WCLC 2025: China-Origin BNT327 (PD-L1/VEGF-A) Delivers Breakthrough ES-SCLC Results

Update (Aug 27, 2025): Ivonescimab’s OS benefit (HARMONi-A) confirmed, reinforcing its NSCLC edge vs. BNT327.

At the 2025 World Lung Cancer Conference (WCLC), BioNTech published compelling global Phase 2 abstract data for BNT327 (pumitamig), a bispecific antibody targeting PD-L1 and VEGF-A, in first-line ES-SCLC. Originally developed by China-based Biotheus, BNT327 had shown promising efficacy and safety in domestic Chinese trials before BioNTech acquired full global rights in 2024. The WCLC abstract represents the first comprehensive global dataset, demonstrating how a China-origin bispecific is now positioned to compete on the world stage.

Key Data Highlights

• Efficacy: Among 38 evaluable patients, the unconfirmed objective response rate (uORR) was 86.8%, with 33 partial responses and 5 stable disease cases, yielding a 100% disease control rate. Notably, the 20 mg/kg dose achieved a 95.0% uORR versus 77.8% for 30 mg/kg. In patients with ≥2 tumor assessments and >90 days’ follow-up, the confirmed ORR was 81.8% overall (100% for 20 mg/kg, 60% for 30 mg/kg). Tumor volumes shrank by an average of 47.3%, with 89.5% of patients showing early shrinkage.
• Biomarker Insights: Circulating tumor DNA (ctDNA) was detectable in 93.8% of patients at baseline, with a median tumor fraction (TFx) of 57.0%. By cycle 3, day 1, all 18 evaluable patients had reduced ctDNA levels, with a median TFx change of -99.3% and 44.4% achieving clearance, indicating potent early anti-tumor activity.
• Safety: Treatment-related adverse events occurred in 81.4% of patients, with 53.5% experiencing grade ≥3 events. BNT327-related grade ≥3 AEs were lower at 20 mg/kg (1 patient) than 30 mg/kg (5 patients, including hypertension, thrombocytopenia, hemoptysis, proteinuria, and pulmonary embolism). Six patients (14%) discontinued therapy due to adverse events; no treatment-related deaths were reported.

Biotheus’ China-Origin Role and Strategic Partnerships

BNT327 was initially developed by Biotheus in China, where early Phase 2 trials established its clinical potential in ES-SCLC. Recognizing its global promise, BioNTech acquired full worldwide rights in 2024 for $800 million, following an initial $55 million upfront acquisition in 2023. Leveraging BioNTech’s immunotherapy expertise and manufacturing capacity, the program rapidly transitioned to global trials. In June 2025, Bristol Myers Squibb (BMS) entered an $11.1 billion partnership with BioNTech to co-develop and commercialize BNT327, further accelerating its international footprint.

Mechanism and Clinical Impact

BNT327’s bispecific design simultaneously targets PD-L1 to restore T-cell function and VEGF-A to normalize tumor vasculature, countering the immunosuppressive and angiogenic environment of ES-SCLC. The 95% uORR in the 20 mg/kg arm compares favorably with benchmarks such as Tecentriq (60% ORR in IMpower133) and Imfinzi (68% in CASPIAN), indicating potential to redefine first-line treatment. Its profound ctDNA reduction (-99.3%) is particularly notable in PD-L1-low (“cold”) tumors, suggesting meaningful anti-tumor activity even in traditionally resistant cases.

Future Directions

The WCLC 2025 results propel BNT327 into the global Phase 3 ROSETTA Lung-01 trial (NCT06712355) for first-line ES-SCLC. Additional programs include NSCLC studies (NCT06712316, NCT06841055), second-line SCLC (NCT06616532 in China, NCT05879068 globally), and a Phase 1/2 combination study with a B7H3 ADC (NCT06892548). If Phase 3 confirms these findings, regulatory submissions could occur by 2027, with projected peak sales of $2 billion by 2032. Long-term safety and efficacy will determine whether BNT327 can become a new global standard of care.

Competitive Landscape

• Ivonescimab (Akeso/Summit): Targets PD-1 and has demonstrated a 49% reduction in NSCLC progression risk in the HARMONi-2 trial. Recent data from the HARMONi-A trial confirm a statistically significant and clinically meaningful overall survival benefit, enhancing its competitive edge over BNT327's PD-L1/VEGF-A dual mechanism.
• Established Therapies: Keytruda, Tecentriq, and Imfinzi rely on single-target approaches and may underperform in PD-L1-low tumors; BNT327’s bispecific design offers a potential edge.
• Emerging Bispecifics and ADCs: While other dual-target antibodies are in development, BNT327’s robust global Phase 2 data, BMS partnership, and favorable safety profile position it strongly for first-line ES-SCLC.

Outlook

BNT327 exemplifies how a China-origin therapy can transition to the global stage with high-impact results. The WCLC 2025 data highlight its potential to change the first-line ES-SCLC treatment paradigm. Ongoing Phase 3 trials, combination studies, and international partnerships will be critical to confirm its clinical and commercial potential, making BNT327 a key asset to watch in immuno-oncology.

Source

1. Heymach, J. V., Cho, B. C., Sezer, A., Karacin, C., Lee, Y. J., Çil, T., … Şahin, U. (2025). Global Phase 2 randomized trial of BNT327 (pumitamig; PD-L1 × VEGF-A bsAb) + chemotherapy for 1L ES-SCLC: Dose optimization analysis. WCLC 2025 Abstract OA13.02.
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