Pumitamig Shows Positive Trend in PFS Treating Patients With ES-SCLC

Pumitamig (BNT327, BMS986545; Bristol Myers Squibb, BioNTech), an investigational bispecific antibody that targets PD-L1 x VEGF-A, demonstrated encouraging antitumor responses with a positive trend in progression free survival (PFS), according to an abstract presented at the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer in Barcelona, Spain.

The data are from a global, randomized phase 2 clinical trial (NCT06449209) that assessed 2 dose levels of pumitamig in combination with other therapies when treating patients with extensive stage small cell lung cancer (ES-SCLC).^1,2

Pumitamig is a novel investigational bispecific antibody that combines 2 complementary, validated mechanisms in oncology into 1 single molecule. It blocks VEGF-A to reverse the tumor’s immunosuppressive effect in its microenvironment and cuts off the blood and oxygen supply that feeds tumor cells (antiangiogenesis effect) with the intention of preventing the tumor from growing and proliferating. 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.¹

“SCLC 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. While approximately [60% to 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,” John V. Heymach, MD, lead investigator and chair of thoracic/head and neck medical oncology at University of Texas MD Anderson Cancer Center, said in a news release.¹

The global randomized, open-label, parallel group phase 2 clinical trial, BNT327-01, evaluated pumitamig in patients with untreated ES-SCLC (cohort 1) or SCLC who progressed on first- or second-line treatment (cohort 2 and cohort 3). In Cohort 1, patients received pumitamig in 2 dose levels with chemotherapy for 4 cycles, followed by pumitamig maintenance for up to 2 years or until disease progression or unacceptable toxicity to identify an optimized dose for future clinical investigation. Cohorts 2 and 3 explored the combination of 2 dose levels of pumitamig plus paclitaxel or topotecan in the second- or third-line setting.^1-3

The coprimary end points of the trial were objective response rate (ORR), change in tumor size and early tumor shrinkage, and safety. Secondary end points include duration of response (DOR), disease control rate (DCR), PFS, and overall survival (OS).^1-3

The interim analysis included 43 patients with untreated ES-SCLC (cohort 1) who received pumitamig in combination with standard of care chemotherapy in 2 dose levels. At the Aug. 7, 2025, data cut-off, among the 38 efficacy-evaluable patients, the confirmed ORR was approximately 76.3% (85.0% and 66.7% at 20 and 30 mg/kg dose levels, respectively) and the DCR was 100%. The mean best percentage change in tumor size showed a tumor shrinkage of approximately 56.7%, with 89.5% of patients achieving early tumor shrinkage. Median PFS was 6.8 months (6.3 and 7.0 months at 20 and 30 mg/kg doses, respectively), with median OS not being mature at the time of the analysis.^1,3

“The response rate and early PFS 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 antitumor responses relative to current standard of care,” Heymach said.¹

Pumitamig plus chemotherapy notably showed a manageable safety profile, with no new safety signals beyond those typically described for chemotherapy agents and anti-PD-L1 and anti-VEGF monotherapies, and a discontinuation rate of only 14%. Out of the 43 patients, treatment-emergent AEs related to pumitamig that were grades 3 or higher were reported by 1 patient at the lower dose level, and 5 patients at the higher dose.^1,3

“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 2 fundamental drivers of small cell lung cancer in one single molecule,” Özlem Türeci, MD, cofounder and chief medical officer at BioNTech, said in the news 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 SCLC but also across other difficult-to-treat solid tumors. These interim data for pumitamig represent an important step in the right direction.”¹

There are over 20 clinical trials currently ongoing or planned to evaluate pumitamig either as a monotherapy or in combination with other treatment modalities targeting different oncogenic pathways in more than 10 solid tumor indications. Multiple global trials are ongoing or planned to start in 2025, according to the news release from the manufacturer.¹

“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,” Bryan Campbell, senior vice president and lead of program leadership, hematology, oncology, cell therapy at Bristol Myers Squibb, said in the news release. “These are the first-ever data in a global population in advanced SCLC 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. 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.”¹

REFERENCES

1. Bristol Myers Squibb. 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. News release. September 8, 2025. Accessed September 25, 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

2. Safety, Preliminary Effectiveness of BNT327, an Investigational Therapy for Patients With Small-cell Lung Cancer in Combination With Chemotherapy. ClinicalTrials.gov identifier: NCT06449209. Updated September 19, 2025. Accessed September 25, 2025. https://clinicaltrials.gov/study/NCT06449209

3. Heymach JV, Cho BC, Sezer A, et al. Global Phase 2 Randomized Trial of BNT327 (Pumitamig; PD-L1 x VEGF-A bsAb) + Chemotherapy for 1L ES-SCLC: Dose Optimization Analysis. Presented at: International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer. Barcelona, Spain. September 6–9, 2025.