Efficacy and safety of atezolizumab (atezo) and bevacizumab (bev) in a phase Ib study of microsatellite instability (MSI)-high metastatic colorectal cancer (mCRC).

• DOI: 10.1200/jco.2017.35.4_suppl.673
• Publication Date: 2017-03-21T17:08:11Z
• Authors: Howard S. Hochster; Johanna C. Bendell; James M. Cleary; Paul Foster; Wei Zhang; Xian He; Genevive Hernandez; Koho Iizuka; S. Gail Eckhardt
• Keywords: Atezolizumab; Tolerability; Microsatellite Instability

673 Background: Blockade of the PD-L1/PD-1 axis is a proven immunologic approach for treatment many cancers; however, not all pts respond to monotherapy. Bev, an anti–VEGF-A antibody, has demonstrated clinical efficacy in mCRC and enhanced T-cell infiltration tumors preclinical studies. Thus, we postulated that combining atezo (anti-PD-L1) with bev would augment anti-tumor immune responses, resulting improved more durable benefit. We report results from first study anti-PD-L1 agent + VEGF-A blockade MSI-high mCRC. Methods: A Ph Ib (NCT01633970) investigated various chemotherapeutic/biologic regimens (eg, bev) advanced solid tumors, including Pts received 1200 mg q3w plus 15 mg/kg (data cutoff, May 20, 2016). The primary objective was evaluate safety bev. Secondary objectives included activity per RECIST v1.1. MSI status tested locally. Results: Ten were enrolled. Three had 1 prior chemotherapy 7 ≥ 2. Median age 52.5 y. minimum (range) follow-up 2.6 (2.6-20.3) mo. duration 10.1 (2-20) 9.0 (2-19) mo, respectively. Efficacy are shown below; confirmed ORR v1.1 30% (95% CI, 6.7%-65.3%). OS been reached median 11.1 Treatment-related all-grade AEs occurred 80% pts; 40% related G3/4 AE. most common AE proteinuria (40%; n = 3 G2 G3). No G5 events occurred. One led discontinuation Biomarker data will be presented. Conclusions: Initial observed heavily pretreated receiving bev; disease control rate 90%. This combination well tolerated without unexpected toxicities. Further ongoing. Clinical trial information: NCT01633970. [Table: see text]