mark Grose, Bronwyn Davies, Gough Au, Roberta Karpathy, Darren Shafren, Jacob Ricca, Dmitriy Zamarin, Luciana Batista, Florence Marliot, Angela Vasaturo, Sabrina Carpentier, Cécile Poggionovo, Véronique Frayssinet, Jacques Fieschi, Marc Van den Eynde, Franck Pagès, Jérôme Galon, Fabienne Hermitte, Sean G. Smith, Khue Nguyen, Sruthi Ravindranathan, Bhanu Koppolu, David Zaharoff, Gustavo Schvartsman, Roland Bassett, Jennifer L. McQuade, Lauren E. Haydu, Douglas Kline, Xiufen Chen, Dominick Fosco, Justin Kline, Abigail Overacre, Maria Chikina, Erin Brunazzi, Gulidanna Shayan, William Horne, Jay Kolls, Tullia C. Bruno, Creg Workman, Dario Vignali, Prasad S. Adusumilli, Ephraim A Ansa-Addo, Zihai Li, Andrew Gerry, Joseph P. Sanderson, Karen Howe, Roslin Docta, Qian Gao, Eleanor A. L. Bagg, Nicholas Tribble, Miguel Maroto, Gareth Betts, Natalie Bath, Luca Melchiori, Daniel E. Lowther, Indu Ramachandran, Gabor Kari, Samik Basu, Gwendolyn Binder-Scholl, Karen Chagin, Lini Pandite, Tom Holdich, Rafael Amado, Hua Zhang, John Glod, Donna Bernstein, Bent Jakobsen, Crystal Mackall, Ryan Wong, Jonathan D. Silk, Katherine Adams, Garth Hamilton, Alan D. Bennett, Sara Brett, Junping Jing, Adriano Quattrini, Manoj Saini, Guy Wiedermann, Joanna Brewer, MyLinh Duong, An Lu, Peter Chang, Aruna Mahendravada, Nicholas Shinners, Kevin Slawin, David M. Spencer, Aaron E. Foster, J. Henri Bayle, Cristina Bergamaschi, Sinnie Sin Man Ng, Bethany Nagy, Shawn Jensen, Xintao Hu, Candido Alicea, Bernard Fox, Barbara Felber, George Pavlakis, Jessica Chacon, Tori Yamamoto, Thomas Garrabrant, Luis Cortina, Daniel J. Powell, Marco Donia, Julie Westerlin Kjeldsen, Rikke Andersen, Marie Christine Wulff Westergaard, Valentina Bianchi, Mateusz Legut, Meriem Attaf, Garry Dolton, Barbara Szomolay, Sascha Ott, Rikke Lyngaa, Sine Reker Hadrup, Andrew Kelvin Sewell, Inge Marie Svane, Aaron Fan, Takumi Kumai, Esteban Celis, Ian Frank, Amanda Stramer, Michelle A. Blaskovich, Seth Wardell, Maria Fardis, James Bender, Michael T. Lotze, Stephanie L. Goff, Nikolaos Zacharakis, Yasmine Assadipour, Todd D. Prickett, Jared J. Gartner, Robert Somerville, Mary Black, Hui Xu, Harshini Chinnasamy, Isaac Kriley, Lily Lu, John Wunderlich, Paul F. Robbins, Steven Rosenberg, Steven A. Feldman, Kasia Trebska-McGowan, Parisa Malekzadeh, Eden Payabyab, Richard Sherry, Aishwarya Gokuldass, Charlene Kopits, Brian Rabinovich, Daniel S. Green, Olena Kamenyeva, Kathryn C. Zoon, Christina M. Annunziata, Joanne Hammill, Christopher Helsen, Craig Aarts, Jonathan Bramson, Yui Harada, Yoshikazu Yonemitsu, Kenneth Mwawasi, Galina Denisova, Rajanish Giri, Benjamin Jin, Tracy Campbell, Lindsey M. Draper, Sanja Stevanovic, Zhiya Yu, Bianca Weissbrich, Nicholas P. Restifo, Cornelia L. Trimble, Christian S. Hinrichs, Kwong Tsang, Massimo Fantini, James W. Hodge, Rika Fujii, Ingrid Fernando, Caroline Jochems, Christopher Heery, James Gulley, Patrick Soon-Shiong, Jeffrey Schlom, Weiqing Jing, Jill Gershan, Grace Blitzer, James Weber, Laura McOlash, Bryon D. Johnson, Simin Kiany, Huang Gangxiong, Eugenie S. Kleinerman, Michael Klichinsky, Marco Ruella, Olga Shestova, Saad Kenderian, Miriam Kim, John Scholler, Carl H. June, Saar Gill, Duane Moogk, Shi Zhong, Ivan Liadi, William Rittase, Victoria Fang, Janna Dougherty, Arianne Perez-Garcia, Iman Osman, Cheng Zhu, Navin Varadarajan, Alan Frey, Michelle Krogsgaard, Daniel Landi, Kristen Fousek, Malini Mukherjee, Ankita Shree, Sujith Joseph, Kevin Bielamowicz, Tiara Byrd, Nabil Ahmed, Meenakshi Hegde, Sylvia Lee, David Byrd, John Thompson, Shailender Bhatia, Scott Tykodi, Judy Delismon, Liz Chu, Siddiq Abdul-Alim, Arpy Ohanian, Anna Marie DeVito, Stanley Riddell, Kim Margolin, Isabelle Magalhaes, Jonas Mattsson, Michael Uhlin, Satoshi Nemoto, Patricio Pérez Villarroel, Ryosuke Nakagawa, James J. Mule, Adam W. Mailloux, Melinda Mata, Phuong Nguyen, Claudia Gerken, Christopher DeRenzo, Stephen Gottschalk, Mélissa Mathieu, Sandy Pelletier, John Stagg, Simon Turcotte, Nicholas Minutolo, Prannda Sharma, Andrew Tsourkas, Nadine Mockel-Tenbrinck, Daniela Mauer, Katharina Drechsel, Carola Barth, Katharina Freese, Ulrike Kolrep, Silke Schult, Mario Assenmacher, Andrew Kaiser, John Mullinax, MacLean Hall, Julie Le, Krithika Kodumudi, Erica Royster, Allison Richards, Ricardo Gonzalez, Amod Sarnaik, Shari Pilon-Thomas, Morten Nielsen, Anders Krarup-Hansen, Dorrit Hovgaard, Michael Mørk Petersen, Anand Chainsukh Loya, Niels Junker, Charlotte Rivas, Robin Parihar, Cliona M. Rooney, Haiying Qin, Sang Nguyen, Paul Su, Chad Burk, Brynn Duncan, Bong-Hyun Kim, M. Eric Kohler, Terry Fry, Arjun A. Rao, Noam Teyssier, Jacob Pfeil, Nikolaos Sgourakis, Sofie Salama, David Haussler, Sarah A. Richman, Selene Nunez-Cruz, Zack Gershenson, Zissimos Mourelatos, David Barrett, Stephan Grupp, Michael Milone, Alba Rodriguez-Garcia, Matthew K. Robinson, Gregory P. Adams, João Santos, Riikka Havunen, Mikko Siurala, Víctor Cervera-Carrascón, Suvi Parviainen, Marjukka Antilla, Akseli Hemminki, Jyothi Sethuraman, Laurelis Santiago, Jie Qing Chen, Zhimin Dai, Huizi Sha, Shu Su, Naiqing Ding, Baorui Liu, Anna Pasetto, Sarah R. Helman, Steven A. Rosenberg, Melissa Burgess, Hui Zhang, Tien Lee, Hans Klingemann, Paul Nghiem, John M. Kirkwood, John M. Rossi, Marika Sherman, Allen Xue, Yueh-wei Shen, Lynn Navale, James N. Kochenderfer, Adrian Bot, Anandaraman Veerapathran, Doris Wiener, Edmund K. Waller, Jian-Ming Li, Christopher Petersen, Bruce R. Blazar, Jingxia Li, Cynthia R. Giver, Ziming Wang, Steven K. Grossenbacher, Ian Sturgill, Robert J. Canter, William J. Murphy, Congcong Zhang, Michael C. Burger, Lukas Jennewein, Anja Waldmann, Michel Mittelbronn, Torsten Tonn, Joachim P. Steinbach, Winfried S. Wels, Jason B. Williams, Yuanyuan Zha, Thomas F. Gajewski, LaTerrica C. Williams, Giedre Krenciute, Mamta Kalra, Chrystal Louis, Gang Xin, David Schauder, Aimin Jiang, Nikhil Joshi, Weiguo Cui, Xue Zeng, Zeguo Zhao, Mohamad Hamieh, Justin Eyquem, Gertrude Gunset, Neil Bander, Michel Sadelain, David Askmyr, Milad Abolhalaj, Kristina Lundberg, Lennart Greiff, Malin Lindstedt, Helen K. Angell, Kyoung-Mee Kim, Seung-Tae Kim, Sung Kim, Alan D. Sharpe, Julia Ogden, Anna Davenport, Darren R. Hodgson, Carl Barrett, Jeeyun Lee, Elaine Kilgour, Jodi Hanson, Richard Caspell, Alexey Karulin, Paul Lehmann, Tameem Ansari, Annemarie Schiller, Srividya Sundararaman, Diana Roen, Mark Ayers, Diane Levitan, Gladys Arreaza, Fang Liu, Robin Mogg, Yung-Jue Bang, Bert O’Neil, Razvan Cristescu, Philip Friedlander, Karl Wassman, Chrisann Kyi, William Oh, Nina Bhardwaj, Svetlana Bornschlegl, Michael P. Gustafson, Dennis A. Gastineau, Ian F. Parney, Allan B. Dietz, Daniel Carvajal-Hausdorf, Nikita Mani, Kurt Schalper, David Rimm, Serena Chang, John Kurland, Christoph Matthias Ahlers, Maria Jure-Kunkel, Lewis Cohen, Holden Maecker, Holbrook Kohrt, Shuming Chen, George Crabill, Theresa Pritchard, Tracee McMiller, Drew Pardoll, Fan Pan, Suzanne Topalian, Patrick Danaher, Sarah Warren, Lucas Dennis, Andrew M. White, Leonard D’Amico, Melissa Geller, Mary L. Disis, Joseph Beechem, Kunle Odunsi, Steven Fling, Roshanak Derakhshandeh, Tonya J. Webb, Sigrid Dubois, Kevin Conlon, Bonita Bryant, Jennifer Hsu, Nancy Beltran, Jürgen Müller, Thomas Waldmann, Rebekka Duhen, Thomas Duhen, Lucas Thompson, Ryan Montler, Andrew Weinberg, Max Kates, Brandon Early, Erik Yusko, Taylor H. Schreiber, Trinity J. Bivalacqua, Jared Lunceford, Michael Nebozhyn, Erin Murphy, Andrey Loboda, David R. Kaufman, Andrew Albright, Jonathan Cheng, S. Peter Kang, Veena Shankaran, Sarina A. Piha-Paul, Jennifer Yearley, Tanguy Seiwert, Antoni Ribas, Terrill K. McClanahan, Xinwei Sher, Xiao Qiao Liu, Andrew Joe, Elizabeth Plimack, Alex Forrest-Hay, Cheryl A. Guyre, Kohei Narumiya, Marc Delcommenne, Heather A. Hirsch, Amit Deshpande, Jason Reeves, Jenny Shu, Tong Zi, Jennifer Michaelson, Debbie Law, Elizabeth Trehu, Sriram Sathyanaryanan, Brendan P. Hodkinson, Natalie A. Hutnick, Michael E. Schaffer, Michael Gormley, Tyler Hulett, Carmen Ballesteros-Merino, Christopher Dubay, Michael Afentoulis, Ashok Reddy, Larry David, Kumar Jayant, Swati Agrawal, Rajendra Agrawal, Ghayathri Jeyakumar, Seongho Kim, Heejin Kim, Cynthia Silski, Stacey Suisham, Elisabeth Heath, Ulka Vaishampayan, Natalie Vandeven, Natasja Nielsen Viller, Alison O’Connor, Hui Chen, Bolette Bossen, Eric Sievers, Robert Uger, Lisa Johnson, Hsiang-Fong Kao, Chin-Fu Hsiao, Shu-Chuan Lai, Chun-Wei Wang, Jenq-Yuh Ko, Pei-Jen Lou, Tsai-Jan Lee, Tsang-Wu Liu, Ruey-Long Hong, Staci J. Kearney, Joshua C. Black, Benjamin J. Landis, Sally Koegler, Brooke Hirsch, Roberto Gianani, Jeffrey Kim, Ming-Xiao He, Bingqing Zhang, Nan Su, Yuling Luo, Xiao-Jun Ma, Emily Park, Dae Won Kim, Domenico Copploa, Nishi Kothari, Young doo Chang, Richard Kim, Namyong Kim, Melvin Lye, Ee Wan, Hanna A. Knaus, Sofia Berglund, Hubert Hackl, Judith E. Karp, Ivana Gojo, Leo Luznik, Henoch S. Hong, Sven D. Koch, Birgit Scheel, Ulrike Gnad-Vogt, Karl-Josef Kallen, Volker Wiegand, Linus Backert, Oliver Kohlbacher, Ingmar Hoerr, Mariola Fotin-Mleczek, James M. Billingsley, Yoshinobu Koguchi, Valerie Conrad, William Miller, Iliana Gonzalez, Tomasz Poplonski, Tanisha Meeuwsen, Ana Howells-Ferreira, Rogan Rattray, Mary Campbell, Carlo Bifulco, Keith Bahjat, Brendan Curti, E-K Vetsika, G. Kallergi, Despoina Aggouraki, Z. Lyristi, P. Katsarlinos, Filippos Koinis, V. Georgoulias, Athanasios Kotsakis, Nathan T. Martin, Famke Aeffner, Logan Cerkovnik, Luke Pratte, Rebecca Kim, Joseph Krueger, Amaia Martínez-Usatorre, Camilla Jandus, Alena Donda, Laura Carretero-Iglesia, Daniel E. Speiser, Dietmar Zehn, Nathalie Rufer, Pedro Romero, Anshuman Panda, Janice Mehnert, Kim M. Hirshfield, Greg Riedlinger, Sherri Damare, Tracie Saunders, Levi Sokol, Mark Stein, Elizabeth Poplin, Lorna Rodriguez-Rodriguez, Ann Silk, Nancy Chan, Melissa Frankel, Michael Kane, Jyoti Malhotra, Joseph Aisner, Howard L. Kaufman, Siraj Ali, Jeffrey Ross, Eileen White, Gyan Bhanot, Shridar Ganesan, Anne Monette, Derek Bergeron, Amira Ben Amor, Liliane Meunier, Christine Caron, Antigoni Morou, Daniel Kaufmann, Moishe Liberman, Igor Jurisica, Anne-Marie Mes-Masson, Kamel Hamzaoui, Rejean Lapointe, Ann Mongan, Yuan-Chieh Ku, Warren Tom, Yongming Sun, Alex Pankov, Tim Looney, Janice Au-Young, Fiona Hyland, Jeff Conroy, Carl Morrison, Sean Glenn, Blake Burgher, He Ji, Mark Gardner, Angela R. Omilian, Wiam Bshara, Omilian Angela, Joseph M. Obeid, Gulsun Erdag, Mark E. Smolkin, Donna H. Deacon, James W. Patterson, Lieping Chen, Timothy N. Bullock, Craig L. Slingluff, John T. Loffredo, Raja Vuyyuru, Sophie Beyer, Vanessa M. Spires, Maxine Fox, Jon M. Ehrmann, Katrina A. Taylor, Alan J. Korman, Robert F. Graziano, David Page, Katherine Sanchez, Maritza Martel, Mariana Petaccia De Macedo, Yong Qin, Alex Reuben, Christine Spencer, Michele Guindani, Adriana Racolta, Brian Kelly, Tobin Jones, Nathan Polaske, Noah Theiss, Mark Robida, Jeffrey Meridew, Iva Habensus, Liping Zhang, Lidija Pestic-Dragovich, Lei Tang, Ryan J. Sullivan, Thomas Olencki, Thomas Hutson, Joanna Roder, Shauna Blackmon, Heinrich Roder, John Stewart, Asim Amin, Marc S. Ernstoff, Joseph I. Clark, Michael B. Atkins, Jeffrey Sosman, David F. McDermott, Harriet Kluger, Ruth Halaban, Mario Snzol, Senait Asmellash, Arni Steingrimsson, Chichung Wang, Kristin Roman, Amanda Clement, Sean Downing, Clifford Hoyt, Nathalie Harder, Guenter Schmidt, Ralf Schoenmeyer, Nicolas Brieu, Mehmet Yigitsoy, Gabriele Madonna, Gerardo Botti, Antonio Grimaldi, Paolo A. Ascierto, Ralf Huss, Maria Athelogou, Harald Hessel, Alexander Buchner, Christian Stief, Gerd Binnig, Thomas Kirchner, Shankar Sellappan, Sheeno Thyparambil, Sarit Schwartz, Fabiola Cecchi, Andrew Nguyen, Charles Vaske, Todd Hembrough, Jan Spacek, Michal Vocka, Eva Zavadova, Helena Skalova, Pavel Dundr, Lubos Petruzelka, Nicole Francis, Rau T. Tilman, Arndt Hartmann, Irena Netikova, Julia Stump, Amanda Tufman, Frank Berger, Michael Neuberger, Rudolf Hatz, Michael Lindner, Rachel E. Sanborn, John Handy, Rudolf M. Huber, Hauke Winter, Simone Reu, Cheng Sun, Weihua Xiao, Zhigang Tian, Kshitij Arora, Niyati Desai, Anupriya Kulkarni, Mihir Rajurkar, Miguel Rivera, Vikram Deshpande, David Ting, Katy Tsai, Adi Nosrati, Simone Goldinger, Omid Hamid, Alain Algazi, Paul Tumeh, Jimmy Hwang, Jacqueline Liu, Lawrence Chen, Reinhard Dummer, Michael Rosenblum, Adil Daud, Tsu-Shuen Tsao, Julia Ashworth-Sharpe, Donald Johnson, Srabani Bhaumik, Christopher Bieniarz, Joseph Couto, Michael Farrell, Mahsa Ghaffari, Antony Hubbard, Jerome Kosmeder, Cleo Lee, Erin Marner, Diana Uribe, Hongjun Zhang, Jian Zhang, Wenjun Zhang, Yifei Zhu, Larry Morrison, Takahiro Tsujikawa, Rohan N. Borkar, Vahid Azimi, Sushil Kumar, Guillaume Thibault, Motomi Mori, Edward El Rassi, Daniel R. Clayburgh, Molly F. Kulesz-Martin, Paul W. Flint, Lisa M. Coussens, Lisa Villabona, Giuseppe V. Masucci, Gary Geiss, Brian Birditt, Qian Mei, Alan Huang, Maribeth A. Eagan, Eduardo Ignacio, Nathan Elliott, Dwayne Dunaway, Jaemyeong Jung, Chris Merritt, Isaac Sprague, Philippa Webster, Yan Liang, Jessica Wenthe, Gunilla Enblad, Hannah Karlsson, Magnus Essand, Barbara Savoldo, Gianpietro Dotti, Martin Höglund, Malcolm K. Brenner, Hans Hagberg, Angelica Loskog, Matthew J. Bernett, Gregory L. Moore, Michael Hedvat, Christine Bonzon, Seung Chu, Rumana Rashid, Kendra N. Avery, Umesh Muchhal, John Desjarlais, Matthew Kraman, Katarzyna Kmiecik, Natalie Allen, Mustapha Faroudi, Carlo Zimarino, Mateusz Wydro, Jacqueline Doody, Sreesha P. Srinivasa, Nagaraja Govindappa, Praveen Reddy, Aparajita Dubey, Sankar Periyasamy, Madhukara Adekandi, Chaitali Dey, Mary Joy, Pieter Fokko van Loo, Henrike Veninga, Setareh Shamsili, Mark Throsby, Harry Dolstra, Lex Bakker, Ajjai Alva, Juergen Gschwendt, Yohann Loriot, Joaquim Bellmunt, Dai Feng, Christian Poehlein, Thomas Powles, Emmanuel S. Antonarakis, Charles G. Drake, Haiyan Wu, Johann De Bono, Rajat Bannerji, John Byrd, Gareth Gregory, Stephen Opat, Jake Shortt, Andrew J. Yee, Noopur Raje, Seth Thompson, Arun Balakumaran, Shaji Kumar, Brian I. Rini, Toni K. Choueiri, Mariangela Mariani, Laurence Albiges, John B. Haanen, James Larkin, Manuela Schmidinger, Domenico Magazzù, Alessandra di Pietro, Robert J. Motzer, Troels Holz Borch, Per Kongsted, Magnus Pedersen, Özcan Met, Karim Boudadi, Hao Wang, James Vasselli, Jan E. Baughman, Jon Wigginton, Rehab Abdallah, Ashley Ross, Jiwon Park, Steven Grossenbacher, Jesus I. Luna, Sita Withers, William Culp, Mingyi Chen, Arta Monjazeb, Michael S. Kent, Smita Chandran, David Danforth, James Yang, Christopher Klebanoff, Stephanie Goff, Biman Paria, Arvind Sabesan, Abhishek Srivastava, Udai Kammula, Jon Richards, Mark Faries, Robert H. I. Andtbacka, Luis A. Diaz, Dung T. Le, Takayuki Yoshino, Thierry André, Johanna Bendell, Minori Koshiji, Yayan Zhang, S Peter Kang, Bao Lam, Dirk Jäger, Todd M. Bauer, Judy S. Wang, Jean K. Lee, Gulam A. Manji, Ragini Kudchadkar, John S. Kauh, Shande Tang, Naomi Laing, Gerald Falchook, Edward B. Garon, Balazs Halmos, Hui Rina, Natasha Leighl, Sung Sook Lee, William Walsh, Konstanin Dragnev, Bilal Piperdi, Luis Paz-Ares Rodriguez, Nabeegha Shinwari, Ziewn Wei, Mary L Maas, Michael Deeds, Adam Armstrong, Tim Peterson, Sue Steinmetz, Thomas Herzog, Floor J. Backes, Larry Copeland, Maria Del Pilar Estevez Diz, Thomas W. Hare, Warner Huh, Byoung-Gie Kim, Kathleen M. Moore, Ana Oaknin, William Small, Krishnansu S. Tewari, Bradley J. Monk, Ashish M. Kamat, Kijoeng Nam, Maria De Santis, Robert Dreicer, Noah M. Hahn, Rodolfo Perini, Arlene Siefker-Radtke, Guru Sonpavde, Ronald de Wit, J. Alfred Witjes, Stephen Keefe, Dean Bajorin, Philippe Armand, John Kuruvilla, Craig Moskowitz, Mehdi Hamadani, Pier Luigi Zinzani, Sabine Chlosta, Nancy Bartlett, Rachel Sabado, Yvonne Saenger, Loging William, Michael Joseph Donovan, Erlinda Sacris, John Mandeli, Andres M. Salazar, John Powderly, Joshua Brody, John Nemunaitis, Leisha Emens, Amita Patnaik, Ian McCaffery, Richard Miller, Ginna Laport, Andrew L. Coveler, David C. Smith, Juneko E. Grilley-Olson, Sanjay Goel, Shyra J. Gardai, Che-Leung Law, Gary Means, Thomas Manley, Kristen A. Marrone, Gary Rosner, Valsamo Anagnostou, Joanne Riemer, Jessica Wakefield, Cynthia Zanhow, Stephen Baylin, Barbara Gitlitz, Julie Brahmer, Sabina Signoretti, Wenting Li, Charles Schloss, Jean-Marie Michot, Wei Ding, Beth Christian, Patricia Marinello, Margaret Shipp, Yana G. Najjar, null Lin, Lisa H. Butterfield, Ahmad A. Tarhini, Diwakar Davar, Hassane Zarour, Elizabeth Rush, Cindy Sander, Siqing Fu, Todd Bauer, Chris Molineaux, Mark K. Bennett, Keith W. Orford, Kyriakos P. Papadopoulos, Sukhmani K. Padda, Sumit A. Shah, A Dimitrios Colevas, Sujata Narayanan, George A. Fisher, Dana Supan, Heather A. Wakelee, Rhonda Aoki, Mark D. Pegram, Victor M. Villalobos, Jie Liu, Chris H. Takimoto, Mark Chao, Jens-Peter Volkmer, Ravindra Majeti, Irving L. Weissman, Branimir I. Sikic, Wendy Yu, Alison Conlin, Janet Ruzich, Stacy Lewis, Anupama Acheson, Kathleen Kemmer, Kelly Perlewitz, Nicole M. Moxon, Staci Mellinger, Heather McArthur, Trine Juhler-Nøttrup, Jayesh Desai, Ben Markman, Shahneen Sandhu, Hui Gan, Michael L. Friedlander, Ben Tran, Tarek Meniawy, Joanne Lundy, Duncan Colyer, Malaka Ameratunga, Christie Norris, Jason Yang, Kang Li, Lai Wang, Lusong Luo, Zhen Qin, Song Mu, Xuemei Tan, James Song, Michael Millward, Matthew H. G. Katz, Todd W. Bauer, Gauri R. Varadhachary, Nicolas Acquavella, Nipun Merchant, Gina Petroni, Osama E. Rahma, Mei Chen, Yang Song, Markus Puhlmann, Arun Khattri, Ryan Brisson, Christopher Harvey, Jatin Shah, Maria Victoria Mateos, Morio Matsumoto, Hilary Blacklock, Albert Oriol Rocafiguera, Hartmut Goldschmidt, Shinsuke Iida, Dina Ben Yehuda, Enrique Ocio, Paula Rodríguez-Otero, Sundar Jagannath, Sagar Lonial, Uma Kher, Jesus San-Miguel, Moacyr Ribeiro de Oliveira, Habte Yimer, Robert Rifkin, Fredrik Schjesvold, Razi Ghori, Anna Spreafico, Victor Lee, Roger K. C. Ngan, Ka Fai To, Myung Ju Ahn, Quan Sing Ng, Jin-Ching Lin, Ramona F. Swaby, Christine Gause, Sanatan Saraf, Anthony T. C. Chan, Elaine Lam, Nizar M. Tannir, Funda Meric-Bernstam, Matt Gross, Andy MacKinnon, Sam Whiting, Martin Voss, Evan Y. Yu, Mark R. Albertini, Erik A. Ranheim, Jacquelyn A. Hank, Cindy Zuleger, Thomas McFarland, Jennifer Collins, Erin Clements, Sharon Weber, Tracey Weigel, Heather Neuman, Greg Hartig, David Mahvi, MaryBeth Henry, Jacek Gan, Richard Yang, Lakeesha Carmichael, KyungMann Kim, Stephen D. Gillies, Paul M. Sondel, Vivek Subbiah, Lori Noffsinger, Kyle Hendricks, Marnix Bosch, Jay M. Lee, Mi-Heon Lee, Jonathan W. Goldman, Felicita E. Baratelli, Dorthe Schaue, Gerald Wang, Frances Rosen, Jane Yanagawa, Tonya C. Walser, Ying Q. Lin, Sharon Adams, Franco M. Marincola, Paul C. Tumeh, Fereidoun Abtin, Robert Suh, Karen Reckamp, William D. Wallace, Gang Zeng, David A. Elashoff, Sherven Sharma, Steven M. Dubinett, Anna C. Pavlick, Brian Gastman, Brent Hanks, Tibor Keler, Tom Davis, Laura A. Vitale, Elad Sharon, Chihiro Morishima, Martin Cheever, Christopher R. Heery, Joseph W. Kim, Elizabeth Lamping, Jennifer Marte, Sheri McMahon, Lisa Cordes, Farhad Fakhrejahani, Ravi Madan, Rachel Salazar, Maggie Zhang, Christoph Helwig, James L Gulley, Roger Li, John Amrhein, Zvi Cohen, Monique Champagne, Ashish Kamat, M. Angela Aznar, Sara Labiano, Angel Diaz-Lagares, Manel Esteller, Juan Sandoval, Susannah D. Barbee, David I. Bellovin, John C. Timmer, Nebiyu Wondyfraw, Susan Johnson, Johanna Park, Amanda Chen, Mikayel Mkrtichyan, Amir S. Razai, Kyle S. Jones, Chelsie Y. Hata, Denise Gonzalez, Quinn Deveraux, Brendan P. Eckelman, Luis Borges, Rukmini Bhardwaj, Raj K. Puri, Akiko Suzuki, Pamela Leland, Bharat H. Joshi, Todd Bartkowiak, Ashvin Jaiswal, Casey Ager, Midan Ai, Pratha Budhani, Renee Chin, David Hong, Michael Curran, William D. Hastings, Maria Pinzon-Ortiz, Masato Murakami, Jason R. Dobson, David Quinn, Joel P. Wagner, Xianhui Rong, Pamela Shaw, Ernesta Dammassa, Wei Guan, Glenn Dranoff, Alexander Cao, Ross B. Fulton, Steven Leonardo, Kathryn Fraser, Takashi O. Kangas, Nadine Ottoson, Nandita Bose, Richard D. Huhn, Jeremy Graff, Jamie Lowe, Keith Gorden, Mark Uhlik, Thomas O’Neill, Jenifer Widger, Andrea Crocker, Li-Zhen He, Jeffrey Weidlick, Karuna Sundarapandiyan, Venky Ramakrishna, James Storey, Lawrence J. Thomas, Joel Goldstein, Henry C. Marsh, Jamison Grailer, Julia Gilden, Pete Stecha, Denise Garvin, Jim Hartnett, Frank Fan, Mei Cong, Zhi-jie Jey Cheng, Marlon J. Hinner, Rachida-Siham Bel Aiba, Corinna Schlosser, Thomas Jaquin, Andrea Allersdorfer, Sven Berger, Alexander Wiedenmann, Gabriele Matschiner, Julia Schüler, Ulrich Moebius, Christine Rothe, Olwill A. Shane, Brendan Horton, Stefani Spranger, Dayson Moreira, Tomasz Adamus, Xingli Zhao, Piotr Swiderski, Sumanta Pal, Marcin Kortylewski, Alyssa Kosmides, Kevin Necochea, Kathleen M. Mahoney, Sachet A. Shukla, Nikolaos Patsoukis, Apoorvi Chaudhri, Hung Pham, Ping Hua, Xia Bu, Baogong Zhu, Nir Hacohen, Catherine J. Wu, Edward Fritsch, Vassiliki A. Boussiotis, Gordon J. Freeman, Amy E. Moran, Fanny Polesso, Lisa Lukaesko, Emelie Rådestad, Lars Egevad, Berit Sundberg, Lars Henningsohn, Victor Levitsky, William Rafelson, John L. Reagan, Loren Fast, Pottayil Sasikumar, Naremaddepalli Sudarshan, Raghuveer Ramachandra, Nagesh Gowda, Dodheri Samiulla, Talapaneni Chandrasekhar, Sreenivas Adurthi, Jiju Mani, Rashmi Nair, Amit Dhudashia, Nagaraj Gowda, Murali Ramachandra, Alexander Sankin, Benjamin Gartrell, Kerwin Cumberbatch, Hongying Huang, Joshua Stern, Mark Schoenberg, Xingxing Zang, Ryan Swanson, Michael Kornacker, Lawrence Evans, Erika Rickel, Martin Wolfson, Sandrine Valsesia-Wittmann, Tala Shekarian, François Simard, Rodrigo Nailo, Aurélie Dutour, Anne-Catherine Jallas, Christophe Caux, and Aurélien Marabelle

Subjects
Pharmacology, 0303 health sciences, Cancer Research, Side effect, business.industry, medicine.drug_class, Immunology, Phases of clinical research, Monoclonal antibody, Phase i study, Clinical trial, 03 medical and health sciences, 0302 clinical medicine, Oncology, Pharmacokinetics, 030220 oncology & carcinogenesis, Molecular Medicine, Immunology and Allergy, Medicine, In patient, Programmed death 1, business, 030304 developmental biology
Published
2016

37. Five-Year Follow-Up of Nivolumab in Previously Treated Advanced Non-Small-Cell Lung Cancer: Results From the CA209-003 Study.

Author

Gettinger S, Horn L, Jackman D, Spigel D, Antonia S, Hellmann M, Powderly J, Heist R, Sequist LV, Smith DC, Leming P, Geese WJ, Yoon D, Li A, and Brahmer J

Subjects
Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Immunological administration & dosage, Antineoplastic Agents, Immunological adverse effects, Female, Follow-Up Studies, Humans, Male, Middle Aged, Nivolumab adverse effects, Survival Rate, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy, Nivolumab administration & dosage
Abstract

Purpose In two phase III studies, nivolumab, a programmed death-1 (PD-1) inhibitor antibody, improved overall survival (OS) versus docetaxel in pretreated advanced non-small-cell lung cancer (NSCLC). We report 5-year follow-up results from an early phase I study of nivolumab in this patient population and describe characteristics of 5-year survivors. Patients and Methods Patients with pretreated, advanced NSCLC received nivolumab 1, 3, or 10 mg/kg every 2 weeks in 8-week cycles for up to 96 weeks. OS from the time of first dose was estimated by the Kaplan-Meier method. Results The estimated 5-year OS rate was 16% for all treated patients (N = 129); 5-year OS rates were similar for squamous (16%) and nonsquamous (15%) NSCLC. Of 16 5-year survivors, most (88%) were known current or former smokers. Of 10 5-year survivors with quantifiable PD-1 ligand 1 expression, 70% had ≥ 1% PD-1 ligand 1 expression at baseline. Twelve 5-year survivors (75%) achieved a partial response to nivolumab per Response Evaluation Criteria in Solid Tumors, version 1.0, and two each (12%) had stable disease and progressive disease as best response. Nine 5-year survivors (56%) completed the maximum 96 weeks of nivolumab; four (25%) discontinued owing to adverse events and three (19%) owing to disease progression. As of a November 2016 database lock, 12 5-year survivors (75%) received no subsequent therapy and were without evidence of progressive disease at last follow-up. Conclusions Nivolumab treatment resulted in long-term OS and durable responses in a proportion of patients with pretreated advanced NSCLC. Long-term survivors had diverse baseline and on-treatment characteristics.

Published
2018
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results