1049OSAFETY AND EFFICACY OF MPDL3280A (ANTI-PDL1) IN COMBINATION WITH BEVACIZUMAB (BEV) AND/OR CHEMOTHERAPY (CHEMO) IN PATIENTS (PTS) WITH LOCALLY ADVANCED OR METASTATIC SOLID TUMORS

• Published in: Annals of oncology Vol. 25; no. suppl_4; p. iv361
• Main Authors: Lieu, C., Bendell, J., Powderly, J.D., Pishvaian, M.J., Hochster, H., Eckhardt, S.G., Funke, R., Rossi, C., Waterkamp, D., Hurwitz, H.
• Format: Journal Article
• Language: English
• Published: Oxford University Press 01-09-2014
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdu342.2

Abstract
Aim: PD-L1 mediates cancer immune evasion, and blocking PD-L1 represents a cancer immunotherapy strategy that can restore tumor-specific T-cell immunity. MPDL3280A, a human monoclonal antibody containing an engineered Fc-domain, targets PD-L1, preventing binding to its receptors PD-1 and B7.1 on activated T cells. MPDL3280A does not disrupt the PD-L2/PD-1 interaction, which may mitigate autoimmune lung toxicity. As VEGF blockade is proposed to synergize with immunotherapy, and certain chemos may augment immune responses, we examined MPDL3280A with bev and/or chemo.
Methods: This open-label, multicenter phase Ib study evaluated the safety and preliminary efficacy of MPDL3280A with bev (Arm A, refractory tumors or 1L renal cell carcinoma [RCC]) and bev + FOLFOX (Arm B, oxaliplatin-naive tumors) in pts with locally advanced or metastatic solid malignancies. Pts received MPDL3280A 20 mg/kg q3w (Arm A) or 15 mg/kg q2w (Arm B), and bev 15 mg/kg q3w (Arm A) or 10 mg/kg q2w (Arm B). Chemo was given at standard doses. Objective responses were assessed by RECIST 1.1.
Results: As of Jan 21, 2014, 33 pts in Arm A and 29 pts in Arm B were treated; Arm A 1L RCC patients had short follow-up. Most pts had CRC (39% and 79% in Arms A and B, respectively). Grade 3/4 AEs regardless of attribution occurred in 42% of Arm A pts, including abdominal pain, hyperbilirubinemia, pneumonia and tumor pain (6% each), and in 52% of Arm B pts, including neutropenia (31%) and diarrhea (14%). No MPDL3280A-related infusion reactions occurred. SAEs occurred in 30% and 17% of pts in Arms A and B, respectively. RECIST responses were observed in 3 Arm A pts (CRC, melanoma, breast cancer) and 11 Arm B pts (10 CRC, 1 breast cancer). One Arm B pt (RCC) had a CR. Updated results will be presented.
Conclusions: MPDL3280A + bev ± chemo was well tolerated and no unexpected toxicity was observed. Responses were observed in a variety of tumors. Further evaluation of MPDL3280A combination regimens in pts with advanced or metastatic solid tumors is warranted.
Disclosure: C. Lieu: Sanofi Aventis consultant; J.D. Powderly: : Leadership position: Biologics Human Application Lab. Advisor: Genentech, BMS, Amplimmune, and Merck. BMS. Research funding: Genentech, BMS, Amplimmune, Merck, AstraZeneca, ImClone, and Eli Lilly. Speaker and advisor: BMS; H. Hochster: Genentech consultant; R. Funke, C. Rossi and D. Waterkamp: is an employee of Genentech, Inc.;H. Hurwitz: Research funding from Genentech, Roche, Bristol-Myers Squibb, Pfizer, Sanofi, Regeneron, GlaxoSmithKline, and Amgen. Advisor to Genentech, Roche, Bristol-Myers Squibb, Pfizer, Sanofi, Regeneron, GlaxoSmithKline, and Amgen. All other authors have declared no conflicts of interest.