Results from a phase 1b study of blinatumomab-pembrolizumab combination in adults with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

e19584 Background: This open-label, multicenter, phase 1b study evaluated the safety and efficacy of blinatumomab and pembrolizumab combination therapy in patients (pts) with R/R DLBCL (NCT03340766). Methods: Key inclusion criteria included adults with ECOG performance status ≤2 and life expectancy ≥12 weeks. In cycle 1, pts received a continuous intravenous (cIV) infusion of blinatumomab followed by step dosing to the target dose (TD; Table). After a 28-day treatment-free interval, cIV infusion of blinatumomab was administered for 28 days in cycle 2 with the same dose escalations as in cycle 1. Pembrolizumab 200 mg IV was administered once every 21 days starting on day 15 in cohort 1a, and on day 19 in cohorts 2a and 3a. Pts were premedicated with dexamethasone. Dose-limiting toxicities (DLT) were the primary endpoint. The maximum tolerated dose (MTD) was the highest dose level at which ≤1 of 6 or ≤2 of 10 pts experienced a DLT. Results: As of June 10, 2021, 31 pts were enrolled in cohorts 1a, 2a, and 3a (Table). DLTs occurred in 1 (10%) pt in cohort 1a (neutropenia) and 2 (40%) pts in cohort 3a (cognitive impairment, and elevated AST, ALP, and GGT levels). Treatment-emergent (TE) adverse events (AEs) were observed in 31 (100%) pts; grade ≥3 AEs occurred in 29 (94%) pts. The most frequent grade ≥3 TEAE attributed to blinatumomab was nervous system disorders (11 [35%]) and that attributed to pembrolizumab was blood and lymphatic system disorders (5 [16%]). Serious blinatumomab-related and pembrolizumab-related AEs were observed in 15 (48%) and 2 (6%) pts, respectively. Fourteen (45%) deaths occurred; none were treatment-related. Cohort 2a dose was determined as the MTD (Table). In cohort 2a, the objective response rate within 12 weeks of blinatumomab treatment was 30%; the median duration of response in responders (n = 8) was 176.5 (range: 28–680) days. Exposures of blinatumomab and pembrolizumab in this combination study were consistent with historical data for the individual agents. Conclusions: The cohort 2a dosing schedule with TD of 56 μg/day of blinatumomab was established as the MTD. The study was terminated after dose finding because the MTD of blinatumomab in combination with pembrolizumab was lower than the MTD of blinatumomab monotherapy, with no apparent efficacy gain. Clinical trial information: NCT03340766. [Table: see text]