Polatuzumab Vedotin Plus Bendamustine and Rituximab in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Updated Results of a Phase Ib/II Randomized Study and Preliminary Results of a Single-Arm Extension

Introduction: Polatuzumab vedotin (Pola) is a novel antibody-drug conjugate targeting CD79b on B-cell non-Hodgkin lymphoma. In the randomized cohort of GO29365, a Phase [Ph] Ib/II study (NCT02257567; data cut-off: April 30, 2018), Pola plus bendamustine and rituximab (Pola+BR) improved progression-free survival (PFS) and overall survival (OS) compared with BR alone in patients (pts) with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). The study met its primary endpoint, with an independent review committee (IRC)-assessed complete response (CR) rate of 40.0% with Pola+BR vs 17.5% with BR. These results led to regulatory approvals of Pola+BR for the treatment of pts with R/R DLBCL. The study was later amended to include a single-arm Ph II extension (Ext) cohort of additional pts who received Pola+BR. Here, we report updated results from the GO29365 study, including the Ph Ib safety run-in cohort, Ph II randomized arms, and previously unpublished results from the Ext cohort. Methods: This open-label study enrolled pts with R/R DLBCL (aged ≥18 years, stem cell transplant [SCT]-ineligible, ECOG performance status of 0-2). Pts with Grade [Gr] >1 peripheral neuropathy [PN] were excluded. In the initial study, Pola+BR was investigated in DLBCL in a Ph Ib safety run-in cohort (Pola+BR; N=6) and Ph II randomized arms (Pola+BR vs BR; N=80); full methods were previously described (Sehn et al. J Clin Oncol 2020). Pts in the Ext cohort received Pola+BR with the same dosing regimen (Pola 1.8mg/kg IV with each cycle of BR). The primary endpoint was IRC-assessed CR at primary response assessment [PRA] by PET-CT (modified Lugano criteria). Secondary endpoints included objective response rate (ORR), best objective response (BOR), OS, PFS, duration of response (DOR), and safety. Results: As of January 2, 2020, median follow-up for pts treated with Pola+BR was 56.1 mo in the safety run-in cohort (N=6), 42.9 mo in the randomized arm (N=40), and 9.7 mo for the Ext cohort (N=106). Baseline characteristics (Table 1) were largely similar between the randomized Pola+BR arm and the Ext cohort. Updated survival data from the randomized cohort (Pola+BR vs BR) showed the median IRC-assessed PFS (95% confidence interval [CI]) was 9.2 (6.0-13.0) vs 3.7 (2.1-4.5) mo (hazard ratio [HR] 0.4; 95% CI: 0.2-0.7); median OS (95% CI) was 12.4 (9.0-32.0) vs 4.7 (3.7-8.3) mo (HR 0.4; 95% CI: 0.2-0.7), respectively (Figure). In the Pola+BR arm, 6 pts (15%) had an IRC-assessed DOR of >2