Background: Cancers can mediate immune evasion via upregulation of PD-L1; blocking PD-L1 may restore tumor-specific T-cell immunity. MPDL3280A, a human anti-PD-L1 mAb containing an engineered Fc domain, prevents PD-L1 binding to its receptors PD-1 and B7.1 on activated T cells. Single-agent MPDL3280A has shown clinical activity in various indications, including NSCLC, bladder cancer, RCC and CRC. VEGF blockade has shown immunomodulatory properties, and certain chemotherapies may have immunogenic effects. Therefore we examined the safety and efficacy of MPDL3280A + bev with or without FOLFOX. Methods: MPDL3280A + bev in refractory mCRC pts (Arm A) and MPDL3280A + bev + FOLFOX in oxaliplatin-naive mCRC pts (Arm B) were evaluated in an open-label, multicenter Phase Ib study. Arm A pts received MPDL3280A 20 mg/kg q3w and bev 15 mg/kg q3w. Arm B pts received MPDL3280A 14 mg/kg q2w, bev 10 mg/kg q2w and mFOLFOX6 at standard doses. Responses were assessed by RECIST v1.1. Potential biomarkers were assessed in pre- and on-treatment liver biopsies. The clinical data cutoff was July 7, 2014. Results: 14 mCRC pts in Arm A and 30 in Arm B were evaluable for safety. In Arm A, median age was 56 y, 29% were male and all had ≥3 prior systemic regimens. In Arm B, median age was 57 y, 53% were male and 70% had no prior systemic therapy. In Arm A, grade 3-4 AEs regardless of attribution were 64%, including abdominal pain, hyperbilirubinemia and pneumonia (14% each). 73% of Arm B pts had grade 3-4 AEs, including neutropenia (40%), diarrhea (13%), increased ALT (10%) and increased AST (10%). Grade ≥3 MPDL3280A-related AEs were 7% in Arm A and 20% in Arm B. For pts with ≥1 tumor assessment, the unconfirmed ORR was 8% (1/13) in Arm A and 36% (9/25) in Arm B. The unconfirmed ORR was 44% (8/18) for Arm B first-line pts. Minimum follow-up was 1.9 mo in Arm A and 2.2 mo in Arm B. Updated data, including biomarkers, will be presented. Conclusions: MPDL3280A + bev with or without FOLFOXwas well tolerated with no unexpected toxicities. Clinical activity was observed with both treatment combinations. Longer follow-up and randomized studies will be needed to estimate the potential benefit of adding MPDL3280A to chemotherapy. Clinical trial information: NCT01633970