1109PD - Preliminary safety and clinical activity of atezolizumab combined with cobimetinib and vemurafenib in BRAF V600-mutant metastatic melanoma

Date 10 October 2016
Event ESMO 2016 Congress
Session Melanoma and other skin tumours
Topics Skin cancers
Melanoma
Presenter Patrick Hwu
Citation Annals of Oncology (2016) 27 (6): 379-400. 10.1093/annonc/mdw379
Authors 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
  • 1Melanoma Medical Oncology, MD Anderson Cancer Center, 77030 - Houston/US
  • 2Melanoma Therapeutics, The Angeles Clinic and Research Institute, CA 90025 - Los Angeles/US
  • 3Oncology, University of Colorado Comprehensive Cancer Center, Aurora/US
  • 4Drug Development Program, Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville/US
  • 5Sarah Cannon Research Institute, Florida Cancer Specialists, 34232 - Sarasota/US
  • 6Oncology, Dana-Farber Cancer Institute, Boston/US
  • 7Oncology, Genentech, Inc., 94080 - South San Francisco/US

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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

NCT01656642

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd

Funding

F. Hoffmann-La Roche Ltd

Disclosure

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.