1049O - Safety and efficacy of MPDL3280A (anti-PDL1) in combination with bevacizumab (bev) and/or chemotherapy (chemo) in patients (pts) with locally advan...

Date 27 September 2014
Event ESMO 2014
Session Immunotherapy of cancer
Topics Cancer Immunology and Immunotherapy
Presenter Christopher Lieu
Citation Annals of Oncology (2014) 25 (suppl_4): iv361-iv372. 10.1093/annonc/mdu342
Authors C. Lieu1, J. Bendell2, J.D. Powderly3, M.J. Pishvaian4, H. Hochster5, S.G. Eckhardt1, R. Funke6, C. Rossi7, D. Waterkamp8, H. Hurwitz9
  • 1Division Of Medical Oncology, University of Colorado Cancer Center, 80045 - Aurora/US
  • 2Drug Development Unit, Sarah Cannon Research Institute / Tennessee Oncology, 37203 - Nashville/US
  • 3Oncology, Carolina Bio-Oncology Institute, Huntersville/US
  • 4Hematology/oncology, Georgetown University, Washington, DC/US
  • 5None, Yale Cancer Center, New Haven/US
  • 6Biooncology, Genentech, Inc., South San Francisco/US
  • 7Biostatistics, Genentech, Inc., South San Francisco/US
  • 8Medical Director, Genentech, Inc., South San Francisco/US
  • 9Oncology, Duke University Medical Center, 27710 - Durham/US

 

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.