Search

Your search keyword '"Cobimetinib"' showing total 24 results
Start Over Descriptor "Cobimetinib" Journal annals of oncology
24 results on '"Cobimetinib"'

1. Biomarkers of treatment benefit with atezolizumab plus vemurafenib plus cobimetinib in BRAFV600 mutation–positive melanoma.

Author

Robert, C., Lewis, K.D., Gutzmer, R., Stroyakovskiy, D., Gogas, H., Protsenko, S., Pereira, R.P., Eigentler, T., Rutkowski, P., Demidov, L., Caro, I., Forbes, H., Shah, K., Yan, Y., Li, H., McArthur, G.A., and Ascierto, P.A.

Subjects
*PROGRAMMED cell death 1 receptors, *ATEZOLIZUMAB, *VEMURAFENIB, *PROGRAMMED death-ligand 1, *RECURSIVE partitioning, *MELANOMA, *BIOMARKERS
Abstract

The phase III IMspire150 study (NCT02908672) demonstrated significantly improved progression-free survival (PFS) with atezolizumab, vemurafenib, and cobimetinib (atezolizumab group) versus placebo, vemurafenib, and cobimetinib (control group) in patients with BRAF V600-mutated advanced melanoma. We report exploratory biomarker analyses to optimize targeting of patients who are more likely to benefit from triplet combination therapy. Five hundred fourteen patients were randomized to atezolizumab (n = 256) or control (n = 258). Outcomes were evaluated in subgroups defined by key biomarkers, including programmed death-ligand 1 (PD-L1) expression, lactate dehydrogenase (LDH) level, tumor mutational burden (TMB), and interferon-γ (IFN-γ) gene signature. Exploratory recursive partitioning analysis was then used to model associations between PFS and baseline covariates, including key biomarkers. PFS benefit for atezolizumab versus control was greater in patients with high TMB [≥10 mutations/Mb; hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.52-1.02; P = 0.067] versus low TMB (<10 mutations/Mb; HR 0.92; 95% CI 0.65-1.30; P = 0.64) and similar between patients with strong IFN-γ (≥median; HR 0.76; 95% CI 0.54-1.06) versus weak IFN-γ (

Published
2022
Full Text
View/download PDF

2. A phase II randomized trial of cobimetinib plus chemotherapy, with or without atezolizumab, as first-line treatment for patients with locally advanced or metastatic triple-negative breast cancer (COLET): primary analysis.

Author

Brufsky, A., Kim, S.B., Zvirbule, Ž., Eniu, A., Mebis, J., Sohn, J.H., Wongchenko, M., Chohan, S., Amin, R., Yan, Y., McNally, V., Miles, D., and Loi, S.

Subjects
*ANTINEOPLASTIC combined chemotherapy protocols, *CANCER chemotherapy, *METASTATIC breast cancer, *TRIPLE-negative breast cancer, *MITOGEN-activated protein kinases, *PACLITAXEL, *TAXANES, *CANCER immunotherapy
Abstract

Resistance to standard chemotherapy in metastatic triple-negative breast cancer (mTNBC) is associated with upregulation of the mitogen-activated protein kinase (MAPK) pathway. Cobimetinib, an MAPK/extracellular signal-regulated kinase (MEK) inhibitor, may increase sensitivity to taxanes and programmed death-ligand 1 inhibitors. COLET is a three-cohort phase II study evaluating first-line cobimetinib plus chemotherapy, with or without atezolizumab, in patients with locally advanced or mTNBC. Patients were ≥18 years with locally advanced or mTNBC. Following a safety run-in, patients in cohort I were randomized 1:1 to cobimetinib (60 mg, D3-D23 of each 28-day cycle) or placebo, plus paclitaxel (80 mg/m2, D1, 8, and 15). Additional patients were randomized (1:1) to cohort II or III to receive cobimetinib plus atezolizumab (840 mg, D1 and D15) and either paclitaxel (cohort II) or nab-paclitaxel [cohort III (100 mg/m2, D1, D8, and D15)]. Primary endpoints were investigator-assessed progression-free survival (PFS) (cohort I) and confirmed objective response rate (ORR) (cohorts II/III). Safety and tolerability were also assessed. In the expansion stages, median PFS was 5.5 months for cobimetinib/paclitaxel versus 3.8 months for placebo/paclitaxel in cohort I [hazard ratio 0.73; 95% confidence interval (CI) 0.43-1.24; P = 0.25]. In cohort I, ORR was 38.3% (95% CI 24.40-52.20) for cobimetinib/paclitaxel and 20.9% (95% CI 8.77-33.09) for placebo/paclitaxel; ORRs in cohorts II and III were 34.4% (95% CI 18.57-53.19) and 29.0% (95% CI 14.22-48.04), respectively. Diarrhea was the most common grade ≥3 adverse events across all cohorts. Cobimetinib added to paclitaxel did not lead to a statistically significant increase in PFS or ORR, although a nonsignificant trend toward a numerical increase was observed. Cobimetinib plus atezolizumab and a taxane did not appear to increase ORR. This demonstrates the potential activity of a combinatorial MEK inhibitor, chemotherapy, and immunotherapy in this difficult-to-treat population. • Cobimetinib plus paclitaxel trended toward a numerical increase in progression-free survival and objective response rate. • The triplet combination of atezolizumab, cobimetinib, and taxane did not appear to increase objective response rate. • The triplet combination showed a trend toward improved objective response rate in patients with programmed death-ligand 1 (PD-L1)-positive disease. • These results demonstrate the potential activity of combination immunotherapy for this difficult-to-treat patient subgroup. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

3. Cobimetinib plus atezolizumab in BRAFV600 wild-type melanoma: primary results from the randomized phase III IMspire170 study.

Author

Gogas, H., Dréno, B., Larkin, J., Demidov, L., Stroyakovskiy, D., Eroglu, Z., Francesco Ferrucci, P., Pigozzo, J., Rutkowski, P., Mackiewicz, J., Rooney, I., Voulgari, A., Troutman, S., Pitcher, B., Guo, Y., Yan, Y., Castro, M., Mulla, S., Flaherty, K., and Arance, A.

Subjects
*DRUG efficacy, *COMBINATION drug therapy, *MELANOMA, *MELANOMA prognosis, *GENETIC mutation
Abstract

Emerging data suggest that the combination of MEK inhibitors and immunotherapeutic agents may result in improved efficacy in melanoma. We evaluated whether combining MEK inhibition and immune checkpoint inhibition was more efficacious than immune checkpoint inhibition alone in patients with previously untreated BRAF V600 wild-type advanced melanoma. IMspire170 was an international, randomized, open-label, phase III study. Patients were randomized 1 : 1 to receive cobimetinib (60 mg, days 1-21) plus anti-programmed death-ligand 1 atezolizumab (840 mg every 2 weeks) in 28-day cycles or anti-programmed death-1 pembrolizumab (200 mg every 3 weeks) alone until loss of clinical benefit, unacceptable toxicity, or consent withdrawal. The primary outcome was progression-free survival (PFS), assessed by an independent review committee in the intention-to-treat population. Between 11 December 2017, and 29 January 2019, 446 patients were randomized to receive cobimetinib plus atezolizumab (n = 222) or pembrolizumab (n = 224). Median follow-up was 7.1 months [interquartile range (IQR) 4.8-9.9] for cobimetinib plus atezolizumab and 7.2 months (IQR 4.9-10.1) for pembrolizumab. Median PFS was 5.5 months [95% confidence interval (CI) 3.8-7.2] with cobimetinib plus atezolizumab versus 5.7 months (95% CI 3.7-9.6) with pembrolizumab [stratified hazard ratio 1.15 (95% CI 0.88-1.50); P = 0.30]. Hazard ratios for PFS were consistent across prespecified subgroups. In exploratory biomarker analyses, higher tumor mutational burden was associated with improved clinical outcomes in both treatment arms. The most common grade 3-5 adverse events (AEs) were increased blood creatine phosphokinase (10.0% with cobimetinib plus atezolizumab versus 0.9% with pembrolizumab), diarrhea (7.7% versus 1.9%), rash (6.8% versus 0.9%), hypertension (6.4% versus 3.7%), and dermatitis acneiform (5.0% versus 0). Serious AEs occurred in 44.1% of patients with cobimetinib plus atezolizumab and 20.8% with pembrolizumab. Cobimetinib plus atezolizumab did not improve PFS compared with pembrolizumab monotherapy in patients with BRAF V600 wild-type advanced melanoma. • Cobimetinib plus atezolizumab did not improve PFS versus pembrolizumab monotherapy in BRAF V600 wild-type advanced melanoma. • Results were consistent across prespecified subgroups according to known prognostic factors. • Higher tumor mutational burden was associated with improved clinical outcomes in both treatment arms. • As expected, the combination was associated with a higher incidence of AEs than pembrolizumab monotherapy. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

4. Phase Ib study of atezolizumab combined with cobimetinib in patients with solid tumors.

Author

Hellmann, M D, Kim, T -W, Lee, C B, Goh, B -C, Miller, W H, Oh, D -Y, Jamal, R, Chee, C -E, Chow, L Q M, Gainor, J F, Desai, J, Solomon, B J, Thakur, M Das, Pitcher, B, Foster, P, Hernandez, G, Wongchenko, M J, Cha, E, Bang, Y -J, and Siu, L L

Subjects
*RAS oncogenes, *NON-small-cell lung carcinoma, *APOPTOSIS, *MELANOMA, *PROGRESSION-free survival, *T cells, *COLON cancer
Abstract

Background Preclinical evidence suggests that MEK inhibition promotes accumulation and survival of intratumoral tumor-specific T cells and can synergize with immune checkpoint inhibition. We investigated the safety and clinical activity of combining a MEK inhibitor, cobimetinib, and a programmed cell death 1 ligand 1 (PD-L1) inhibitor, atezolizumab, in patients with solid tumors. Patients and methods This phase I/Ib study treated PD-L1/PD-1-naive patients with solid tumors in a dose-escalation stage and then in multiple, indication-specific dose-expansion cohorts. In most patients, cobimetinib was dosed once daily orally for 21 days on, 7 days off. Atezolizumab was dosed at 800 mg intravenously every 2 weeks. The primary objectives were safety and tolerability. Secondary end points included objective response rate, progression-free survival, and overall survival. Results Between 27 December 2013 and 9 May 2016, 152 patients were enrolled. As of 4 September 2017, 150 patients received ≥1 dose of atezolizumab, including 14 in the dose-escalation cohorts and 136 in the dose-expansion cohorts. Patients had metastatic colorectal cancer (mCRC; n  = 84), melanoma (n  = 22), non-small-cell lung cancer (NSCLC; n  = 28), and other solid tumors (n  = 16). The most common all-grade treatment-related adverse events (AEs) were diarrhea (67%), rash (48%), and fatigue (40%), similar to those with single-agent cobimetinib and atezolizumab. One (<1%) treatment-related grade 5 AE occurred (sepsis). Forty-five (30%) and 23 patients (15%) had AEs that led to discontinuation of cobimetinib and atezolizumab, respectively. Confirmed responses were observed in 7 of 84 patients (8%) with mCRC (6 responders were microsatellite low/stable, 1 was microsatellite instable), 9 of 22 patients (41%) with melanoma, and 5 of 28 patients (18%) with NSCLC. Clinical activity was independent of KRAS/BRAF status across diseases. Conclusions Atezolizumab plus cobimetinib had manageable safety and clinical activity irrespective of KRAS/BRAF status. Although potential synergistic activity was seen in mCRC, this was not confirmed in a subsequent phase III study. ClinicalTrials.gov Identifier NCT01988896 (the investigators in the NCT01988896 study are listed in the supplementary Appendix , available at Annals of Oncology online). [ABSTRACT FROM AUTHOR]

Published
2019
Full Text
View/download PDF

5. Incidence, course, and management of toxicities associated with cobimetinib in combination with vemurafenib in the coBRIM study.

Author

Dréno, B., Ribas, A., Larkin, J., Ascierto, P. A., Hauschild, A., Thomas, L., Grob, J.-J., Koralek, D. O., Rooney, I., Hsu, J. J., McKenna, E. F., and McArthur, G. A.

Subjects
*MELANOMA, *PLACEBOS, *NEUROENDOCRINE tumors, *PROGRESSION-free survival, *PATIENTS, *TUMOR treatment
Abstract

Background: In the coBRIM phase III trial, the addition of cobimetinib, an MEK inhibitor, to vemurafenib, a BRAF inhibitor, significantly improved progression-free survival [hazard ratio (HR), 0.58; P < 0.0001] and overall survival (HR, 0.70; P = 0.005) in advanced BRAF-mutated melanoma. Here, we report on the incidence, course, and management of key adverse events (AEs) in the coBRIM study. Patients and methods: Patients were randomly assigned 1:1 to receive vemurafenib (960 mg twice a day) and either cobimetinib (60 mg once a day, 21 days on/7 days off) or placebo. In addition to standard safety evaluations, patients underwent regular ophthalmic, cardiac, and dermatologic surveillance examinations. Results: Of 495 patients recruited to the study, 493 patients received treatment and constituted the safety population (cobimetinib combined with vemurafenib, 247; vemurafenib, 246). At data cut-off (30 September 2015), median follow-up was 18.5 months. Nearly every patient experienced an AE. In patients who received cobimetinib combined with vemurafenib, the frequency of grade ≥3 AEs was higher than in patients who received vemurafenib alone (75% versus 61%). Most AEs, including grade ≥3 AEs, occurred within the first treatment cycle. After the first cycle (28 days), the incidence of common AEs (rash, diarrhoea, photosensitivity, elevated creatine phosphokinase, serous retinopathy, pyrexia, and liver laboratory abnormalities) decreased substantially over time. Most AEs were managed conservatively by supportive care measures, dose modifications of study treatment, and, occasionally, permanent treatment discontinuation. Conclusions: These data indicate that most AEs arising from treatment with cobimetinib combined with vemurafenib generally occur early in the treatment course, are mild or moderate and are manageable by patient monitoring, dose modification and supportive care. ClinicalTrials.gov: NCT01689519. [ABSTRACT FROM AUTHOR]

Published
2017
Full Text
View/download PDF

6. Vemurafenib and cobimetinib combination therapy for BRAFV600E-mutated melanoma favors posterior reversible encephalopathy syndrome

Author

B. Henning, S. Bittner, F. Zipp, Carmen Loquai, F. Luessi, and S. Engel

Subjects
Oncology, Cobimetinib, medicine.medical_specialty, Combination therapy, business.industry, Melanoma, Posterior reversible encephalopathy syndrome, Hematology, medicine.disease, chemistry.chemical_compound, Text mining, chemistry, Internal medicine, medicine, Vemurafenib, business, medicine.drug
Published
2019

7. A phase Ib study of the safety and efficacy of atezolizumab (atezo) + bevacizumab (bev) + cobimetinib (cobi) in patients (pts) with metastatic colorectal cancer (mCRC)

Author

Xueping Qu, Neil H. Segal, Antonio Cubillo, M. Merchant, Johanna C. Bendell, H. Zeuner, Kanwal Pratap Singh Raghav, Guillem Argiles, Christopher H. Lieu, Yibing Yan, and J.D. Gallo

Subjects
Cobimetinib, Oncology, medicine.medical_specialty, Bevacizumab, business.industry, Cancer, Hematology, medicine.disease, Oxaliplatin, Irinotecan, chemistry.chemical_compound, chemistry, Response Evaluation Criteria in Solid Tumors, Atezolizumab, Internal medicine, medicine, Progression-free survival, business, medicine.drug
Published
2019

8. 1137P Incidence and time course of adverse events (AEs) with atezolizumab (A) in combination with vemurafenib (V) and cobimetinib (C) in the phase III IMspire150 study

Author

L. de la Cruz Merino, Judit Oláh, V. McNally, P.A. Ascierto, Haocheng Li, C. Robert, Karl D. Lewis, Q. Zhu, Jacek Mackiewicz, Grant A. McArthur, Rodrigo Ramella Munhoz, Edward McKenna, R. Gutzmer, Paola Queirolo, and G. Liszkay

Subjects
Oncology, Cobimetinib, medicine.medical_specialty, business.industry, Incidence (epidemiology), Hematology, chemistry.chemical_compound, chemistry, Atezolizumab, Internal medicine, Time course, medicine, Vemurafenib, Adverse effect, business, medicine.drug
Published
2020

9. SO-32 Biomarker analysis of the phase III IMblaze370 trial of atezolizumab plus cobimetinib or atezolizumab monotherapy vs regorafenib in third-line CRC

Author

L. Roberts, Johanna C. Bendell, Tark Kim, Sami Mahrus, Matthew Wongchenko, Guillem Argiles, Xueping Qu, A. Uyei, Kelly DuPree, Yibing Yan, Fortunato Ciardiello, and Yi Shi

Subjects
Oncology, Cobimetinib, medicine.medical_specialty, business.industry, Hematology, chemistry.chemical_compound, Third line, chemistry, Atezolizumab, Internal medicine, Regorafenib, medicine, Biomarker Analysis, business
Published
2020

10. Interim analysis of a phase Ib study of cobimetinib plus atezolizumab in patients with advanced BRAFV600 wild type melanoma progressing on prior anti-PD-L1 therapy

Author

Georgina V. Long, M Gonzalez Cao, Shahneen Sandhu, A. Soria Rivas, Ivor Caro, Victoria Atkinson, Y. Song, L. Roberts, Theresa Medina, and Yibing Yan

Subjects
0301 basic medicine, Cobimetinib, medicine.medical_specialty, business.industry, Disease progression, Anti pd 1, Hematology, Interim analysis, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, Oncology, chemistry, Atezolizumab, 030220 oncology & carcinogenesis, Family medicine, Partial response, medicine, In patient, business, Advanced melanoma
Abstract

Background Treatment options for patients (pts) with BRAFV600 wild type advanced melanoma following failure on anti–programmed death receptor 1 (aPD-1) therapy are limited. Melanoma is strongly driven by MAPK signaling. The MEK inhibitor cobimetinib inhibits MAPK signaling and increases immune cell infiltrate in the tumor, providing a strong rationale for combining cobimetinib with the anti–PD ligand-1 (PD-L1) antibody atezolizumab. Methods This multisite, phase Ib study enrolled pts with BRAFV600 wild type advanced melanoma with disease progression on or after aPD-1 therapy (≤12 weeks before study entry) to 2 cohorts. In cohort A, pts received oral cobimetinib 60 mg (once daily, 21 days on, 7 days off) and IV atezolizumab 840 mg (every 2 weeks). In cohort B, pts received identical treatment except in cycle 1, in which cobimetinib was dosed alone for the first 14 days. Paired pretreatment and during-treatment (cycle 2) tumor biopsies were mandated in cohort B. The co-primary endpoints were confirmed objective response rate per RECIST v1.1 and disease control rate (DCR; complete response, partial response [PR], or stable disease [SD] at 16 weeks). Safety was a secondary endpoint (CTCAE v4.0). Results At data cutoff (March 1, 2019), 103 pts were enrolled in cohorts A (n = 92) and B (n = 11); 50 pts had >16 weeks of follow-up and were included in this analysis. Of these 50 pts, 8 (16%) had PR as best confirmed response and 18 (36%) had SD; the DCR was 38% (PR = 8; SD at 16 weeks=11). Prior aPD-1 therapy in 9 pts with unconfirmed PR included pembrolizumab (n = 5), nivolumab (n = 1), pembrolizumab + ipilimumab (n = 2), or nivolumab + ipilimumab (n = 1). For the 7 pts with confirmed PR whose tumor PD-L1 status could be established, 6 were positive (≥1% PD-L1+ cells) and 1 was negative ( Conclusions Preliminary efficacy and safety data for the combination of cobimetinib and atezolizumab in pts who have disease progression on/after prior aPD-1 therapy suggest that this is a feasible and active option warranting further exploration. Clinical trial identification NCT03178851. Editorial acknowledgement ApotheCom, Yardley, PA, USA. Legal entity responsible for the study Roche. Funding Roche. Disclosure S.K. Sandhu: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Merck Serono; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy: Merck Sharp and Dohme; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche Genentech; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Research grant / Funding (institution): Endocyte. V.G. Atkinson: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Serono; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Travel / Accommodation / Expenses: Onco-Sec. M. Gonzalez Cao: Honoraria (self), Honoraria (institution), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (institution), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (institution): MSD; Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Travel / Accommodation / Expenses: Takeda. T. Medina: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Array; Research grant / Funding (institution): Dynavax; Research grant / Funding (institution): Immunocore; Research grant / Funding (institution): Nektar; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Checkmate. A. Soria Rivas: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Serono. I. Caro: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche Genentech. L. Roberts: Full / Part-time employment: Genentech. Y. Song: Full / Part-time employment: Roche/Genentech. Y. Yan: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche/Genentech. G.V. Long: Advisory / Consultancy: Aduro; Advisory / Consultancy: Amgen; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Mass-Array; Advisory / Consultancy: Merck Sharp and Dohme; Advisory / Consultancy: Novartis; Advisory / Consultancy: Oncosec; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Roche.

Published
2019

11. Combination treatment with cobimetinib (C) and atezolizumab (A) vs pembrolizumab (P) in previously untreated patients (pts) with BRAFV600 wild type (wt) advanced melanoma: Primary analysis from the phase III IMspire170 trial

Author

Piotr Rutkowski, J.M.G. Larkin, Lev V. Demidov, Yibing Yan, Athina Voulgari, Ana Arance, Keith T. Flaherty, Bethany Pitcher, Zeynep Eroglu, Helen Gogas, Jacek Mackiewicz, Jacopo Pigozzo, B. Dréno, Daniil Stroyakovskiy, Pier Francesco Ferrucci, S. Troutman, and Isabelle Rooney

Subjects
Cobimetinib, medicine.medical_specialty, business.industry, Immune checkpoint inhibitors, Melanoma, Wild type, Hematology, Pembrolizumab, medicine.disease, Gastroenterology, chemistry.chemical_compound, Combined treatment, Oncology, chemistry, Atezolizumab, Internal medicine, medicine, business, Advanced melanoma
Published
2019

12. Long-term efficacy of combination nivolumab and ipilimumab for first-line treatment of advanced melanoma: A network meta-analysis

Author

Kabirraaj Toor, K. Chan, P. Mohr, Andriy Moshyk, M. Besada, S. Goring, H.M. Johnson, and Srividya Kotapati

Subjects
Oncology, Cobimetinib, Trametinib, medicine.medical_specialty, business.industry, MEK inhibitor, Dabrafenib, Binimetinib, Hematology, Pembrolizumab, chemistry.chemical_compound, chemistry, Internal medicine, medicine, Nivolumab, Vemurafenib, business, medicine.drug
Abstract

Background Targeted and checkpoint inhibitor therapies for advanced melanoma have led to major improvements in overall survival (OS). Using long-term evidence, the objective was to estimate the relative efficacy of nivolumab plus ipilimumab (NIVO+IPI) vs. relevant comparators among treatment-naive patients with advanced, unresectable stage III/IV melanoma. Methods A systematic literature review of randomized controlled trials (RCTs) of first-line advanced melanoma therapies was conducted in November 2018. Key comparators were immunotherapies (NIVO+IPI; NIVO; pembrolizumab [PEM]), and BRAF+MEK inhibitors (dabrafenib + trametinib [DAB+TRAM]; encorafenib + binimetinib [ENC+BIN]; vemurafenib + cobimetinib [VEM+COB]). Bayesian network meta-analysis (NMA) models were used to estimate comparative OS. The NMAs used models of constant (overall) hazard ratio (HR) over time, and fractional polynomials to estimate time-varying HR, along with 95% credible intervals (CrI). Subgroup analyses and alternate models were explored to evaluate effect modification of immunotherapies by BRAF-mutation status. Results In total, 12 RCTs formed the network of evidence for OS (maximum follow-up: 30 to 60 months). For NIVO+IPI vs. each BRAF+MEK inhibitor, the HR decreased steadily over time. The hazard of death was similar by 6 months and lower at 12 months; thereafter, NIVO+IPI was associated with a significantly reduced hazard of death. At 18 months, HRs for NIVO+IPI vs. each BRAF+MEK inhibitor ranged from 0.45 to 0.52; by 42 months (longest duration of observed data for BRAF+MEK inhibitors), HRs were 0.24 to 0.29 (all CrIs Conclusions NIVO+IPI confers similar or sustained improvements in long-term OS compared with immunotherapies and BRAF+MEK inhibitors. Legal entity responsible for the study The authors. Funding Bristol-Myers Squibb. Disclosure P. Mohr: Honoraria (self), To manually add email to ESMO: To manually add email to ESMO. K. Toor: Full / Part-time employment, KT is an employee of Precision Xtract. Precision Xtract received funding for this project from Bristol-Myers Squibb: Precision Xtract. S. Goring: Advisory / Consultancy, SG acted as a consultant to Precision Xtract. Precision Xtract received funding for this project from Bristol-Myers Squibb: Precision Xtract. K. Chan: Full / Part-time employment, KC is an employee of Precision Xtract. Precision Xtract received funding for this project from Bristol-Myers Squibb: Precision Xtract. M. Besada: Full / Part-time employment, MB is an employee of Precision Xtract. Precision Xtract received funding for this project from Bristol-Myers Squibb: Precision Xtract. H.M. Johnson: Advisory / Consultancy: Bristol-Myers Squibb. A. Moshyk: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. S. Kotapati: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb.

Published
2019

13. Prognostic impact of early complete metabolic response on FDG-PET, in BRAF V600 mutant metastatic melanoma patients treated with combination vemurafenib & cobimetinib

Author

Nicholas Choong, Adil Daud, A. Ribas, Rodney J. Hicks, J. Frederickson, Thomas F. Gajewski, Anna C. Pavlick, Omid Hamid, D. Colburn, Grant A. McArthur, Jason Callahan, I. Puzanov, Matthew Wongchenko, W. Xu, and Ricardo J. Gonzalez

Subjects
Cobimetinib, Metastatic melanoma, business.industry, Complete Metabolic Response, Mutant, Hematology, chemistry.chemical_compound, Oncology, chemistry, Cancer research, Medicine, business, Vemurafenib, medicine.drug
Published
2017

14. Efficacy and safety results from IMblaze370, a randomised Phase III study comparing atezolizumab+cobimetinib and atezolizumab monotherapy vs regorafenib in chemotherapy-refractory metastatic colorectal cancer

Author

Mark Kozloff, Cathy Eng, Marwan Fakih, Johanna C. Bendell, A. Uyei, Tae Hwan Kim, Niall C. Tebbutt, Alberto Sobrero, Neil H. Segal, J. Tabernero, M. Di Bartolomeo, L. Roberts, Fortunato Ciardiello, Alfredo Falcone, Yibing Yan, Yi Shi, and Ilsung Chang

Subjects
0301 basic medicine, Oncology, Cobimetinib, medicine.medical_specialty, Chemotherapy, Randomization, Colorectal cancer, business.industry, medicine.medical_treatment, Hematology, medicine.disease, Chemotherapy regimen, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, chemistry, Refractory, Atezolizumab, 030220 oncology & carcinogenesis, Internal medicine, Regorafenib, medicine, business
Published
2018

15. Impact of duration of response (DOR) on overall survival (OS) in patients with metastatic melanoma treated with dacarbazine (DTIC), vemurafenib (V), or cobimetinib plus vemurafenib (C+V): a pooled analysis

Author

Yeung-Chul Mun, James Larkin, Brigitte Dréno, P.A. Ascierto, Karl D. Lewis, Edward McKenna, Keith T. Flaherty, Qian Zhu, Antoni Ribas, Grant A. McArthur, and Axel Hauschild

Subjects
Cobimetinib, Oncology, medicine.medical_specialty, Metastatic melanoma, business.industry, Hematology, chemistry.chemical_compound, Pooled analysis, chemistry, Internal medicine, Overall survival, Medicine, In patient, Dacarbazine - DTIC, business, Vemurafenib, medicine.drug
Published
2017

16. Prognostic subgroups and impact of treatment for post-progression overall survival (ppOS) in patients (pts) with BRAFV600-mutated metastatic melanoma treated with dacarbazine (DTIC) or vemurafenib (VEM) ± cobimetinib (COBI): A pooled analysis

Author

Q. Zhu, P.A. Ascierto, Yeung-Chul Mun, Grant A. McArthur, Edward McKenna, J.M.G. Larkin, Keith T. Flaherty, Karl D. Lewis, Brigitte Dréno, Axel Hauschild, and Antoni Ribas

Subjects
Oncology, Cobimetinib, medicine.medical_specialty, Metastatic melanoma, business.industry, Hematology, 01 natural sciences, 010101 applied mathematics, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pooled analysis, chemistry, 030220 oncology & carcinogenesis, Internal medicine, Overall survival, Medicine, In patient, 0101 mathematics, Dacarbazine - DTIC, business, Vemurafenib, medicine.drug
Published
2016

17. Cobimetinib plus vemurafenib to treat unresectable or metastatic melanoma: Data from the French temporary authorization for use

Author

Christine Mateus, M. Mouri, Ouidad Zehou, M. Moreau, C. Lebbé, Brigitte Dréno, A. Gorana, A. Bardet, Nicolas Meyer, and D-M. Anne-Bénédicte

Subjects
Cobimetinib, Oncology, medicine.medical_specialty, Metastatic melanoma, business.industry, Authorization, Hematology, chemistry.chemical_compound, chemistry, Internal medicine, medicine, Vemurafenib, business, medicine.drug
Published
2016

18. Preliminary safety and clinical activity of atezolizumab combined with cobimetinib and vemurafenib in BRAF V600-mutant metastatic melanoma

Author

Manish R. Patel, G. Mwawasi, Rene Gonzalez, Ryan J. Sullivan, Edward Cha, Marcus Ballinger, Karl D. Lewis, N. Richie, J. R. Infante, Jeffrey Wallin, F.S. Hodi, Omid Hamid, and Patrick Hwu

Subjects
0301 basic medicine, Cobimetinib, Metastatic melanoma, business.industry, Mutant, Hematology, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, Oncology, chemistry, Atezolizumab, 030220 oncology & carcinogenesis, Cancer research, medicine, Vemurafenib, business, medicine.drug
Published
2016

19. First-line cobimetinib (C) + paclitaxel (P) in patients (pts) with advanced triple-negative breast cancer (TNBC): Updated results and tumoral immune cell infiltration data from the phase 2 COLET study

Author

Matthew Wongchenko, Elizabeth Tan-Chiu, José A. García-Sáenz, Marleen Borms, Luc Dirix, S-B Kim, Adam Brufsky, J. Vanˇásek, B. Simmons, David Miles, Jung Ho Sohn, Yibing Yan, Joseph A. Sparano, M.M. Moezi, M-C. Liu, Mark Kozloff, V. McNally, Thierry Velu, J.I. Delgado Mingorance, and N. Xu

Subjects
Oncology, Cobimetinib, medicine.medical_specialty, business.industry, First line, Hematology, chemistry.chemical_compound, Paclitaxel, chemistry, Internal medicine, medicine, In patient, business, Immune cell infiltration, Triple-negative breast cancer
Published
2016

20. CONVERCE: evaluation of cobimetinib and vemurafenib combination treatment in patients with brain metastases from BRAFV600 mutated melanoma

Author

C. Lebbé, M.-T. Leccia, A. Mahmoudi, Thierry Lesimple, and Boris Campillo-Gimenez

Subjects
0301 basic medicine, Oncology, Cobimetinib, medicine.medical_specialty, business.industry, Melanoma, Hematology, medicine.disease, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, Combined treatment, chemistry, 030220 oncology & carcinogenesis, Internal medicine, medicine, In patient, Vemurafenib, business, medicine.drug
Published
2016

21. Genomic features of complete responders (CR) versus fast progressors (PD) in patients with BRAFV600-mutated metastatic melanoma treated with cobimetinib + vemurafenib or vemurafenib alone

Author

Claus Garbe, C. Robert, Jessie J. Hsu, Ivor Caro, P.A. Ascierto, Matthew Wongchenko, Paul B. Chapman, Antoni Ribas, J. A. Sosman, Grant A. McArthur, James Larkin, Brigitte Dréno, Ilsung Chang, Isabelle Rooney, Michele Maio, and Yibing Yan

Subjects
0301 basic medicine, Oncology, Cobimetinib, medicine.medical_specialty, Metastatic melanoma, business.industry, Hematology, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, chemistry, 030220 oncology & carcinogenesis, Internal medicine, medicine, In patient, business, Vemurafenib, medicine.drug
Published
2016

22. LBA-01 Safety and efficacy of cobimetinib (cobi) and atezolizumab (atezo) in a Phase 1b study of metastatic colorectal cancer (mCRC)

Author

J. R. Infante, Jeffrey Wallin, C. Cheng Ean, Bang Yung-Jue, Johanna C. Bendell, J. Lewin, Jayesh Desai, M. Das Thakur, G. Mwawasi, K. Tae Won, Edward Cha, and Carrie B. Lee

Subjects
0301 basic medicine, Cobimetinib, Oncology, medicine.medical_specialty, business.industry, Colorectal cancer, Hematology, medicine.disease, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, chemistry, Atezolizumab, 030220 oncology & carcinogenesis, Internal medicine, medicine, business
Published
2016

23. Vemurafenib and Cobimetinib Potently Inhibit Ps6 Signaling in Brafv600 Mutation–Positive Locally Advanced or Metastatic Melanoma from Brim7 Study

Author

Yulei Wang, Grant A. McArthur, Matthew Wongchenko, Antoni Ribas, Shan Lu, Nicholas Choong, Thomas F. Gajewski, Yibing Yan, Igor Puzanov, Omid Hamid, and Rene Gonzalez

Subjects
MAPK/ERK pathway, Oncology, Cobimetinib, medicine.medical_specialty, Mutation, medicine.diagnostic_test, business.industry, MEK inhibitor, Mitogen-Activated Protein Kinase Inhibitor, Hematology, medicine.disease_cause, chemistry.chemical_compound, chemistry, Internal medicine, Biopsy, medicine, Cancer research, Immunohistochemistry, Vemurafenib, business, medicine.drug
Abstract

Aim: Combined BRAF and MEK inhibition, compared with BRAF inhibitor alone, may delay the onset of resistance. Vemurafenib + cobimetinib (vem + cobi) was evaluated in patients naive to or previously treated with BRAF inhibitor (BRAFi) in a phase Ib trial: BRIM7 (NCT01271803). Modulation of signaling pathways and transcriptional profiles were assessed in tumor samples. Methods: Tumor tissues were collected at baseline, on-treatment at cycle 1 day 14 (C1D14), and at disease progression (PD). Modulation of cell-signaling pathways was assessed in tumor biopsy specimens by immunohistochemistry (IHC) or reverse-phase protein array (RPPA). Tumor transcriptional profiles were measured on a NanoString platform. Results: pERK levels were inhibited an average of 86 ± 14% with vem + cobi in paired biopsy specimens (n = 7) at C1D14 compared with baseline, which coincided with enhanced down-regulation of ERK transcriptional targets, compared with vem alone (n = 20). Cytoplasmic pERK was inhibited by 92 ± 3% in BRAFi-naive patients and by 95 ± 3% in patients with PR/CR responses. The inhibition of S6 ribosomal protein phosphorylation (pS6) showed significant differences based on treatment response and prior treatment status. By IHC, pS6 levels were clearly reduced in BRAFi-naive patients (82 ± 8%) compared with patients whose disease progressed with BRAFi treatment (31 ± 22%) and similarly in PR/CR patients (88 ± 11%) vs PD/SD patients (33 ± 19%). These observations were verified in independent samples by RPPA: levels of pS6 (S235/236 and S240/244) and a pS6 downstream effector, p4EBP1 (T37/46), were significantly inhibited in the same patients. At PD, tumor pERK, pS6, and Ki67 inhibition were attenuated to different degrees in each patient, whereas transcriptional programs largely reverted to baseline profiles. Conclusions: Vem + cobi treatment resulted in robust modulation of tumor cell signaling and transcriptional programs. In concordance with reports for single-agent BRAF or MEK inhibitor treatment, potent inhibition of pS6 was observed in BRAFi-naive patients and patients with PR/CR, which may contribute to the enhanced response to the vem + cobi combination. Disclosure: Y. Yan: Employee of Genentech, Inc.; G. McArthur: Consultant: Roche-Genentech, Novartis, GSK, BMS, Millenium, Amgen Research: Pfizer, Millenium, Novartis; T. Gajewski: Consultant: Bayer, B-I, Abbvie, Roche/Genentech, Jounce, Dendreon, Amgen Investigator: BMS, Merck, Roche/Genentech, Incyte, Ono; I. Puzanov: Consultant: Roche (honoraria) Investigator: Roche/Genentech (funds to university); O. Hamid: Research/advisory board/consultant/speaker: Genentech; R. Gonzalez: Research/consultant/honoraria: GSK, Roche/Genentech, BMS; Y. Wang: Employee: Genentech; S. Lu: Employee: Genentech; M. Wongchenko: Employee: Genentech; N.W. Choong: Employee: Roche/Genentech Stockholder: Roche; A. Ribas: Consultant: Amgen, GSK, Genentech, Merck Stockholder: Kite Pharma.

Published
2014

24. Phase 3, Double-Blind, Placebo-Controlled Study of Vemurafenib Versus Vemurafenib + Cobimetinib in Previously Untreated Brafv600 Mutation–Positive Patients with Unresectable Locally Advanced or Metastatic Melanoma (Nct01689519)

Author

Claus Garbe, Victoria Atkinson, Mario Mandalà, Antoni Ribas, L. De La Cruz Merino, Caroline Dutriaux, Stephen P. Hack, James Larkin, Daniil L. Stroyakovsky, Grant A. McArthur, Luc Thomas, Lev V. Demidov, Gabriella Liszkay, I. Chang, Brigitte Dréno, Paolo A. Ascierto, and Michele Maio

Subjects
Cobimetinib, medicine.medical_specialty, education.field_of_study, biology, business.industry, Incidence (epidemiology), Population, Placebo-controlled study, Hematology, Gastroenterology, Discontinuation, chemistry.chemical_compound, Oncology, chemistry, Internal medicine, medicine, biology.protein, Creatine kinase, Adverse effect, Vemurafenib, business, education, medicine.drug
Abstract

was 68% in the combination and 45% in the control arm (P

Published
2014

Catalog

Books, media, physical & digital resources
See catalog results