News|Articles|September 10, 2025

Investigational PD-L1 x VEGF-A Bispecific Antibody Demonstrates Strong Overall Response Rate in Phase II Small Cell Lung Cancer Trial

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Key Takeaways

Pumitamig demonstrated a 76.3% objective response rate and 100% disease control rate in ES-SCLC patients, with significant tumor shrinkage.
The trial's primary endpoints included objective response rate, tumor size change, early tumor shrinkage, and safety, with secondary endpoints focusing on duration of response and overall survival.
Safety findings were consistent with known chemotherapy and PD-L1/VEGF therapies, showing a low discontinuation rate and few severe treatment-related adverse events.
Pumitamig represents a potential new standard of care for ES-SCLC, addressing the need for more effective treatments in this aggressive cancer type.

Results from a Phase II trial (NCT06449209) showed that BioNTech’s and Bristol Myers Squibb’s pumitamig in combination with standard chemotherapy demonstrated encouraging anti-tumor activity in patients with extensive-stage small cell lung cancer.

Topline Findings

Encouraging Anti-Tumor Activity: In a Phase II trial (NCT06449209), pumitamig (BNT327/BMS986545) demonstrated high overall response rates and substantial tumor shrinkage in patients with extensive-stage small cell lung cancer (ES-SCLC).

Potential New Treatment Option: Pumitamig targets both PD-L1 and VEGF-A, offering a novel dual-mechanism approach that could improve outcomes in this aggressive and hard-to-treat lung cancer.

Global Development and Expansion: The therapy is advancing into a pivotal Phase III trial (ROSETTA-LUNG-01) and has received FDA Orphan Drug designation, highlighting its potential as a future standard of care for ES-SCLC.

Results from a Phase II trial (NCT06449209) showed that BioNTech’s and Bristol Myers Squibb’s (BMS) pumitamig (BNT327/BMS986545) demonstrated encouraging anti-tumor activity in patients with extensive-stage small cell lung cancer (ES-SCLC). According to the company, pumitamig represents a promising potential new treatment option for patients with this aggressive form of lung cancer, highlighting its potential to improve outcomes where current therapies remain limited.¹

Could Pumitamig Offer a new Approach for Durable Responses in ES-SCLC?

“Small cell lung cancer is the most aggressive type of lung cancer with rapid growth, a poor prognosis and 5-year relative survival rate of just 5% in advanced stages,” said lead investigator trial John V. Heymach, MD, chair of thoracic/head and neck medical oncology, University of Texas MD Anderson Cancer Center, in a press release. “While approximately 60%-70% of patients initially respond to current standard of care treatments, most progress within months after treatment signifying an urgent need for new treatment options which improve outcomes. 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.”

Key Trial Details

The global, randomized, open-label, parallel group trial evaluated pumitamig in approximately 110 patients with ES-SCLC or SCLC who progressed on first- or second-line treatment.
Patients in cohort 1, which consisted of the former, received pumitamig in two dose levels in addition to chemotherapy for four cycles. From there, they received pumitamig maintenance for up to two years.
Patients in cohorts 2 and 3 explored two dose levels of pumitamig in combination with either paclitaxel or topotecan for patients in the second- or third-line treatment setting.
The primary endpoints of the trial were objective response rate (ORR), change in tumor size and early tumor shrinkage, and safety.
Key secondary endpoints included duration of response (DoR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS).
Results showed that the confirmed ORR was 76.3%, with a disease control rate of 100% and a mean tumor shrinkage of 56.7%.
Early tumor shrinkage was observed in 89.5% of patients, and median PFS ranged from 6.3 months to seven months across dose levels.
Safety findings were consistent with known profiles of chemotherapy and PD-L1/VEGF therapies, with a low discontinuation rate of 14% and few grade ≥3 treatment-related adverse events.²

Expert Perspectives

“Every innovation we pursue starts with the needs of patients. These interim data for pumitamig presented today show encouraging signals for our science-driven approach to address two fundamental drivers of small cell lung cancer in one single molecule,” said Özlem Türeci, MD, co-founder, chief medical officer, BioNTech, in the press release. “Our ultimate goal is to translate science into meaningful survival benefits for many patients by overcoming some of the biggest treatment challenges, not only in small cell lung cancer but also across other difficult-to-treat solid tumors. These interim data for pumitamig represent an important step in the right direction.”

According to the American Cancer Society, SCLC accounts for approximately 13% of all lung cancer cases, making it significantly less common than non-small cell lung cancer. Lung cancer is the second most common form of the disease in the United States for both men and women.³

“Today’s data add to the growing body of evidence indicating the potential of pumitamig to improve outcomes across a wide range of solid tumors,” said Bryan Campbell, SVP, head, program leadership, hematology, oncology, cell therapy at BMS, in the press release. “These are the first-ever data in a global population in advanced small cell lung cancer for a PD-L1 x VEGF bispecific antibody, supporting a possible new standard of care for patients with extensive-stage small cell lung cancer. We look forward to continuing to jointly advance research and development of pumitamig as a potential new treatment option with meaningful clinical benefit for patients in need.”

References

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 Small Cell Lung Cancer Shows Encouraging Antitumor Activity. BMS. September 8, 2025. Accessed September 9, 2025. https://news.bms.com/news/corporate-financial/2025/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-Small-Cell-Lung-Cancer-Shows-Encouraging-Antitumor-Activity/default.aspx
Safety, Preliminary Effectiveness of BNT327, an Investigational Therapy for Patients With Small-cell Lung Cancer in Combination With Chemotherapy. Clinicaltrials.gov. Accessed September 9, 2025. https://clinicaltrials.gov/study/NCT06449209?term=NCT06449209&rank=1
Key Statistics for Lung Cancer. American Cancer Society. Accessed September 9, 2025. https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html

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