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1. Prospective manipulation of the gut microbiome with microbial ecosystem therapeutic 4 (MET4) in HPV-related locoregionally-advanced oropharyngeal cancer squamous cell carcinoma (LA-OPSCC) undergoing primary chemoradiation: ROMA2 study

Author

Oliva, Marc, Heirali, Alya, Watson, Geoffrey, Rooney, Ashley M., Cochrane, Kyla, Jennings, Sarah, Taylor, Rachel, Xu, Minge, Hosni, Ali, Hope, Andrew, Bratman, Scott V., Chepeha, Douglas, Weinreb, Ilan, Perez-Ordonez, Bayardo, Nin, Ricard Mesia, Waldron, John, Xu, Wei, Hansen, Aaron R., Siu, Lillian L., Coburn, Bryan, and Spreafico, Anna

Published
2024
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2. Smoking and alcohol by HPV status in head and neck cancer: a Mendelian randomization study

Author

Thakral, Abhinav, Lee, John JW., Hou, Tianzhichao, Hueniken, Katrina, Dudding, Tom, Gormley, Mark, Virani, Shama, Olshan, Andrew, Diergaarde, Brenda, Ness, Andrew R., Waterboer, Tim, Smith-Byrne, Karl, Brennan, Paul, Hayes, D. Neil, Sanderson, Eleanor, Brown, M. Catherine, Huang, Sophie, Bratman, Scott V., Spreafico, Anna, De Almeida, John, Davies, Joel C., Bierut, Laura, Macfarlane, Gary J., Lagiou, Pagona, Lagiou, Areti, Polesel, Jerry, Agudo, Antonio, Alemany, Laia, Ahrens, Wolfgang, Healy, Claire M., Conway, David I., Nygard, Mari, Canova, Cristina, Holcatova, Ivana, Richiardi, Lorenzo, Znaor, Ariana, Goldstein, David P., Hung, Rayjean J., Xu, Wei, Liu, Geoffrey, and Espin-Garcia, Osvaldo

Published
2024
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4. Multimodal detection of molecular residual disease in high-risk locally advanced squamous cell carcinoma of the head and neck

Author

Sanz-Garcia, Enrique, Zou, Jinfeng, Avery, Lisa, Spreafico, Anna, Waldron, John, Goldstein, David, Hansen, Aaron, Cho, B. C. John, de Almeida, John, Hope, Andrew, Hosni, Ali, Hahn, Ezra, Perez-Ordonez, Bayardo, Zhao, Zhen, Smith, Christopher, Zheng, Yangqiao, Singaravelan, Nitthusha, Bratman, Scott V., and Siu, Lillian L.

Published
2024
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5. The prognostic value of image-identified extranodal extension in laryngeal and hypopharyngeal carcinoma following definitive (chemo-)radiotherapy

Author

Alsheikh, Sulaiman, Su, Jie, O’Sullivan, Brian, Ringash, Jolie, Waldron, John N, V Bratman, Scott, Cho, John, Sanz Garcia, Enrique, Spreafico, Anna, de Almeida, John, Hahn, Ezra, Hope, Andrew, Hosni, Ali, Kim, John, McPartlin, Andrew, Tsai, Jillian, Li, Tong, Xu, Wei, Yu, Eugene, and Huang, Shao Hui

Published
2024
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6. A Phase II, Open-Label, Randomized Trial of Durvalumab With Olaparib or Cediranib in Patients With Mismatch Repair—Proficient Colorectal or Pancreatic Cancer

Author

Hernando-Calvo, Alberto, Han, Ming, Ayodele, Olubukola, Wang, Ben X., Bruce, Jeffrey P., Abbas-Aghababazadeh, Farnoosh, Vila-Casadesús, Maria, Sanz-Garcia, Enrique, Yang, S.Y. Cindy, Berman, Hal K., Vivancos, Ana, Lam, Bernard, Lungu, Ilinca, Salawu, Abdulazeez, Stayner, Lee-Anne, Haibe-Kains, Benjamin, Bedard, Philippe L., Avery, Lisa, Razak, Albiruni R.A., Pugh, Trevor J., Spreafico, Anna, Siu, Lillian L., and Hansen, Aaron R.

Published
2024
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8. Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT)

Author

Genta, Sofia, Lajkosz, Katherine, Yee, Noelle R., Spiliopoulou, Pavlina, Heirali, Alya, Hansen, Aaron R., Siu, Lillian L., Saibil, Sam, Stayner, Lee-Anne, Yanekina, Maryia, Sauder, Maxwell B., Keshavarzi, Sareh, Salawu, Abdulazeez, Vornicova, Olga, Butler, Marcus O., Bedard, Philippe L., Razak, Albiruni R. Abdul, Rottapel, Robert, Chruscinski, Andrzej, Coburn, Bryan, and Spreafico, Anna

Published
2023
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9. Impact on costs and outcomes of multi-gene panel testing for advanced solid malignancies: a cost-consequence analysis using linked administrative data

Author

Hernando-Calvo, Alberto, Nguyen, Paul, Bedard, Philippe L., Chan, Kelvin K.W., Saleh, Ramy R., Weymann, Deirdre, Yu, Celeste, Amir, Eitan, Regier, Dean A., Gyawali, Bishal, Kain, Danielle, Wilson, Brooke, Earle, Craig C., Mittmann, Nicole, Abdul Razak, Albiruni R., Isaranuwatchai, Wanrudee, Sabatini, Peter, Spreafico, Anna, Stockley, Tracy L., Pugh, Trevor J., Williams, Christine, Siu, Lillian L., and Hanna, Timothy P.

Published
2024
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10. First-in-human study of naporafenib (LXH254) with or without spartalizumab in adult patients with advanced solid tumors harboring MAPK signaling pathway alterations

Author

Janku, Filip, Kim, Tae Min, Iyer, Gopakumar, Spreafico, Anna, Elez, Elena, de Jonge, Maja, Yamamoto, Noboru, van der Wekken, Anthonie J., Ascierto, Paolo Antonio, Maur, Michela, Marmé, Frederik, Kiladjian, Jean-Jacques, Basu, Sumit, Baffert, Fabienne, Buigues, Amparo, Chen, Chi, Cooke, Vesselina, Giorgetti, Elisa, Kim, Jaeyeon, McCarthy, Fiona, Moschetta, Michele, and Dummer, Reinhard

Published
2024
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13. Pre-encoded responsiveness to type I interferon in the peripheral immune system defines outcome of PD1 blockade therapy

Author

Boukhaled, Giselle M., Gadalla, Ramy, Elsaesser, Heidi J., Abd-Rabbo, Diala, Quevedo, Rene, Yang, S. Y. Cindy, Guo, Mengdi, Wang, Ben X., Noamani, Babak, Gray, Diana, Lau, Sally C. M., Taylor, Kirsty, Aung, Kyaw, Spreafico, Anna, Hansen, Aaron R., Saibil, Samuel D., Hirano, Naoto, Guidos, Cynthia, Pugh, Trevor J., McGaha, Tracy L., Ohashi, Pamela S., Sacher, Adrian G., Butler, Marcus O., and Brooks, David G.

Published
2022
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16. Phase I pharmacokinetic study of single agent trametinib in patients with advanced cancer and hepatic dysfunction

Author

Voon, Pei Jye, Chen, Eric X., Chen, Helen X., Lockhart, Albert C., Sahebjam, Solmaz, Kelly, Karen, Vaishampayan, Ulka N., Subbiah, Vivek, Razak, Albiruni R., Renouf, Daniel J., Hotte, Sebastien J., Singh, Arti, Bedard, Philippe L., Hansen, Aaron R., Ivy, S. Percy, Wang, Lisa, Stayner, Lee-Anne, Siu, Lillian L., and Spreafico, Anna

Published
2022
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17. Nodal Metastases in Stage 3 Head and Neck Melanoma: Patterns of Metastases and Patterns of Failure.

Author

Tzelnick, Sharon, de Almeida, John R., Yao, Christopher M.K.L., Kibel, Seth, Kuehne, Nathan, Grewal, Rajan, Butler, Marcus O, Saibil, Sam, Spreafico, Anna, Easson, Alexandra, and Goldstein, David P

Abstract

Objective: Stage 3 patients with clinically positive nodal metastasis are treated with therapeutic neck dissection and adjuvant systemic therapy. The aim of our study was to examined the predictability of pre‐operative CT as a nodal drainage assessment tool. Methods: Retrospective review of all patients with clinically positive head and neck cutaneous melanoma between 2010 and 2019. Clinical disease was diagnosed as radiological suspicious, biopsy‐proven node. A pre‐operative CT evaluation for nodal metastasis was compared to pathology report. Results: A total of 53 patients were included. Forty patients (75.5%) were males with a mean age of 59 (SD 15.52). The majority of patients (26.4%) had an unknown primary site. The most common sites for primary were the cheek in eight patients (15.1%) followed by forehead (9.4%) and lateral neck (9.4%). Preoperative CT predicted nodal disease in 84.6% of cases. The primary region that mainly failed from the previously described clinical prediction was the upper anterior neck with 83.3% parotid involvement. A total of 10 patients (18.9%) were diagnosis with non‐clinical nodes on pathology with a median non‐clinical node of 1 (range 1–2). Of them, 9 (90%) were in the same clinical levels detected by CT. Pre‐operative CT was associated with a neck level accuracy of 98.1%. Conclusion: Stage 3 head and neck melanoma with clinically positive nodal metastasis that are eligible for an adjuvant systemic treatment, may benefit from a highly selective neck dissection according to their pre‐operative imaging studies. This should be further evaluated in a large‐scale clinical trial. Level of Evidence: 3 Laryngoscope, 134:4292–4297, 2024 [ABSTRACT FROM AUTHOR]

Published
2024
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18. Pembrolizumab Plus Carboplatin and Paclitaxel as First-Line Therapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-B10): A Single-Arm Phase IV Trial.

Author

Dzienis, Marcin, Cundom, Juan, Fuentes, Christian Sebastian, Spreafico, Anna, Nordlinger, Melanie, Pastor, Andrea Viviana, Alesi, Erin, Neki, Anterpreet, Fung, Andrea S., Figueiredo Lima, Iane Pinto, Oppelt, Peter, da Cunha Junior, Geraldo Felicio, Burtness, Barbara, Franke, Fabio Andre, Tseng, Jennifer E., Joshi, Abhishek, McCarthy, Joy, Swaby, Ramona, Sidi, Yulia, and Gumuscu, Burak

Published
2024
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20. Early Changes in Tumor-Naive Cell-Free Methylomes and Fragmentomes Predict Outcomes in Pembrolizumab-Treated Solid Tumors

Author

Stutheit-Zhao, Eric Y., primary, Sanz-Garcia, Enrique, additional, Liu, Zhihui (Amy), additional, Wong, Derek, additional, Marsh, Kayla, additional, Abdul Razak, Albiruni R., additional, Spreafico, Anna, additional, Bedard, Philippe L., additional, Hansen, Aaron R., additional, Lheureux, Stephanie, additional, Torti, Dax, additional, Lam, Bernard, additional, Yang, Shih Yu Cindy, additional, Burgener, Justin, additional, Luo, Ping, additional, Zeng, Yong, additional, Cheng, Nicholas, additional, Awadalla, Philip, additional, Bratman, Scott V., additional, Ohashi, Pamela S., additional, Pugh, Trevor J., additional, and Siu, Lillian L., additional

Published
2024
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23. Prognostic value of clinical and radiologic extranodal extension and their role in the 8th edition TNM cN classification for HPV-negative oropharyngeal carcinoma

Author

Pilar, Avinash, Yu, Eugene, Su, Jie, O'Sullivan, Brian, Bartlett, Eric, Waldron, John N., Ringash, Jolie, Spreafico, Anna, Hansen, Aaron R., de Almeida, John, Bayley, Andrew, Bratman, Scott V., Cho, John, Giuliani, Meredith, Hope, Andrew, Hosni, Ali, Kim, John, Tong, Li, Xu, Wei, and Huang, Shao Hui

Published
2021
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24. A Phase Ib Dose-Escalation Study of Encorafenib and Cetuximab with or without Alpelisib in Metastatic BRAF-Mutant Colorectal Cancer

Author

van Geel, Robin MJM, Tabernero, Josep, Elez, Elena, Bendell, Johanna C, Spreafico, Anna, Schuler, Martin, Yoshino, Takayuki, Delord, Jean-Pierre, Yamada, Yasuhide, Lolkema, Martijn P, Faris, Jason E, Eskens, Ferry ALM, Sharma, Sunil, Yaeger, Rona, Lenz, Heinz-Josef, Wainberg, Zev A, Avsar, Emin, Chatterjee, Arkendu, Jaeger, Savina, Tan, Eugene, Maharry, Kati, Demuth, Tim, and Schellens, Jan HM

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Digestive Diseases, Clinical Research, Cancer, Colo-Rectal Cancer, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Carbamates, Cetuximab, Colorectal Neoplasms, Disease-Free Survival, Female, Humans, Male, Maximum Tolerated Dose, Middle Aged, Mutation, Phosphoinositide-3 Kinase Inhibitors, Protein Kinase Inhibitors, Proto-Oncogene Proteins B-raf, Sulfonamides, Thiazoles, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Preclinical evidence suggests that concomitant BRAF and EGFR inhibition leads to sustained suppression of MAPK signaling and suppressed tumor growth in BRAFV600E colorectal cancer models. Patients with refractory BRAFV600-mutant metastatic CRC (mCRC) were treated with a selective RAF kinase inhibitor (encorafenib) plus a monoclonal antibody targeting EGFR (cetuximab), with (n = 28) or without (n = 26) a PI3Kα inhibitor (alpelisib). The primary objective was to determine the maximum tolerated dose (MTD) or a recommended phase II dose. Dose-limiting toxicities were reported in 3 patients receiving dual treatment and 2 patients receiving triple treatment. The MTD was not reached for either group and the phase II doses were selected as 200 mg encorafenib (both groups) and 300 mg alpelisib. Combinations of cetuximab and encorafenib showed promising clinical activity and tolerability in patients with BRAF-mutant mCRC; confirmed overall response rates of 19% and 18% were observed and median progression-free survival was 3.7 and 4.2 months for the dual- and triple-therapy groups, respectively.Significance: Herein, we demonstrate that dual- (encorafenib plus cetuximab) and triple- (encorafenib plus cetuximab and alpelisib) combination treatments are tolerable and provide promising clinical activity in the difficult-to-treat patient population with BRAF-mutant mCRC. Cancer Discov; 7(6); 610-9. ©2017 AACR.See related commentary by Sundar et al., p. 558This article is highlighted in the In This Issue feature, p. 539.

Published
2017

25. Phase 1, first-in-human study of TYRP1-TCB (RO7293583), a novel TYRP1-targeting CD3 T-cell engager, in metastatic melanoma: active drug monitoring to assess the impact of immune response on drug exposure

Author

Spreafico, Anna; https://orcid.org/0000-0002-3034-3042, Couselo, Eva Muñoz, Irmisch, Anja; https://orcid.org/0000-0001-9820-1844, Bessa, Juliana, Au-Yeung, George, Bechter, Oliver, Svane, Inge Marie, Sanmamed, Miguel F; https://orcid.org/0000-0002-7295-6074, Gambardella, Valentina, McKean, Meredith; https://orcid.org/0000-0003-0944-7418, Callahan, Margaret, Dummer, Reinhard; https://orcid.org/0000-0002-2279-6906, Klein, Christian; https://orcid.org/0000-0001-7594-7280, Umaña, Pablo, Justies, Nicole, Heil, Florian, Fahrni, Linda, Opolka-Hoffmann, Eugenia, Waldhauer, Inja, Bleul, Conrad, Staack, Roland F, Karanikas, Vaios, Fowler, Stephen, Spreafico, Anna; https://orcid.org/0000-0002-3034-3042, Couselo, Eva Muñoz, Irmisch, Anja; https://orcid.org/0000-0001-9820-1844, Bessa, Juliana, Au-Yeung, George, Bechter, Oliver, Svane, Inge Marie, Sanmamed, Miguel F; https://orcid.org/0000-0002-7295-6074, Gambardella, Valentina, McKean, Meredith; https://orcid.org/0000-0003-0944-7418, Callahan, Margaret, Dummer, Reinhard; https://orcid.org/0000-0002-2279-6906, Klein, Christian; https://orcid.org/0000-0001-7594-7280, Umaña, Pablo, Justies, Nicole, Heil, Florian, Fahrni, Linda, Opolka-Hoffmann, Eugenia, Waldhauer, Inja, Bleul, Conrad, Staack, Roland F, Karanikas, Vaios, and Fowler, Stephen

Abstract

Introduction: Although checkpoint inhibitors (CPIs) have improved outcomes for patients with metastatic melanoma, those progressing on CPIs have limited therapeutic options. To address this unmet need and overcome CPI resistance mechanisms, novel immunotherapies, such as T-cell engaging agents, are being developed. The use of these agents has sometimes been limited by the immune response mounted against them in the form of anti-drug antibodies (ADAs), which is challenging to predict preclinically and can lead to neutralization of the drug and loss of efficacy. Methods: TYRP1-TCB (RO7293583; RG6232) is a T-cell engaging bispecific (TCB) antibody that targets tyrosinase-related protein 1 (TYRP1), which is expressed in many melanomas, thereby directing T cells to kill TYRP1-expressing tumor cells. Preclinical studies show TYRP1-TCB to have potent anti-tumor activity. This first-in-human (FIH) phase 1 dose-escalation study characterized the safety, tolerability, maximum tolerated dose/optimal biological dose, and pharmacokinetics (PK) of TYRP1-TCB in patients with metastatic melanoma (NCT04551352). Results: Twenty participants with cutaneous, uveal, or mucosal TYRP1-positive melanoma received TYRP1-TCB in escalating doses (0.045 to 0.4 mg). All participants experienced ≥1 treatment-related adverse event (TRAE); two participants experienced grade 3 TRAEs. The most common toxicities were grade 1–2 cytokine release syndrome (CRS) and rash. Fractionated dosing mitigated CRS and was associated with lower levels of interleukin-6 and tumor necrosis factor-alpha. Measurement of active drug (dual TYPR1- and CD3-binding) PK rapidly identified loss of active drug exposure in all participants treated with 0.4 mg in a flat dosing schedule for ≥3 cycles. Loss of exposure was associated with development of ADAs towards both the TYRP1 and CD3 domains. A total drug PK assay, measuring free and ADA-bound forms, demonstrated that TYRP1-TCB-ADA immune complexes were present in participant

Published
2024

26. Transitions in oral and gut microbiome of HPV+ oropharyngeal squamous cell carcinoma following definitive chemoradiotherapy (ROMA LA-OPSCC study)

Author

Oliva, Marc, Schneeberger, Pierre H. H., Rey, Victor, Cho, Matthew, Taylor, Rachel, Hansen, Aaron R., Taylor, Kirsty, Hosni, Ali, Bayley, Andrew, Hope, Andrew J., Bratman, Scott V., Ringash, Jolie, Singh, Simron, Weinreb, Ilan, Perez-Ordoñez, Bayardo, Chepeha, Douglas, Waldron, John, Xu, Wei, Guttman, David, Siu, Lillian L., Coburn, Bryan, and Spreafico, Anna

Published
2021
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27. Combined Transcriptome and Circulating Tumor DNA Longitudinal Biomarker Analysis Associates With Clinical Outcomes in Advanced Solid Tumors Treated With Pembrolizumab.

Author

Hernando-Calvo, Alberto, Yang, S.Y. Cindy, Vila-Casadesús, Maria, Han, Ming, Liu, Zhihui Amy, Berman, A Hal K., Spreafico, Anna, Razak, Albiruni Abdul, Lheureux, Stephanie, Hansen, Aaron R., Lo Giacco, Deborah, Abbas-Aghababazadeh, Farnoosh, Matito, Judith, Haibe-Kains, Benjamin, Pugh, Trevor J., Bratman, Scott V., Aleshin, Alexey, Berche, Roger, Saavedra, Omar, and Garralda, Elena

Subjects
CIRCULATING tumor DNA, GENE expression, HEAD & neck cancer, RNA sequencing, OVERALL survival
Abstract

PURPOSE: Immune gene expression signatures are emerging as potential biomarkers for immunotherapy (IO). VIGex is a 12-gene expression classifier developed in both nCounter (Nanostring) and RNA sequencing (RNA-seq) assays and analytically validated across laboratories. VIGex classifies tumor samples into hot, intermediate-cold (I-Cold), and cold subgroups. VIGex-Hot has been associated with better IO treatment outcomes. Here, we investigated the performance of VIGex and other IO biomarkers in an independent data set of patients treated with pembrolizumab in the INSPIRE phase II clinical trial (ClinicalTrials.gov identifier: NCT02644369). MATERIALS AND METHODS: Patients with advanced solid tumors were treated with pembrolizumab 200 mg IV once every 3 weeks. Tumor RNA-seq data from baseline tumor samples were classified by the VIGex algorithm. Circulating tumor DNA (ctDNA) was measured at baseline and start of cycle 3 using the bespoke Signatera assay. VIGex-Hot was compared with VIGex I-Cold + Cold and four groups were defined on the basis of the combination of VIGex subgroups and the change in ctDNA at cycle 3 from baseline (ΔctDNA). RESULTS: Seventy-six patients were enrolled, including 16 ovarian, 12 breast, 12 head and neck cancers, 10 melanoma, and 26 other tumor types. Objective response rate was 24% in VIGex-Hot and 10% in I-Cold/Cold. VIGex-Hot subgroup was associated with higher overall survival (OS) and progression-free survival (PFS) when included in a multivariable model adjusted for tumor type, tumor mutation burden, and PD-L1 immunohistochemistry. The addition of ΔctDNA improved the predictive performance of the baseline VIGex classification for both OS and PFS. CONCLUSION: Our data indicate that the addition of ΔctDNA to baseline VIGex may refine prediction for IO. Combined transcriptome and ctDNA longitudinal analysis associates with pembrolizumab outcomes. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Clinical Predictors of Cisplatin Chemoradiation-Induced Ototoxicity in HPV-Positive Oropharyngeal Squamous Cell Carcinoma: A Case-Control Study.

Author

Lee, John JW., Alamleh, Salahaldin, Zhan, Luna Jia, Hueniken, Katrina, Mahler, Mary B., Billfalk-Kelly, Astrid, Davies, Joel, Brown, M. Catherine, Spreafico, Anna, Huang, Shao Hui, Hope, Andrew, Xu, Wei, Goldstein, David P., and Liu, Geoffrey

Subjects
PAPILLOMAVIRUS diseases, SQUAMOUS cell carcinoma, RISK assessment, CISPLATIN, RESEARCH funding, OROPHARYNGEAL cancer, MULTIPLE regression analysis, CHEMORADIOTHERAPY, RETROSPECTIVE studies, AUDIOMETRY, DESCRIPTIVE statistics, ODDS ratio, CASE-control method, OTOTOXICITY, CONFIDENCE intervals, COMPARATIVE studies, PATIENT aftercare, DISEASE risk factors
Abstract

Background: Cisplatin-based chemoradiation is a standard treatment for many patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), an etiologically distinct subset of head and neck cancer. Although associated with good long-term survival, clinical risk factors for ototoxicity have been understudied in this population. This study aimed to evaluate clinical predictors associated with ototoxicity in HPV-positive OPSCC patients treated with cisplatin chemoradiation. Methods: This retrospective case-control study included 201 adult patients (>18 years) with histologically confirmed HPV-positive OPSCC who received cisplatin chemoradiation as their primary treatment from 2001 and 2019 at a single tertiary cancer center. Ototoxicity was determined using baseline and follow-up audiometry and the Common Terminology Criteria for Adverse Events v5.0 grading criteria (Grade ≥2). Multivariable logistic regression [adjusted odds ratio (aOR)] identified significant predictors that increased the odds of ototoxicity. Results: A total of 201 patients [165 males; median (IQR) age, 57 (11) years] were included in the study. The incidence of ototoxicity in the worst ear was 56.2%, with the greatest hearing loss occurring at high frequencies (4-8 kHz), resulting in a loss of 12.5 dB at 4 to 6 kHz and 20 dB at 6 to 8 kHz. High-dose cisplatin administration compared to weekly administration [aOR 4.93 (95% CI: 1.84-14.99), P =.003], a higher mean cochlear radiation dose [aOR 1.58 (95% CI: 1.12-2.30), P =.01], smoking history [aOR 2.89 (95% CI: 1.51-5.63), P =.001], and a 10 year increase in age [aOR 2.07 (95% CI: 1.25-3.52), P =.006] were each independently associated with increased odds of ototoxicity. Conclusions: Clinical predictors of ototoxicity in HPV-positive OPSCC patients treated with cisplatin-based chemoradiation include the use of a high-dose cisplatin regimen, higher cochlear radiation doses, a history of smoking, and older age. With the rising incidence of this malignancy in Western countries and overall improved survivorship, our research motivates future studies into risk stratification and earlier interventions to mitigate and reduce the risk of ototoxicity. [ABSTRACT FROM AUTHOR]

Published
2024
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29. Baseline biomarkers of efficacy and on-treatment immune-profile changes associated with bempegaldesleukin plus nivolumab.

Author

Gogas, Helen, Ravimohan, Shruthi, Datta, Antara, Chhibber, Aparna, Couselo, Eva Muñoz, Diab, Adi, Pereira, Caio, Quéreux, Gaëlle, Sandhu, Shahneen, Curti, Brendan, Khushalani, Nikhil I., Taylor, Matthew H., Daniels, Gregory A., Spreafico, Anna, Meniawy, Tarek, Van Den Eertwegh, Alfons J. M., Sun, Yongliang, Arriaga, Yull, Zhou, Ming, and Long, Georgina V.

Subjects
REGULATORY T cells, TUMOR markers, NIVOLUMAB, BIOMARKERS, T cells
Abstract

In PIVOT IO 001 (NCT03635983), the combination of the investigational interleukin-2 agonist bempegaldesleukin (BEMPEG) with nivolumab (NIVO) had no added clinical benefit over NIVO monotherapy in unresectable/metastatic melanoma. Pre-defined baseline and on-treatment changes in selected biomarkers were analyzed to explore the potential mechanisms underlying the clinical observations. In each treatment arm, higher baseline tumor mutational burden or immune infiltration/inflammation was associated with improved efficacy compared with lower levels. On-treatment peripheral biomarker changes showed that BEMPEG + NIVO increased all immune cell subset counts interrogated, including regulatory T cells. This was followed by attenuation of the increase in CD8 + T cells, conventional CD4 + T cells, and systemic interferon gamma levels at later treatment cycles in the combination arm. Changes in tumor biomarkers were comparable between arms. These biomarker results help provide a better understanding of the mechanism of action of BEMPEG + NIVO and may help contextualize the clinical observations from PIVOT IO 001. [ABSTRACT FROM AUTHOR]

Published
2024
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30. Treatment implications of postoperative chemoradiotherapy for squamous cell carcinoma of the oral cavity with minor and major extranodal extension

Author

de Almeida, John R., Truong, Tra, Khan, Nazir Mohemmed, Su, Jie Susie, Irish, Jonathan, Gilbert, Ralph, Goldstein, David, Huang, Shao Hui, O'Sullivan, Brian, Hosni, Ali, Hope, Andrew, Waldron, John, Hansen, Aaron R., Spreafico, Anna, Siu, Lillian L., Perez-Ordonez, Bayardo, Xu, Wei, and Weinreb, Ilan

Published
2020
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31. Impact of cumulative cisplatin dose and adjuvant chemotherapy in locally-advanced nasopharyngeal carcinoma treated with definitive chemoradiotherapy

Author

Oliva, Marc, Huang, Shao Hui, Taylor, Rachel, Su, Jie, Xu, Wei, Hansen, Aaron R, Jang, Raymond, Bayley, Andrew, Hosni, Ali, Giuliani, Meredith, Ringash, Jolie, Bratman, Scott V, Cho, John, Irish, Jonathan, Waldron, John, Weinreb, Ilan, Kim, John, O'Sullivan, Brian, Siu, Lillian L, and Spreafico, Anna

Published
2020
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32. Clinical Activity of Mitogen-Activated Protein Kinase–Targeted Therapies in Patients With Non–V600 BRAF-Mutant Tumors

Author

Dankner, Matthew, Wang, Yifan, Fazelzad, Rouhi, Johnson, Benny, Nebhan, Caroline A., Dagogo-Jack, Ibiayi, Myall, Nathaniel J., Richtig, Georg, Bracht, Jillian W.P., Gerlinger, Marco, Shinozaki, Eiji, Yoshino, Takayuki, Kotani, Daisuke, Fangusaro, Jason R., Gautschi, Oliver, Mazieres, Julien, Sosman, Jeffrey A., Kopetz, Scott, Subbiah, Vivek, Davies, Michael A., Groover, Anna L., Sullivan, Ryan J., Flaherty, Keith T., Johnson, Douglas B., Benedetti, Andrea, Cescon, David W., Spreafico, Anna, Zogopoulos, George, and Rose, April A.N.

Published
2022
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35. Pan-cancer analysis of longitudinal metastatic tumors reveals genomic alterations and immune landscape dynamics associated with pembrolizumab sensitivity

Author

Cindy Yang, S. Y., Lien, Scott C., Wang, Ben X., Clouthier, Derek L., Hanna, Youstina, Cirlan, Iulia, Zhu, Kelsey, Bruce, Jeffrey P., El Ghamrasni, Samah, Iafolla, Marco A. J., Oliva, Marc, Hansen, Aaron R., Spreafico, Anna, Bedard, Philippe L., Lheureux, Stephanie, Razak, Albiruni, Speers, Vanessa, Berman, Hal K., Aleshin, Alexey, Haibe-Kains, Benjamin, Brooks, David G., McGaha, Tracy L., Butler, Marcus O., Bratman, Scott V., Ohashi, Pamela S., Siu, Lillian L., and Pugh, Trevor J.

Published
2021
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36. Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab

Author

Bratman, Scott V., Yang, S. Y. Cindy, Iafolla, Marco A. J., Liu, Zhihui, Hansen, Aaron R., Bedard, Philippe L., Lheureux, Stephanie, Spreafico, Anna, Razak, Albiruni Abdul, Shchegrova, Svetlana, Louie, Maggie, Billings, Paul, Zimmermann, Bernhard, Sethi, Himanshu, Aleshin, Alexey, Torti, Dax, Marsh, Kayla, Eagles, Jenna, Cirlan, Iulia, Hanna, Youstina, Clouthier, Derek L., Lien, Scott C., Ohashi, Pamela S., Xu, Wei, Siu, Lillian L., and Pugh, Trevor J.

Published
2020
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38. Validation of distant metastases risk-groups in oral cavity squamous cell carcinoma patients treated with postoperative intensity-modulated radiotherapy

Author

Hosni, Ali, Huang, Shao Hui, Chiu, Kevin, Xu, Wei, Su, Jie, Lu, Lin, Bayley, Andrew, Bratman, Scott V., Cho, John, Giuliani, Meredith, Kim, John, O'Sullivan, Brian, Ringash, Jolie, Waldron, John, Spreafico, Anna, de Almeida, John R., Chepeha, Douglas B., Irish, Jonathan C., Goldstein, David P., and Hope, Andrew

Published
2019
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39. Predictors of Early Recurrence Prior to Planned Postoperative Radiation Therapy for Oral Cavity Squamous Cell Carcinoma and Outcomes Following Salvage Intensified Radiation Therapy

Author

Hosni, Ali, Huang, Shao Hui, Chiu, Kevin, Xu, Wei, Su, Jie, Bayley, Andrew, Bratman, Scott V., Cho, John, Giuliani, Meredith, Kim, John, O'Sullivan, Brian, Ringash, Jolie, Waldron, John, Spreafico, Anna, Yu, Eugene, de Almeida, John R., Monteiro, Eric, Chepeha, Douglas B., Irish, Jonathan C., Goldstein, David P., and Hope, Andrew

Published
2019
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40. Phase 1, first-in-human study of TYRP1-TCB (RO7293583), a novel TYRP1-targeting CD3 T-cell engager, in metastatic melanoma: active drug monitoring to assess the impact of immune response on drug exposure.

Author

Spreafico, Anna, Couselo, Eva Muñoz, Irmisch, Anja, Bessa, Juliana, Au-Yeung, George, Bechter, Oliver, Svane, Inge Marie, Sanmamed, Miguel F., Gambardella, Valentina, McKean, Meredith, Callahan, Margaret, Dummer, Reinhard, Klein, Christian, Umaña, Pablo, Justies, Nicole, Heil, Florian, Fahrni, Linda, Opolka-Hoffmann, Eugenia, Waldhauer, Inja, and Bleul, Conrad

Subjects
MICROPHTHALMIA-associated transcription factor, DRUG monitoring, IMMUNE response, TUMOR necrosis factors, CYTOKINE release syndrome, T cells, UVEA cancer, UVEAL diseases
Abstract

Introduction: Although checkpoint inhibitors (CPIs) have improved outcomes for patients with metastatic melanoma, those progressing on CPIs have limited therapeutic options. To address this unmet need and overcome CPI resistance mechanisms, novel immunotherapies, such as T-cell engaging agents, are being developed. The use of these agents has sometimes been limited by the immune response mounted against them in the form of anti-drug antibodies (ADAs), which is challenging to predict preclinically and can lead to neutralization of the drug and loss of efficacy. Methods: TYRP1-TCB (RO7293583; RG6232) is a T-cell engaging bispecific (TCB) antibody that targets tyrosinase-related protein 1 (TYRP1), which is expressed in many melanomas, thereby directing T cells to kill TYRP1-expressing tumor cells. Preclinical studies show TYRP1-TCB to have potent anti-tumor activity. This first-in-human (FIH) phase 1 dose-escalation study characterized the safety, tolerability, maximum tolerated dose/optimal biological dose, and pharmacokinetics (PK) of TYRP1-TCB in patients with metastatic melanoma (NCT04551352). Results: Twenty participants with cutaneous, uveal, or mucosal TYRP1-positive melanoma received TYRP1-TCB in escalating doses (0.045 to 0.4 mg). All participants experienced ≥1 treatment-related adverse event (TRAE); two participants experienced grade 3 TRAEs. The most common toxicities were grade 1-2 cytokine release syndrome (CRS) and rash. Fractionated dosing mitigated CRS and was associated with lower levels of interleukin-6 and tumor necrosis factor-alpha. Measurement of active drug (dual TYPR1- and CD3-binding) PK rapidly identified loss of active drug exposure in all participants treated with 0.4 mg in a flat dosing schedule for ≥3 cycles. Loss of exposure was associated with development of ADAs towards both the TYRP1 and CD3 domains. A total drug PK assay, measuring free and ADA-bound forms, demonstrated that TYRP1-TCB-ADA immune complexes were present in participant samples, but showed no drug activity in vitro. Discussion: This study provides important insights into how the use of active drug PK assays, coupled with mechanistic follow-up, can inform and enable ongoing benefit/risk assessment for individuals participating in FIH dose-escalation trials. Translational studies that lead to a better understanding of the underlying biology of cognate T- and B-cell interactions, ultimately resulting in ADA development to novel biotherapeutics, are needed. [ABSTRACT FROM AUTHOR]

Published
2024
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41. Phase I/Ib, open-label, multicenter, dose-escalation study of the anti-TGF-β monoclonal antibody, NIS793, in combination with spartalizumab in adult patients with advanced tumors

Author

Bauer, Todd M, primary, Santoro, Armando, additional, Lin, Chia-Chi, additional, Garrido-Laguna, Ignacio, additional, Joerger, Markus, additional, Greil, Richard, additional, Spreafico, Anna, additional, Yau, Thomas, additional, Goebeler, Maria-Elisabeth, additional, Hütter-Krönke, Marie Luise, additional, Perotti, Antonella, additional, Juif, Pierre-Eric, additional, Lu, Darlene, additional, Barys, Louise, additional, Cremasco, Viviana, additional, Pelletier, Marc, additional, Evans, Helen, additional, Fabre, Claire, additional, and Doi, Toshikiko, additional

Published
2023
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43. Supplementary Table S3 from Safety, Immunologic, and Clinical Activity of Durvalumab in Combination with Olaparib or Cediranib in Advanced Leiomyosarcoma: Results of the DAPPER Clinical Trial.

Author

Salawu, Abdulazeez, primary, Wang, Ben X., primary, Han, Ming, primary, Geady, Caryn, primary, Heirali, Alya, primary, Berman, Hal K., primary, Pfister, Thomas D., primary, Hernando-Calvo, Alberto, primary, Al-Ezzi, Esmail Mutahar, primary, Stayner, Lee-Anne, primary, Gupta, Abha A., primary, Ayodele, Olubukola, primary, Lam, Bernard, primary, Hansen, Aaron R., primary, Spreafico, Anna, primary, Bedard, Philippe L., primary, Butler, Marcus O., primary, Avery, Lisa, primary, Coburn, Bryan, primary, Haibe-Kains, Benjamin, primary, Siu, Lillian L., primary, and Abdul Razak, Albiruni R., primary

Published
2023
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44. Data from Safety, Immunologic, and Clinical Activity of Durvalumab in Combination with Olaparib or Cediranib in Advanced Leiomyosarcoma: Results of the DAPPER Clinical Trial.

Author

Salawu, Abdulazeez, primary, Wang, Ben X., primary, Han, Ming, primary, Geady, Caryn, primary, Heirali, Alya, primary, Berman, Hal K., primary, Pfister, Thomas D., primary, Hernando-Calvo, Alberto, primary, Al-Ezzi, Esmail Mutahar, primary, Stayner, Lee-Anne, primary, Gupta, Abha A., primary, Ayodele, Olubukola, primary, Lam, Bernard, primary, Hansen, Aaron R., primary, Spreafico, Anna, primary, Bedard, Philippe L., primary, Butler, Marcus O., primary, Avery, Lisa, primary, Coburn, Bryan, primary, Haibe-Kains, Benjamin, primary, Siu, Lillian L., primary, and Abdul Razak, Albiruni R., primary

Published
2023
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45. Supplementary Figure S1 from Safety, Immunologic, and Clinical Activity of Durvalumab in Combination with Olaparib or Cediranib in Advanced Leiomyosarcoma: Results of the DAPPER Clinical Trial.

Author

Salawu, Abdulazeez, primary, Wang, Ben X., primary, Han, Ming, primary, Geady, Caryn, primary, Heirali, Alya, primary, Berman, Hal K., primary, Pfister, Thomas D., primary, Hernando-Calvo, Alberto, primary, Al-Ezzi, Esmail Mutahar, primary, Stayner, Lee-Anne, primary, Gupta, Abha A., primary, Ayodele, Olubukola, primary, Lam, Bernard, primary, Hansen, Aaron R., primary, Spreafico, Anna, primary, Bedard, Philippe L., primary, Butler, Marcus O., primary, Avery, Lisa, primary, Coburn, Bryan, primary, Haibe-Kains, Benjamin, primary, Siu, Lillian L., primary, and Abdul Razak, Albiruni R., primary

Published
2023
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46. Supplementary Methods S1 from Safety, Immunologic, and Clinical Activity of Durvalumab in Combination with Olaparib or Cediranib in Advanced Leiomyosarcoma: Results of the DAPPER Clinical Trial.

Author

Salawu, Abdulazeez, primary, Wang, Ben X., primary, Han, Ming, primary, Geady, Caryn, primary, Heirali, Alya, primary, Berman, Hal K., primary, Pfister, Thomas D., primary, Hernando-Calvo, Alberto, primary, Al-Ezzi, Esmail Mutahar, primary, Stayner, Lee-Anne, primary, Gupta, Abha A., primary, Ayodele, Olubukola, primary, Lam, Bernard, primary, Hansen, Aaron R., primary, Spreafico, Anna, primary, Bedard, Philippe L., primary, Butler, Marcus O., primary, Avery, Lisa, primary, Coburn, Bryan, primary, Haibe-Kains, Benjamin, primary, Siu, Lillian L., primary, and Abdul Razak, Albiruni R., primary

Published
2023
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47. Selinexor for the treatment of recurrent or metastatic salivary gland tumors: Results from the GEMS‐001 clinical trial

Author

Hernando‐Calvo, Alberto, primary, Malone, Eoghan, additional, Day, Daphne, additional, Prawira, Amy, additional, Weinreb, Ilan, additional, Yang, S. Y. Cindy, additional, Wong, Horace, additional, Rodriguez, Angela, additional, Jennings, Sarah, additional, Eliason, Anneli, additional, Wang, Lisa, additional, Spreafico, Anna, additional, Siu, Lillian L., additional, and Hansen, Aaron R., additional

Published
2023
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49. Supplementary Figure 1 from Phase 1 Study of JNJ-64619178, a Protein Arginine Methyltransferase 5 Inhibitor, in Advanced Solid Tumors

Author

Vieito, Maria, primary, Moreno, Victor, primary, Spreafico, Anna, primary, Brana, Irene, primary, Wang, Judy S., primary, Preis, Meir, primary, Hernández, Tatiana, primary, Genta, Sofia, primary, Hansen, Aaron R., primary, Doger, Bernard, primary, Galvao, Vladimir, primary, Lenox, Laurie, primary, Brown, Regina J., primary, Kalota, Anna, primary, Mehta, Jaydeep, primary, Pastore, Friederike, primary, Patel, Bharvin, primary, Mistry, Pankaj, primary, Gu, Junchen, primary, Lauring, Josh, primary, and Patel, Manish R., primary

Published
2023
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50. Abstract PO-008: Association of plasma Epstein-Barr virus DNA and clinical response in patients with recurrent and/or metastatic nasopharyngeal cancer treated with pembrolizumab or standard-of-care chemotherapy in KEYNOTE-122

Author

Chan, Anthony T. C., primary, Lee, Victor Ho Fun, additional, Hong, Ruey-Long, additional, Ahn, Myung-Ju, additional, Chong, Wan Qin, additional, Spreafico, Anna, additional, Kim, Sung-Bae, additional, Ho, Gwo Fuang, additional, Caguioa, Priscilla B., additional, Ngamphaiboon, Nuttapong, additional, Swaby, Ramona F., additional, Wei, Bo, additional, Webber, Andrea, additional, Kang, John, additional, Gumuscu, Burak, additional, Yuan, Jianda, additional, and Siu, Lillian, additional

Published
2023
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