BioNTech's investigational bispecific antibody BNT327, when combined with standard chemotherapy, has demonstrated remarkable efficacy as a first-line treatment for extensive-stage small cell lung cancer (ES-SCLC), according to data presented at the 2025 European Lung Cancer Congress (ELCC).
In the open-label, single-arm Phase 2 trial, 85.4% of patients achieved a confirmed objective response rate (ORR), with disease control observed in nearly all participants (97.9%). These results suggest a potentially significant advancement in the treatment landscape for this aggressive form of lung cancer.
Strong Clinical Outcomes in Phase 2 Trial
The trial enrolled 50 patients with ES-SCLC who had not received prior systemic therapy. As of the December 20, 2024 data cutoff, 48 patients had completed at least one tumor evaluation, with five patients remaining on treatment. The median treatment exposure was 5.7 months.
At a median follow-up of 14.5 months, the confirmed ORR was 85.4% (95% CI, 72.2%-93.9%), with an unconfirmed ORR of 87.5% (95% CI, 74.8%-95.3%). The disease control rate reached an impressive 97.9% (95% CI, 88.9%-100%).
Survival data showed promising trends, with 6-month and 12-month overall survival (OS) rates of 91.7% and 72.7%, respectively. The median OS had not yet matured at the time of analysis. The median progression-free survival was reported at 6.9 months.
"BNT327 combined with platinum-based chemotherapy as a first-line treatment for ES-SCLC demonstrated encouraging efficacy," noted the investigators in their presentation.
Dual-Targeting Mechanism of Action
BNT327 represents an innovative approach to cancer treatment through its dual-targeting mechanism. The bispecific antibody simultaneously targets PD-L1 and VEGF-A in the tumor and tumor microenvironment.
By targeting PD-L1, the therapy enhances the immune system's ability to recognize and attack cancer cells. Simultaneously, its action on VEGF-A inhibits angiogenesis—the formation of new blood vessels—effectively cutting off the tumor's nutrient supply. This complementary approach aims to improve both efficacy and safety compared to single-target therapies.
BioNTech acquired full ownership of BNT327 in November 2024 through an $800 million upfront acquisition of its partner Biotheus, highlighting the company's confidence in the therapy's potential.
Treatment Protocol and Patient Demographics
In the trial, patients received BNT327 at a dose of 30 mg/kg via intravenous infusion, combined with IV etoposide (100 mg/m² on days 1-3) and IV platinum once every three weeks for four cycles. Following this initial treatment, patients continued on BNT327 maintenance therapy until disease progression or unacceptable toxicity occurred.
The study population had a median age of 59 years (range 46-75), with a predominance of male patients (68%). Most participants had an ECOG performance status of 1 (80%) and multiple metastatic sites, with 54% having three or more sites of metastasis. Brain metastases were present in 10% of patients, while 30% had liver metastases. Two-thirds (66%) of the patients were smokers.
Safety and Tolerability Profile
All patients experienced at least one adverse event related to the treatment regimen. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 86% of patients, with hematological toxicities being most common: neutrophil count decrease (90%), anemia (80%), white blood cell count decrease (76%), and platelet count decrease (62%).
Adverse events of special interest included hypertension (26%), proteinuria (16%), and various forms of hemorrhage (6%), though all were grade 1-3 in severity. Immune-related adverse events occurred in 42% of patients, with 10% experiencing grade 3 or higher events.
Despite these adverse events, the discontinuation rate due to treatment-related toxicities was relatively low at 6% (three patients), and no treatment-related deaths were reported. Two deaths occurred during the study but were not attributed to the treatment.
"BNT327 in combination with platinum-based chemotherapy exhibited an acceptable tolerability profile, with a low discontinuation rate and no treatment-related deaths reported," the investigators concluded.
Context in the Treatment Landscape
Small cell lung cancer represents approximately 15% of all lung cancer cases and is characterized by aggressive growth and early metastasis. The extensive-stage form of the disease, where cancer has spread beyond the original site, has historically had poor outcomes with limited treatment options.
The current standard of care for ES-SCLC typically involves platinum-based chemotherapy combined with immunotherapy, but response durability remains a challenge. The high response rate and promising survival data from the BNT327 trial suggest this dual-targeting approach could potentially offer improved outcomes for patients with this difficult-to-treat malignancy.
These results follow earlier data presented by BioNTech in December 2024 from a Phase Ib/II study, which showed a 73.8% overall response rate at a median follow-up of 18.1 months, with a median duration of response of 11.7 months.
The emerging class of cancer therapies targeting both PD-1/PD-L1 and VEGF pathways has been gaining attention in the oncology community, particularly after Akeso and Summit Therapeutics reported that their PD-1/VEGF bispecific antibody ivonescimab outperformed Keytruda in a Phase III non-small cell lung cancer trial in September 2024.
As the trial continues and data mature, oncologists and patients will be watching closely to see if BNT327 can maintain these impressive response rates and translate them into meaningful survival benefits for patients with ES-SCLC.
