470P - Efficacy and safety of cobimetinib (cobi) and atezolizumab (atezo) in an expanded phase 1b study of microsatellite-stable (MSS) metastatic colorect...

Date 08 October 2016
Event ESMO 2016 Congress
Session Poster Display
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Cancer Immunology and Immunotherapy
Rectal Cancer
Presenter Jayesh Desai
Citation Annals of Oncology (2016) 27 (6): 149-206. 10.1093/annonc/mdw370
Authors J. Desai1, Y.S. Hong2, J.E. Kim2, T.W. Kim2, S.W. Han3, Y. Bang3, C.E. Chee4, V.Y.M. Heong4, A. McRee5, L.Q. Chow6, E.L. Kwak7, J.R. Infante8, J. Wallin9, M. Das Thakur9, G. Mwawasi9, P. Foster9, E. Cha9, J.C. Bendell8
  • 1Medical Oncology, Royal Melbourne Hospital, 3050 - Melbourne/AU
  • 2Department Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 138-736 - Seoul/KR
  • 3Oncology, Seoul National University Hospital, Seoul/KR
  • 4Oncology, The Cancer Institute National University Hospital, 119074 - Singapore/SG
  • 5Gi Medical Oncology, University of North Carolina - Chapel Hill, 27599-7305 - Chapel Hill/US
  • 6Department Of Medicine, Division Of Medical Oncology, University of Washington, Seattle/US
  • 7Oncology, Massachusetts General Hospital, Boston/US
  • 8Drug Development Program, Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville/US
  • 9Oncology, Genentech, Inc., 94080 - South San Francisco/US

Abstract

Background

MSS colorectal cancers, which comprise the vast majority of mCRC patients (pts), appear essentially resistant to PD-L1/PD-1 blockade vs many other tumors. Since inhibition of MEK promotes T cell accumulation intratumorally and combines with anti-PDL1 pre-clinically (Ebert, Immunity 2016), the combination of cobi (MEK inhibitor) and atezo (anti-PDL1) was evaluated in pts with mCRC.

Methods

44 mCRC pts were enrolled with 23 evaluable pts for efficacy, including 22 KRASmt and 1 KRASwt, who failed prior lines of therapy and were not selected by PD-L1 expression. Of these 23 pts, 3 were treated with cobi during escalation (2 at 20 mg; 1 at 60 mg) and 20 were treated during expansion (60 mg). Cobi was dosed PO for 21 d on/7 d off and atezo at 800 mg IV q2w. Primary endpoints were safety and tolerability. Secondary endpoints included investigator-assessed efficacy by RECIST v1.1. MSS status was confirmed centrally by mutation load profiling.

Results

As of Feb 12, 2016, the 23 efficacy evaluable mCRC pts had a median safety follow-up of 3.78 mo (range, 1.1-15.1). None were identified as MSI-H and the majority expressed low levels of PD-L1 at baseline. The 6 mo survival rate was 72% (95% CI: 52, 93). Confirmed responses were seen in 4 pts (17%) with duration ranging from 5.4 to 11.1 mo and were ongoing in 2 pts. Activity did not correlate with PD-L1 expression. All grade treatment-related AEs occurring in > 20% pts included diarrhea, fatigue, dermatitis acneiform, rash, maculopapular rash, pruritus, nausea, creatine phosphokinase increase and AST elevation, consistent with that seen for the single agents. G3-4 AEs related to either drug were seen in 8 pts (34.8%). The most common individual, related G3-4 AEs (diarrhea and rash) occurred in ≤ 2 pts (8.7%). No G5 AEs occurred. Four AEs led to discontinuation of cobi. No AEs led to atezo withdrawal. Updated biomarker data including anti-tumor immune markers will be presented.

Conclusions

In chemotherapy-refractory MSS mCRC where single-agent cobi and atezo have shown minimal activity, encouraging early results with the combination are observed for ORR, DOR, and 6 mo survival. Further trial follow-up is ongoing. NCT01988896

Clinical trial identification

NCT01988896

Legal entity responsible for the study

F. Hoffmann La-Roche Ltd.

Funding

F. Hoffmann La-Roche Ltd.

Disclosure

J.R. Infante: I have no personal financial conflicts of interest but my institution receives research funding and consulting from Genentech. J. Wallin, M. Das Thakur, G. Mwawasi, P. Foster, E. Cha: Genentech employee. All other authors have declared no conflicts of interest.