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Melanoma and other skin tumours

3426 - Preliminary safety and clinical activity of atezolizumab combined with cobimetinib and vemurafenib in BRAF V600-mutant metastatic melanoma


10 Oct 2016


Melanoma and other skin tumours


Patrick Hwu


Annals of Oncology (2016) 27 (6): 379-400. 10.1093/annonc/mdw379


P. Hwu1, O. Hamid2, R. Gonzalez3, J.R. Infante4, M.R. Patel5, F..S. Hodi6, K.D. Lewis3, J. Wallin7, G. Mwawasi7, E. Cha7, N. Richie7, M. Ballinger7, R. Sullivan6

Author affiliations

  • 1 Melanoma Medical Oncology, MD Anderson Cancer Center, 77030 - Houston/US
  • 2 Melanoma Therapeutics, The Angeles Clinic and Research Institute, CA 90025 - Los Angeles/US
  • 3 Oncology, University of Colorado Comprehensive Cancer Center, Aurora/US
  • 4 Drug Development Program, Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville/US
  • 5 Sarah Cannon Research Institute, Florida Cancer Specialists, 34232 - Sarasota/US
  • 6 Oncology, Dana-Farber Cancer Institute, Boston/US
  • 7 Oncology, Genentech, Inc., 94080 - South San Francisco/US


Abstract 3426


Targeted therapy with MEK inhibitor cobimetinib (C) + BRAF inhibitor vemurafenib (V) in BRAFV600-mutant melanoma can result in anti-cancer immune activation and rapid clinical response. Inhibition of PD-L1 with atezolizumab (A; anti-PDL1) can also lead to anti-cancer immune activity and durable responses. Combining C + V with A, which may enhance and perpetuate antitumor immune activity, can potentially improve both clinical response and durability.


In a Phase 1b study, patients (pts) with untreated BRAFV600-mutant unresectable or metastatic melanoma received A + C + V after a 28 d run-in period with C + V. A was dosed IV q2w at 800 mg, C was PO QD at 60 mg for first 21 d of each 28 d cycle and V was PO BID at 960 mg during 1-21 d of run-in and 720 mg subsequently.


14 pts who received ≥ 1 dose of A were safety and efficacy evaluable. Median safety follow-up was 5.6 mo (range 1.5-12.8). All-grade (G) AEs that occurred in > 20% pts and reported as related to A and/or C and/or V were nausea, fatigue, flu-like symptoms, photosensitivity, maculopapular rash, elevated ALT/AST and bilirubin, mucosal inflammation and arthralgia. 6 pts had C- and/or V-related G3-4 AEs during run-in period, and 5 pts had A- and/or C- and/or V-related G3-4 AEs during the triple combination period; all were manageable and reversible. There were no unexpected AEs or G5 AEs. No A-related SAEs occurred. 1 pt discontinued all study treatment due to elevated ALT/AST. 13/14 pts (93%) showed responses (RECIST v1.1), including 1 CR and 12 PRs. 1 pt with PR had a 100% reduction in target lesions. Responses were unconfirmed, and median DOR and PFS were not estimable due to limited follow-up at the time of data cut (Feb 15, 2016). 11/13 pts continue in response. Updated data with functional biomarkers of T-cell activation will be presented.


A + C + V combination therapy results in a manageable safety profile and promising anti-tumor activity in pts with BRAFV600-mutant metastatic melanoma. These preliminary data show that anti-PDL1 therapy can be successfully combined with MEK and BRAF inhibitors and warrant further exploration. NCT01656642

Clinical trial identification


Legal entity responsible for the study

F. Hoffmann-La Roche Ltd


F. Hoffmann-La Roche Ltd


O. Hamid: Consultant, speaker and receives funding from: AstraZeneca Bristol-Myers Squibb. Celldex Genentech/Roche Immunocore Incyte Merck Merck Serono MedImmune Novartis Pfizer Rinat. R. Gonzalez: Grants recieved from Roche/Genentech, BMS, Merck, Amgen. Consultant fees from Roche/Genentech and Novartis. J.R. Infante: I have no personal financial conflicts of interest but my institution receives research funding and consulting from Genentech. F.S. Hodi: Non-paid advisor to Genentech, BMS, Merck; member of the Amgen advisory board; compenstated advisor to Novartis; received clinical trials support from Genentech, BMS, Merck and Novartis. J. Wallin, G. Mwawasi, E. Cha, N. Richie, M. Ballinger: Employee of Genentech, Inc. R. Sullivan: Grants from Merck, personal fees from Novartis, outside the submitted work. All other authors have declared no conflicts of interest.

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