Dual PD-L1 × VEGF-A Antibody Pumitamig Delivers Strong Phase 2 Results in ES-SCLC

On September 8, 2025, BioNTech SE and Bristol Myers Squibb (BMS) announced interim results from a global Phase 2 trial (NCT06449209) of their bispecific antibody pumitamig (BNT327/BMS986545), combined with chemotherapy in previously untreated patients with extensive-stage small cell lung cancer (ES-SCLC). The data, presented at the 2025 World Conference on Lung Cancer (WCLC) in Barcelona, demonstrate encouraging antitumor activity in a disease with limited treatment options.

Phase 2 Trial Results

The open-label, multicenter study evaluated pumitamig plus etoposide and carboplatin in 43 treatment-naïve ES-SCLC patients, with 38 evaluable for efficacy as of the August 7, 2025 cutoff.

• Objective Response Rate (ORR): 76.3% overall; 85.0% at 20 mg/kg, 66.7% at 30 mg/kg.
• Disease Control Rate (DCR): 100%, with all patients achieving at least stable disease.
• Progression-Free Survival (PFS): Median of 6.8 months (6.3 months at 20 mg/kg; 7.0 months at 30 mg/kg).
• Tumor Shrinkage: Mean reduction of 56.7%, with 89.5% of patients showing early shrinkage.
• Safety: Manageable; no new safety signals identified. Grade ≥3 adverse events related to pumitamig occurred in 1 patient at 20 mg/kg and 5 patients at 30 mg/kg. Discontinuation rate was 14%, primarily due to neutropenia and infusion reactions.

These results align with prior Phase 2 data from China (NCT05844150) presented at ELCC 2025, reinforcing 20 mg/kg as the recommended dose for further development.

Development Background

Pumitamig was initially developed by Biotheus in China, where early clinical studies showed promising efficacy in SCLC. BioNTech acquired global rights in November 2024 for $800 million, following a $55 million option deal in 2023, integrating the drug into its oncology portfolio.

In June 2025, BioNTech and BMS entered into a strategic co-development and co-commercialization agreement worth up to $11.1 billion, structured around milestones and a 50:50 global profit split. This collaboration accelerates pumitamig’s late-stage clinical development and expansion into broader solid tumor indications.

Mechanism of Action

Pumitamig is a bispecific antibody that targets both:

• PD-L1, releasing inhibition of T-cell mediated antitumor immunity.
• VEGF-A, blocking tumor angiogenesis and improving immune infiltration.

This dual mechanism addresses the immunosuppressive and pro-angiogenic microenvironment characteristic of SCLC. Supporting preclinical data from other PD-L1 × VEGF bispecifics (e.g., HB0025) demonstrated enhanced antitumor activity compared with single-agent therapies, validating this therapeutic approach.

Competitive Landscape

• Atezolizumab (IMpower133): ORR ~60%.
• Durvalumab (CASPIAN): ORR ~68%.
  Pumitamig’s 76.3% ORR compares favorably, suggesting potential for superior efficacy.

In the bispecific antibody class, ivonescimab (PD-1 × VEGF; Akeso/Summit) has shown efficacy in NSCLC (HARMONi trial), but Phase 3 ES-SCLC data are lacking. Pumitamig is currently the most advanced PD-L1 × VEGF program in this indication.

Next Steps

• ROSETTA-LUNG-01 (NCT06712355): A global Phase 3 trial comparing pumitamig + chemotherapy vs. atezolizumab + chemotherapy in first-line ES-SCLC.
• Additional studies:
  • NSCLC: NCT06712316, NCT06841055
  • Second-line SCLC: NCT05879068
  • Antibody-drug conjugate (ADC) combinations in solid tumors.

Regulatory submissions are anticipated as early as 2027, with peak sales projections of $2 billion by 2032, depending on Phase 3 success.

Conclusion

The interim Phase 2 results for pumitamig underscore its potential to significantly improve outcomes in ES-SCLC. With a dual PD-L1 × VEGF mechanism, strong tumor shrinkage, and a favorable safety profile, pumitamig—under the strategic BioNTech-BMS partnership—could redefine the standard of care in first-line ES-SCLC.

References

1. BioNTech SE. First Disclosure of Global Interim Phase 2 Data for BioNTech and Bristol Myers Squibb PD-L1×VEGF-A Bispecific Antibody Pumitamig (BNT327/BMS986545) in Patients with Extensive-Stage Small-Cell Lung Cancer Shows Encouraging Antitumor Activity. BioNTech Investor News, September 8, 2025.
2. Bristol Myers Squibb. First Disclosure of Global Interim Phase 2 Data for BioNTech and Bristol Myers Squibb PD-L1×VEGF-A Bispecific Antibody Pumitamig (BNT327/BMS986545) in ES-SCLC. Bristol Myers Squibb Newsroom, September 8, 2025.
3. Cui, X.; Jia, H.; Xin, H.; Zhang, L.; Chen, S.; Xia, S.; Li, X.; Xu, W.; Chen, X.; Feng, Y.; Wei, X.; Yu, H.; Wang, Y.; Zhan, Y.; Zhu, X.; Zhang, X. A Novel Bispecific Antibody Targeting PD-L1 and VEGF With Combined Anti-Tumor Activities. Front. Immunol. 2021, 12, 778978.
4. Wu, C.; Wu, X. A Novel Designed Anti–PD-L1/OX40 Bispecific Antibody Augments Both Peripheral and Tumor-Associated Immune Responses for Boosting Antitumor Immunity. Mol. Cancer Ther. 2025, 24 (3), 317–330.
5. ClinicalTrials.gov. NCT06449209: Pumitamig in Combination With Chemotherapy in Treatment-Naïve ES-SCLC.
6. ClinicalTrials.gov. NCT05844150: Phase 2 Study of Pumitamig in Extensive-Stage SCLC (China).
7. ClinicalTrials.gov. NCT06712355: ROSETTA-LUNG-01 – Phase 3 Trial of Pumitamig in ES-SCLC.
8. ClinicalTrials.gov. NCT06712316: Pumitamig in NSCLC.
9. ClinicalTrials.gov. NCT06841055: Pumitamig in Solid Tumors.
10. ClinicalTrials.gov. NCT05879068: Pumitamig in Relapsed SCLC.