Pumitamig Plus Chemotherapy Shows High Response Rates Across PD-L1 Levels and NSCLC Subtypes in Phase 2 ROSETTA Lung-02 Interim Analysis

BioNTech and Bristol Myers Squibb presented interim phase 2 data from the global ROSETTA Lung-02 trial (NCT06712316) at the 2026 American Society of Clinical Oncology Annual Meeting on May 30, 2026. The data show that pumitamig, an investigational programmed cell death protein-1 (PD-L1)× vascular endothelial growth factor A (VEGF-A) bispecific immunomodulator, in combination with chemotherapy produced high confirmed objective response rates (cORR) across both histologic subtypes and all evaluated PD-L1 expression levels in previously untreated advanced non-small cell lung cancer (NSCLC). The data represent the first global phase 2 results for a PD-(L)1×VEGF bispecific agent in combination with chemotherapy in first-line NSCLC, according to the companies.¹

“Despite significant immuno-oncology advances in the treatment of non-small cell lung cancer, most advanced diseases relapse on or after a PD-(L)1 checkpoint inhibitor treatment,² indicating that targeting this immunologic pathway alone is insufficient to achieve durable responses,” said Solange Peters, MD, PhD, lead investigator and director of Oncology at the University Hospital of Lausanne, Switzerland, in a company press release.¹ “I am encouraged by the efficacy signal with this bispecific approach, showing robust responses across subtypes and PD-L1 levels, supporting the continued investigation of pumitamig and its potential to deliver improved outcomes for a broad range of patients with NSCLC.”

What did the ROSETTA Lung-02 phase 2 trial design and interim efficacy data show?

The phase 2 dose-optimization portion of ROSETTA Lung-02 randomized patients 1:1 to pumitamig 1400 mg or 2000 mg plus histology-specific chemotherapy every three weeks, with carboplatin plus pemetrexed for non-squamous disease and carboplatin plus paclitaxel for squamous disease, in patients without actionable genomic alterations and with any PD-L1 expression level. At the April 13, 2026 data cutoff, among 40 response-evaluable patients with a median follow-up of 9.0 months, the confirmed objective response rate (cORR) was 57.1% in non-squamous and 68.4% in squamous NSCLC, with a disease control rate of 100% across both subtypes.

At the lower 1400 mg dose, cORRs were 63.6% and 72.7% in non-squamous and squamous NSCLC, respectively. Response rates stratified by PD-L1 tumor proportion score were 47.6% (TPS <1%), 77.8% (TPS 1–49%), and 100% (TPS ≥50%). Based on the totality of phase 2 data, a 1500 mg flat dose every three weeks was selected for the phase 3 portion of the trial, which will compare pumitamig plus chemotherapy against pembrolizumab plus chemotherapy, with progression-free survival by blinded independent central review as the primary endpoint.

Why does simultaneous PD-L1 and VEGF-A blockade represent a clinically meaningful strategy in NSCLC?

PD-(L)1 checkpoint inhibitors have transformed first-line NSCLC management, yet most patients with advanced disease ultimately progress on or after checkpoint inhibitor-based therapy, underscoring the insufficiency of immune checkpoint blockade alone for durable disease control.³ VEGF-A promotes an immunosuppressive tumor microenvironment through multiple mechanisms, including inhibition of dendritic cell maturation and T-cell trafficking. Anti-angiogenic agents have demonstrated additive effects when combined with immunotherapy in select tumor types.⁴

Pumitamig is designed to anchor to PD-L1 on tumor cells, localizing VEGF-A blockade within the tumor microenvironment. This mechanism is intended to enhance antitumor activity while limiting systemic anti-angiogenic exposure. More than 2000 patients have been treated with pumitamig across clinical trials to date.¹

How broad is pumitamig's ongoing clinical development program across tumor types?

Seven global phase 3 trials with registrational potential are currently ongoing, spanning first-line SCLC (ROSETTA Lung-01), unresectable stage III NSCLC (ROSETTA Lung-201, comparing pumitamig to durvalumab following chemoradiation), first-line PD-L1 ≥50% NSCLC (ROSETTA Lung-202, comparing pumitamig to pembrolizumab), first-line triple-negative breast cancer, first-line microsatellite stable colorectal cancer, and first-line gastric cancer. Pumitamig is additionally being investigated in more than 10 novel-combination trials with antibody-drug conjugates and other modalities.¹

What limitations apply to these phase 2 findings, and what data will be needed to establish clinical utility?

The interim analysis, based on 40 response-evaluable patients with a median follow-up of 9.0 months, represents a sample size insufficient to draw conclusions about survival outcomes or long-term durability of response. Confirmed ORR is a surrogate endpoint, and progression-free and overall survival data from the phase 3 trial will be required to determine whether pumitamig improves outcomes over the current pembrolizumab-plus-chemotherapy standard of care.⁵

The 100% cORR observed in the TPS ≥50% subgroup reflects a very small patient subset and should be interpreted with caution. Duration of response and disease control data beyond the current follow-up window remain immature.

References

1. Bristol Myers Squibb. Global data for BioNTech and Bristol Myers Squibb’s PD-L1xVEGF-A bispecific pumitamig shows encouraging efficacy in patients with non-small cell lung cancer in ROSETTA Lung-02 trial. Published May 30, 2026. Accessed June 1, 2026. https://news.bms.com/news/corporate-financial/2026/Global-Data-for-BioNTech-and-Bristol-Myers-Squibbs-PD-L1xVEGF-A-Bispecific-Pumitamig-Shows-Encouraging-Efficacy-in-Patients-with-Non-Small-Cell-Lung-Cancer-in-ROSETTA-Lung-02-Trial-2026-TW53rMYYjx/default.aspx
2. Mariniello A, Borgeaud M, Weiner M, et al. Primary and acquired resistance to immunotherapy with checkpoint inhibitors in NSCLC: From bedside to bench and back. BioDrugs. 2025;39(2):215-235. doi:10.1007/s40259-024-00700-2
3. Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer. N Engl J Med. 2016;375(19):1823-1833. doi:10.1056/NEJMoa1606774
4. Socinski MA, Jotte RM, Cappuzzo F, et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018;378(24):2288-2301. doi:10.1056/NEJMoa1716948
5. Paz-Ares L, Ciuleanu TE, Cobo M, et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(2):198-211. doi:10.1016/s1470-2045(20)30641-0