|
BioNTech SE, a global next generation immunotherapy company, and Bristol Myers Squibb Company, a global biopharmaceutical company, presented interim data from a global randomized phase 2 trial (NCT06449209) evaluating pumitamig (also known as BNT327 or BMS986545), an investigational bispecific antibody targeting PD-L1 x VEGF-A, plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). The data, which are consistent with data presented at European Lung Cancer Congress (ELCC) 2025 from a phase 2 trial conducted in China (NCT05844150), showed encouraging anti-tumour responses with a positive trend in the secondary endpoint progression free survival. Pumitamig plus chemotherapy demonstrated a manageable safety profile with no new safety signals and a low discontinuation rate. The data are presented as a late-breaker oral presentation at the IASLC 2025 World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer in Barcelona.
“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. 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,” 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-tumour responses relative to current standard of care.”
The interim analysis included 43 patients with untreated extensive-stage small cell lung cancer (Cohort 1) who received pumitamig in combination with standard of care chemotherapy in two dose levels. At the August 7, 2025 data cut-off, among 38 efficacy-evaluable patients, the confirmed overall response rate was 76.3% (85.0% at 20 mg/kg [dose level 1] and 66.7% at 30 mg/kg [dose level 2]) and the disease control rate (DCR) was 100%. The mean best percentage change in tumour size showed a tumour shrinkage of 56.7% with 89.5% of patients achieving early tumour 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%. Out of 43 patients, pumitamig-related treatment-emergent adverse events of Grade =3 were reported in 1 patient at dose level 1 and five patients at dose level 2.
“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 Prof. Özlem Türeci, M.D., co-founder and chief medical officer at BioNTech. “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 tumours. These interim data for pumitamig represent an important step in the right direction.”
“Today’s data add to the growing body of evidence indicating the potential of pumitamig to improve outcomes across a wide range of solid tumours,” said Bryan Campbell, senior vice president, head of program leadership, haematology, oncology, cell therapy at Bristol Myers Squibb. “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. 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.”
A global randomized phase 3 trial, ROSETTA-LUNG-01 (NCT06712355), evaluating pumitamig plus chemotherapy versus atezolizumab plus chemotherapy as a first-line treatment in patients with untreated ES-SCLC is ongoing. 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 to open globally. Pumitamig received Orphan Drug designation from the U.S. Food and Drug Administration (FDA) for the treatment of patients with small cell lung cancer in 2025.
The global randomized, open-label, parallel group Phase 2 clinical trial (BNT327-01; NCT06449209) evaluated pumitamig (BNT327/BMS986545) in patients with untreated extended-stage small-cell lung cancer (ES-SCLC) (Cohort 1) or small-cell lung cancer (SCLC) who progressed on first- or second-line treatment (Cohort 2 and Cohort 3). In Cohort 1, patients received pumitamig in two dose levels + chemotherapy (etoposide+carboplatin) for four 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. Cohort 2 and Cohort 3 explored the combination of two dose levels of pumitamig plus paclitaxel, or topotecan in the second- or third-line setting. The co-primary endpoints of the trial were per RECIST 1.1 objective response rate (ORR), change in tumour size and early tumour shrinkage, and safety per NCI CTCAE v5.0. Secondary endpoints include duration of response (DoR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS).
Small cell lung cancer (SCLC) accounts for 15% of all lung cancer cases, with an estimated 250,000 new cases globally per year. It is the most aggressive type of lung cancer often spreading early to other parts of the body and developing resistance mechanisms which makes it more challenging to treat. Platinum-based chemotherapy combined with etoposide chemotherapy has been the standard first-line treatment for decades. While the addition of immune checkpoint inhibitors to chemotherapy has shown improved survival outcomes for patients with advanced or extensive-stage disease, most patients progress within months after treatment, and the prognosis remains poor. The 5-year survival rate for patients with extensive-stage SCLC is only 5%, emphasizing the need for new treatment options that extend progression-free survival.
Pumitamig is a novel investigational bispecific antibody, jointly developed by BioNTech and BMS, combining two complementary, validated mechanisms in oncology into one single molecule. Pumitamig combines PD-L1 checkpoint inhibition aimed at restoring T cells’ ability to recognize and destroy tumour cells with the neutralization of VEGF-A. The blocking of VEGF-A is aimed at reversing the tumour’s immuno-suppressive effect in its microenvironment and cutting off the blood and oxygen supply that feeds tumour cells (anti-angiogenesis effect), with the intention of preventing the tumour from growing and proliferating. Pumitamig may be differentiated via its mechanism of action of targeting PD-L1 on tumour cells to localize anti-VEGF activity within the tumour microenvironment, aiming to enhance therapeutic precision and minimize systemic exposure.
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 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, 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 (ROSETTA LUNG-01; NCT06712355), first-line non-small cell lung cancer (ROSETTA LUNG-02; NCT06712316) and first-line triple-negative breast cancer (ROSETTA BREAST-01). Additional trials are ongoing exploring novel treatment combinations of pumitamig, including combinations with BioNTech’s proprietary antibody-drug conjugate candidates (ADCs) or immunomodulator candidates.
Biopharmaceutical New Technologies (BioNTech) is a global next generation immunotherapy company pioneering novel investigative therapies for cancer and other serious diseases. BioNTech exploits a wide array of computational discovery and therapeutic modalities with the intent of rapid development of novel biopharmaceuticals.
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases.
|