Phase 2 data from ROSETTA Lung-02, a global randomized phase 2/3 trial of pumitamig (PD-L1 × VEGF-A bsAb) + chemotherapy in 1L NSCLC.

Abstract

8513 Background: Pumitamig (BNT327/BMS986545) is an investigational PD-L1 × VEGF-A bsAb designed to restore effector T-cell function by binding PD-L1 and localizing VEGF-A neutralization within the tumor microenvironment. We present the prespecified interim analysis of the Phase 2 dose-optimization part of the global Phase 2/3 ROSETTA Lung-02 trial (NCT06712316) evaluating the recommended Phase 3 dose of pumitamig + chemotherapy in 1L NSCLC. Methods: The Phase 2 part of ROSETTA Lung-02 enrolled pts with treatment-naïve advanced NSCLC, no actionable genomic alterations, regardless of PD-L1 status, ECOG PS ≤1, and ≥1 measurable lesion per RECIST v1.1 into two substudies based on histology (nonsquamous [NSQ] and squamous [SQ]). Pts were randomized 1:1 to 1400 mg (dose level [DL] 1) or 2000 mg (DL2) pumitamig + histology-specific chemotherapy Q3W (NSQ: carboplatin + pemetrexed; SQ: carboplatin + paclitaxel). Primary endpoints were safety, overall response rate (ORR), and best percentage change in tumor size from baseline. Key secondary endpoints include duration of response (DOR) and disease control rate (DCR). Results: The Phase 2 part enrolled 44 pts (NSQ n=23; SQ n=21; data cutoff Nov 21, 2025). Median age was 66 y (range: 41–87), and 27 (61.4%) pts had ECOG PS 1. Among 40 response-evaluable pts, best overall response was CR in 2 pts, PR in 26, and SD in 12, for an ORR of 70.0% (28/40; confirmed ORR was 52.5% [21/40], 5 pending confirmation) and DCR of 100%. DOR data were not mature at the time of data cutoff. Median best change in tumor volume was -38.2% (NSQ -36.6%; SQ -39.7%). In NSQ NSCLC, ORR was 66.7% (14/21) and, by pumitamig dose, it was 72.7% for DL1 (8/11) and 60.0% for DL2 (6/10). In SQ NSCLC, ORR was 73.7% (14/19), 81.8% for DL1 (9/11) and 62.5% for DL2 (5/8). Central PD-L1 levels were available for 35 pts (PD-L1 <1% [n=20], 1–49% [n=9], ≥50% [n=6]), with activity across PD-L1 levels. Circulating tumor DNA dynamics were assessed. Median treatment duration was 4.5 mo (range: 0.1–8.8) with 30 (69.8%) pts still on treatment. In the safety set (N=43), 40 (93.0%) pts had a treatment-related adverse event (TRAE). Grade ≥3 TRAEs were reported in 19 (44.2%) pts and were considered pumitamig-related in 8 (18.6%). Pumitamig-related TRAEs led to treatment discontinuation in 2 (4.7%) pts. Immune-related AEs (irAEs) occurred in 6 (14.0%) pts and grade ≥3 irAEs in 1 (2.3%). Bleeding events were reported in 7 (16.3%) pts, with only 1 event being grade 3. Conclusions: In these first global data for a PD-(L)1 × VEGF-A bsAb in 1L NSCLC regardless of PD-L1 status, pumitamig + chemotherapy showed encouraging efficacy with a manageable safety profile. Efficacy of the lower dose + chemotherapy was particularly encouraging (ORR 72.7% in NSQ, 81.8% in SQ) and is being evaluated vs pembrolizumab + chemotherapy in the ongoing Phase 3 part of the trial. Clinical trial information: NCT06712316 .