Abstract CT055: Phase 1/2 primary analysis of ZUMA-6: Axicabtagene ciloleucel (Axi-Cel) in combination With atezolizumab (Atezo) for the treatment of patients (Pts) with refractory diffuse large B cell lymphoma (DLBCL)
Authors: Jacobson Caron A. , Westin Jason R. , Miklos David B. , Herrera Alex F. , Lee Jennifer , Seng Judy , Rossi John M. , Sun Jennifer , Dong Jinghui , Roberts Zachary J. , Vezan Remus , Avanzi Mauro P. , Locke Frederick L. 
Published: September 2020

Abstract
Background: Axi-cel is a US and EU-approved autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy for the treatment of adult relapsed/refractory LBCL after ≥ 2 prior lines of therapy. In ZUMA-1, the objective response rate (ORR) was 83% (58% complete response [CR] rate; Locke et al. Lancet Oncol. 2019). As checkpoint proteins (eg, PD-1, PD-L1) have been shown to be upregulated after CAR T cell infusion (Perez et al. ASH 2015. #2042; Galon et al. ASCO 2017. #3025; Neelapu et al. ASH 2017. #578; Arihara et al. SITC 2019. #P210), ZUMA-6 examined outcomes of axi-cel combined with the anti-PD-L1 antibody atezo (NCT02926833). Methods: Adult pts (≥18 y) with refractory DLBCL who received prior CD20-targeting and anthracycline-containing regimen, had ECOG ≤ 1, and had adequate bone marrow and organ function were eligible. Pts received conditioning (fludarabine 30 mg/m2/d + cyclophosphamide 500 mg/m2/d for 3 days) followed by a targeted 2 × 106 CAR T cells/kg. In Phase 1, atezo was given at 1200 mg every 21 days for 4 doses starting on Day 21, 14, and 1 post-axi-cel infusion for Cohorts 1, 2, and 3, respectively. Given Phase 1 results, pts received the Cohort 3 atezo (Day +1) dosing schedule in Phase 2. The primary endpoint was incidence of dose-limiting toxicities for Phase 1 and CR rate for Phase 2. Secondary endpoints included adverse events (AEs), response, and CAR T cell levels. Pooled data are reported for Phase 1 Cohort 3 and Phase 2 pts. Results: As of 2/21/19, 28 pts received axi-cel and ≥ 1 atezo dose; 18/28 pts received all 4 atezo doses. Median age was 58 y (range, 42 - 71). Most pts (86%) had received ≥ 2 prior therapies (4 had primary refractory disease), and 46% had an IPI score of 3 or 4. All pts experienced ≥ 1 AE (86% Grade [Gr] ≥ 3). There was 1 Gr 5 AE of multiple organ dysfunction syndrome unrelated to axi-cel or atezo. Gr ≥ 3 CRS occurred in 4% of pts, and Gr ≥ 3 neurologic events (NEs) occurred in 29%. With a median follow-up of 10.2 mo, the best ORR was 75% (46% CR rate); 46% of pts were in ongoing response. Median DOR, PFS, and OS were not reached; KM estimated 6-mo rates were 62%, 50%, and 71%, respectively. Median peak CAR T cell levels were similar in ZUMA-6 and ZUMA-1 (ZUMA-6: 37 cells/µL [range, 0.07 - 196]; ZUMA-1: 32 cells/µL [range, 1 - 1513]). Median CAR T cell expansion as measured by area under the curve in the first 28 days was also similar (ZUMA-6: 497 cells/µL × days [range, 0.002 - 2222]; ZUMA-1: 357 cells/µL × days [range, 5 - 11,507]). Levels of key cytokines, including those related to CRS and/or NEs, will be presented. Conclusions: PD-L1 blockade with atezo after axi-cel has a manageable safety profile, consistent with that observed in ZUMA-1, with no significant evidence of increased incidence of AEs. Efficacy outcomes and CAR T cell level results of axi-cel combined with atezo were similar to those of pts treated with axi-cel alone.
Citation Format: Caron A. Jacobson, Jason R. Westin, David B. Miklos, Alex F. Herrera, Jennifer Lee, Judy Seng, John M. Rossi, Jennifer Sun, Jinghui Dong, Zachary J. Roberts, Remus Vezan, Mauro P. Avanzi, Frederick L. Locke. Phase 1/2 primary analysis of ZUMA-6: Axicabtagene ciloleucel (Axi-Cel) in combination With atezolizumab (Atezo) for the treatment of patients (Pts) with refractory diffuse large B cell lymphoma (DLBCL) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT055.