A PHASE IB STUDY EVALUATING THE SAFETY AND CLINICAL ACTIVITY OF ATEZOLIZUMAB COMBINED WITH OBINUTUZUMAB IN PATIENTS WITH RELAPSED OR REFRACTORY NON‐HODGKIN LYMPHOMA (NHL)

Introduction: Outcomes for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) pts remain poor with modern chemo-immunotherapies. DLBCL and FL may escape immune surveillance partly due to increased PD-L1/PD-1 expression. Atezolizumab (atezo; anti–PD-L1) has shown activity in many cancers, including NHL. Obinutuzumab (obi; anti-CD20) also has activity in NHL. Here we report data from a Ph Ib study to determine if atezo + obi can reinvigorate immunity to enhance antitumor responses in R/R NHL (NCT02220842). Methods: All pts had measurable disease and ≥1 prior chemo-immunotherapy regimen. Primary endpoints were safety and tolerability; secondary endpoints were PK and clinical activity. Pts received obi IV on days 1 (100 mg), 2 (900 mg), 8 and 15 (1000 mg) of Cycle 1. In Cycles 2-8, atezo 1200 mg IV + obi 1000 mg IV were given on day 1 q3w. Maintenance with atezo followed for 6 mo. Response was reported by PET-CT or CT scan using the Lugano 2014 criteria. Biopsies (FL) were collected to assess PD-L1 (SP142 assay), CD8 and MHCI expression using IHC. Results: As of Nov 21, 2016, 49 pts (23 DLBCL; 26 FL) were safety evaluable (baseline characteristics in table). Pts were heavily pre-treated, with 87% of DLBCL pts refractory to last therapy. 30 pts had ≥1 any-grade TEAE. The most common Gr 3-4 TEAEs were pain (8.2%), anemia and neutropenia (6.1% each). AEs led to study drug interruptions in 13 pts.1 pt had atezo-related AEs leading to treatment discontinuation (Gr 2 diabetes mellitus and pain). Of 17 reported deaths, 15 were due to progression and 2 to unknown causes. At the end of induction assessment (after Cycle 10), 42 pts were efficacy evaluable (treatment characteristics in table). ORR (CR + PR) was 57% for FL and 16% for DLBCL. Most pts with CR/PR had CD8+ T-cell levels above the median. All FL pts with increased tumor-infiltrating CD8+ T cells after atezo + obi had a response; obi alone increased CD8+ T-cell infiltration in 5 of 6 pts. Loss of MHCI was detected in 2 of 35 evaluable pts (both DLBCL); median MHCI expression was similar in FL and DLBCL. PD-L1 and MHCI expression did not correlate with response. Conclusions: Atezo + obi was well tolerated and exhibited activity in R/R NHL. Biomarker analyses point to a more immune-rich environment in FL and suggest that established mechanisms of immune surveillance for DLBCL alone do not account for differences in activity. Changes in biomarker levels upon treatment demonstrate the dynamic nature of immune functionality biomarkers. Keywords: monoclonal antibodies (MoAb); non-Hodgkin lymphoma (NHL); obinutuzumab.