Phase 2 trial of brentuximab vedotin (BV) with pembrolizumab (pembro) in patients with previously treated metastatic non-small cell lung cancer (NSCLC) or cutaneous melanoma (SGN35-033): Overall survival.

Abstract

2617 Background: BV, a CD30 directed antibody-drug conjugate, may selectively deplete a subset of regulatory T-cells (Tregs) that express CD30 and re-sensitize tumors to anti-PD-1 therapy. This ongoing, multi-cohort, multicenter, open-label trial evaluating the efficacy and safety of BV+pembro in patients (pts) with anti-PD-1 refractory solid tumors previously reported an ORR (8-22%), DCR (67-80%), and CD8+T cell infiltration in on-treatment biopsies of responders (Lee, SITC 2023). Here we report OS and biomarker analyses. Methods: Pts with primary refractory (progression without response or SD for < 6 months) or secondary refractory (progression after response for ≥3 months or SD for ≥6 months) NSCLC or melanoma who progressed on anti-PD-1 therapy were included. Pts received BV (1.8 mg/kg) and pembro (200 mg) every 21 days. The primary endpoint was confirmed ORR. Exploratory endpoints included OS and biomarker analyses of blood and tumor samples. Results: 55 pts with NSCLC and 58 pts with melanoma were dosed (86% white, 63% male; 57% ≥ age 65 yrs). Pts received 3 median prior lines of therapy (as previously reported). Investigator-assessed response was measured according to RECIST v1.1. At a median follow up of 17.2 months, median OS (mOS) was 13.9 months (NSCLC) and 12.9 months (melanoma) (Table 1). The estimated probability of survival (Kaplan-Meier) at 12 months was 54.0% (95% CI 43.69, 63.22) for the study population. Immune mediated AEs were reported in 25% of pts, Grade ≥3 TEAEs in 56%, TESAEs in 42%, and TE peripheral neuropathy (SMQ) in 48% of pts. 17% of pts discontinued treatment due to TEAEs. No new safety signals were identified and no deaths due to treatment-related AEs were reported. Paired tumor biopsies from 19 pts showed increased CD8+T cell infiltration in 11 pts. Conclusions: These data support the immunomodulatory capacity of BV with pembro. This combination shows encouraging OS data in pts with solid tumors who have progressed on anti-PD-1 therapy. The safety profile is comparable to previously reported data. The study remains ongoing. Clinical trial information: NCT04609566 . [Table: see text]