Abstract P120

KEYNOTE-B68: Updated efficacy and safety of pembrolizumab every six weeks in relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) or primary mediastinal B-cell lymphoma (PMBCL)

Background: Pembrolizumab (pembro) 200 mg Q3W is approved by the FDA to treat R/R cHL and R/R PMBCL. Recently, the FDA gave accelerated approval of pembro 400 mg Q6W in all approved indications based on data in solid tumors. The Phase 2 KEYNOTE-B68 trial (NCT04875195) evaluates efficacy and safety of pembro 400 mg Q6W in patients (pts) with R/R cHL or R/R PMBCL. We previously reported ORR of 65% in R/R cHL, and 50% in R/R PMBCL with approximately 9 months (mo) of follow-up. Here we present data from 66 pts with approximately 16 mo of follow-up.

Methods: In this nonrandomized trial, pts aged ≥18 years with anti-PD-1/PD-L1 naïve R/R cHL or R/R PMBCL received 400 mg pembro Q6W for ≤ 18 cycles, until progression, 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. Primary endpoint was ORR (Lugano by INV). Secondary endpoints were DOR (Lugano by INV) and safety. Exploratory endpoints were PFS (Lugano by INV) and OS.

Results: At data cut-off (May 15, 2023), 66 pts (60 R/R cHL, 6 R/R PMBCL) were enrolled. Median follow-up was 15.7 mo for R/R cHL and 17.5 mo for R/R PMBCL. ORR was 66.7% (95% CI, 53.3 -78.3 [35.0% CR; 31.7% PR]) for R/R cHL, and 50% (95% CI, 11.8 -88.2 [33.3% CR; 16.7% PR]) for R/R PMBCL. Median DOR was 16.6 mo for R/R cHL and 9.7 mo for R/R PMBCL (Table). Treatment-related AEs occurred in 26 pts with R/R cHL and 2 with R/R PMBCL. Grade 3-4 treatment-related AEs occurred in 3 (5%) pts with R/R cHL and 1 (17%) with R/R PMBCL. Immune-mediated AEs occurred in 14 (23%) pts with R/R cHL and 1 (17%) with R/R PMBCL. Grade 3 infusion-related reactions and immune-mediated AEs occurred in 2 (3%) pts and 1 (2%) pt, respectively, with R/R cHL. No grade ≥4 immune-mediated AEs occurred in pts with R/R cHL and no grade ≥3 immune-mediated AEs occurred in pts with R/R PMBCL.

Conclusions: With approximately 16 mo of follow-up, ORR and PFS in pts with R/R cHL increased, further highlighting the consistency to pembro 200 mg Q3W. No new safety concerns occurred in pts with cHL or PMBCL. This trial further demonstrates the continued antitumor activity in pts and confirms the acceptability of Q6W dosing in heme indications.