Efficacy and safety of pembrolizumab every six weeks in relapsed/refractory classical Hodgkin lymphoma or primary mediastinal B-cell lymphoma: The phase 2 KEYNOTE-B68 trial.

Abstract

7517 Background: Pembrolizumab (pembro) 200 mg Q3W demonstrated robust antitumor activity and manageable safety in relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) and R/R primary mediastinal B-cell lymphoma (PMBCL), resulting in FDA approval. Recently, the FDA granted accelerated approval of pembro 400 mg Q6W in all approved indications based on data from solid tumor trials in solid tumors. The global Phase 2 trial (NCT04875195) evaluates the efficacy and safety of pembro 400 mg Q6W in R/R cHL and R/R PMBCL. We present, for the first time, data from 66 patients (pts) with approximately 9 months (mo) of follow up. Methods: In this nonrandomized, open-label trial, pts aged ≥18 years with PD-1 inhibitor naïve R/R cHL or PMBCL received 400 mg pembro Q6W for ≤ 18 cycles, until progression, unacceptable toxicity, or withdrawal. Eligible pts with cHL must have relapsed or failed to respond after ≥1 prior lines of therapy (LOT) or relapsed or failed to respond after ≥1 prior multiagent LOT or autologous stem cell transplant (ASCT). Eligible pts with PMBCL must have relapsed or failed to respond after ≥2 prior LOT including rituximab and relapsed or failed to respond to or were ineligible for ASCT. The primary endpoint was ORR per Lugano criteria by investigator (Lugano, INV). Secondary endpoints were DOR (Lugano, INV) and safety. Exploratory endpoints were PFS (Lugano, INV) and OS. Data cut-off date was October 18, 2022. Results: At data cut-off, 66 pts (60 R/R cHL, 6 R/R PMBCL) were enrolled. Median follow-up (range) was 8.9 mo (1 – 15.9) for pts with R/R cHL and 10.6 mo (5.1 – 15.4) with R/R PMBCL. The ORR was 65% (95% CI, 51.6 – 76.9 [33.3% CR; 31.7% PR]) for pts with R/R cHL, and 50% (95% CI, 11.8 – 88.2 [33.3% CR; 16.7% PR]) for R/R PMBCL. Drug-related adverse events (AE) occurred in 24 pts (40%) with R/R cHL and 2 pts (33.3%) with R/R PMBCL. Grade ≥3 drug-related AEs occurred in 3 pts (5%) with R/R cHL and 1 pt (16.7%) with R/R PMBCL. Immune-mediated AEs occurred in 13 pts (21.7%) with R/R cHL and 1 pt (16.7%) with R/R PMBCL. Grade ≥3 immune-mediated AEs occurred in 2 pts (3.3%) with R/R cHL. Antitumor activity is summarized in the Table. Conclusions: With approximately 9 mo of follow up, pembro 400 mg Q6W demonstrates robust antitumor activity in pts with R/R cHL and R/R PMBCL. The ORR observed is similar to pembro 200 mg Q3W in R/R cHL and R/R PMBCL. Pembro 400 mg Q6W had no new safety concerns, confirming Q6W dosing in hematologic indications. Clinical trial information: NCT04875195 . [Table: see text]