Pumitamig Plus Chemotherapy Shows Encouraging Antitumor Activity in ES-SCLC Patients.

A bispecific antibody, pumitamig (BNT327/BMS986545), combined with chemotherapy has shown promising results in treating extensive-stage small cell lung cancer (ES-SCLC). Global interim Phase 2 data revealed a 76.3% confirmed objective response rate, 100% disease control rate, and a median progression-free survival of 6.8 months. The trial's findings support the ongoing global pivotal Phase 3 ROSETTA LUNG-01 trial, aiming to establish pumitamig as a standard of care for first-line ES-SCLC treatment. The combination therapy was found to have a manageable safety profile.

A global interim Phase 2 trial evaluating pumitamig (BNT327/BMS986545), a bispecific antibody targeting PD-L1 x VEGF-A, in combination with chemotherapy for extensive-stage small cell lung cancer (ES-SCLC) has shown encouraging results. The trial, conducted by BioNTech and Bristol Myers Squibb, reported a 76.3% confirmed objective response rate (cORR), 100% disease control rate (DCR), and a median progression-free survival (mPFS) of 6.8 months. These findings support the ongoing global pivotal Phase 3 ROSETTA LUNG-01 trial, which aims to establish pumitamig as a potential new standard of care for first-line ES-SCLC treatment.

The interim analysis included 43 patients with untreated extensive-stage small cell lung cancer who received pumitamig in combination with standard of care chemotherapy in two dose levels. Among 38 efficacy-evaluable patients, the confirmed overall response rate was 76.3% (85.0% at 20 mg/kg and 66.7% at 30 mg/kg), and the disease control rate (DCR) was 100%. The mean best percentage change in tumor size showed a tumor shrinkage of 56.7%, with 89.5% of patients achieving early tumor shrinkage. Median progression-free survival (mPFS) was 6.8 months (6.3 months at 20 mg/kg and 7.0 months at 30 mg/kg), with mOS not being mature at the time of the analysis. Pumitamig plus chemotherapy showed a manageable safety profile, with no new safety signals beyond those typically described for chemotherapy agents and anti-PD-(L)1 and anti-VEGF monotherapies, and a discontinuation rate of 14%.

The data were presented as a late-breaker oral presentation at the IASLC 2025 World Conference on Lung Cancer in Barcelona. "Small cell lung cancer is the most aggressive type of lung cancer with rapid growth, a poor prognosis, and a 5-year relative survival rate of just 5% in advanced stages," said John V. Heymach, M.D., Lead Investigator and Chair of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center. "The response rate and early progression-free survival we are seeing in this interim analysis are encouraging and merit further investigation in a larger trial to validate pumitamig’s potential to offer patients more durable anti-tumor responses relative to current standard of care."

Pumitamig is an investigational bispecific antibody that combines PD-L1 checkpoint inhibition and VEGF-A neutralization. The blocking of VEGF-A aims to reverse the tumor’s immunosuppressive effect in its microenvironment and cut off the blood and oxygen supply that feeds tumor cells. Pumitamig may be differentiated via its mechanism of action of targeting PD-L1 on tumor cells to localize anti-VEGF activity within the tumor microenvironment, aiming to enhance therapeutic precision and minimize systemic exposure.

The ongoing global pivotal Phase 3 ROSETTA LUNG-01 trial is evaluating pumitamig plus chemotherapy versus atezolizumab plus chemotherapy as a first-line treatment in patients with untreated ES-SCLC. The trial is enrolling patients at clinical trial sites in the United States, the United Kingdom, Türkiye, China, the Republic of Korea, and Australia, with additional sites planned to open globally.

References:
[1] https://www.globenewswire.com/news-release/2025/09/08/3146265/0/en/First-Disclosure-of-Global-Interim-Phase-2-Data-for-BioNTech-and-Bristol-Myers-Squibb-PD-L1xVEGF-A-Bispecific-Antibody-Pumitamig-BNT327-BMS986545-in-Patients-with-Extensive-Stage-S.html