BioNTech and Bristol Myers Squibb announced encouraging interim results from their global Phase 2 trial evaluating pumitamig (BNT327/BMS986545), a novel bispecific antibody targeting PD-L1 and VEGF-A, in combination with chemotherapy for patients with extensive-stage small cell lung cancer (ES-SCLC). The data, presented at the IASLC 2025 World Conference on Lung Cancer in Barcelona, showed promising antitumor activity and support the drug's potential to establish a new standard of care.
Strong Efficacy Signals in Aggressive Cancer
The interim analysis included 43 patients with untreated extensive-stage small cell lung cancer who received pumitamig in combination with standard chemotherapy at two dose levels. Among 38 efficacy-evaluable patients at the August 7, 2025 data cut-off, the confirmed overall response rate reached 76.3%, with 85.0% response at the 20 mg/kg dose level and 66.7% at the 30 mg/kg dose level. Notably, the disease control rate was 100% across all patients.
The treatment demonstrated substantial tumor shrinkage, with a mean best percentage change in tumor size of 56.7% and 89.5% of patients achieving early tumor shrinkage. Median progression-free survival was 6.8 months (6.3 months at 20 mg/kg and 7.0 months at 30 mg/kg), while overall survival data remained immature at the time of analysis.
"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," 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.
Manageable Safety Profile
Pumitamig plus chemotherapy demonstrated a manageable safety profile with no new safety signals beyond those typically associated with chemotherapy agents and anti-PD-(L)1 and anti-VEGF monotherapies. The discontinuation rate was only 14%. Among 43 patients, pumitamig-related treatment-emergent adverse events of Grade ≥3 were reported in one patient at dose level 1 and five patients at dose level 2.
Addressing Critical Unmet Need
Small cell lung cancer represents one of the most challenging malignancies, accounting for 15% of all lung cancer cases with an estimated 250,000 new cases globally per year. The disease is characterized by rapid growth, poor prognosis, and a 5-year relative survival rate of just 5% in advanced stages. While approximately 60-70% of patients initially respond to current standard of care treatments, most progress within months after treatment.
"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," Heymach noted. "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."
Novel Dual-Target Approach
Pumitamig represents a novel investigational bispecific antibody that combines two complementary, validated mechanisms in oncology into a single molecule. The drug combines PD-L1 checkpoint inhibition aimed at restoring T cells' ability to recognize and destroy tumor cells with the neutralization of VEGF-A. The blocking of VEGF-A is designed to reverse the tumor's immuno-suppressive effect in its microenvironment and cut off the blood and oxygen supply that feeds tumor cells.
"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 Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech.
The drug may be differentiated through its mechanism 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.
Advancing to Phase 3 Development
The interim results confirm dose selection for the ongoing global pivotal Phase 3 ROSETTA-LUNG-01 trial (NCT06712355), which is evaluating pumitamig plus chemotherapy versus atezolizumab plus chemotherapy as first-line treatment in patients with untreated ES-SCLC. The pivotal 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 globally.
"These are the first-ever data in a global population in advanced small cell lung cancer for a PD-(L)1 x VEGF bispecific antibody, supporting a possible new standard of care for patients with extensive-stage small cell lung cancer," said Bryan Campbell, Senior Vice President, Head of Program Leadership, Hematology, Oncology, Cell Therapy at Bristol Myers Squibb.
Broad Development Program
More than 1,200 patients have been treated with pumitamig in clinical trials to date. More than 20 clinical trials are currently ongoing or planned to evaluate pumitamig either as monotherapy or in combination with other treatment modalities across more than 10 solid tumor indications. Multiple global trials are ongoing or planned to start in 2025, including three global clinical trials with registrational potential evaluating pumitamig plus chemotherapy compared to standard of care treatments in first-line small cell lung cancer, first-line non-small cell lung cancer (ROSETTA LUNG-02), and first-line triple-negative breast cancer (ROSETTA BREAST-01).
Pumitamig received Orphan Drug designation from the U.S. Food and Drug Administration for the treatment of patients with small cell lung cancer in 2025, reflecting the significant unmet medical need in this indication.
