BNT327 With Chemotherapy Elicits Strong Results in ES-SCLC

Small tumor cancer cells: © Yuriy - stock.adobe.com

The PD-L1 and VEGF-A bispecific antibody BNT327 demonstrated encouraging clinical activity and had a tolerable safety profile when combined with chemotherapy as a first-line treatment in extensive-stage small cell lung cancer (ES-SCLC), according to a phase 2 trial (NCT05844150) presented at the 2025 European Lung Cancer Congress (ELCC).¹

As of the cutoff date of December 20, 2024, 48 patients had completed at least 1 tumor evaluation, and 5 patients remained on treatment. The median treatment exposure was 5.7 months (95% CI, 4.4-7.2). At a median follow-up of 14.5 months (95% CI, 13.4-15.3), the confirmed overall response rate (ORR) was 85.4% (95% CI, 72.2%-93.9%) and the unconfirmed ORR was 87.5% (95% CI, 74.8%-95.3%).

The disease control rate (DCR) was 97.9% (95% CI, 88.9%-100%). The 6-month and 12-month OS rates were 91.7% (95% CI, 79.3%-96.8%) and 72.7% (95% CI, 57.6%-83.1%), respectively. The median OS was not yet mature.

“BNT327 combined with platinum-based chemotherapy as a [first-line] treatment for ES-SCLC demonstrated encouraging efficacy,” wrote investigators in the poster. “BNT327 in combination with platinum-based chemotherapy exhibited an acceptable tolerability profile, with a low discontinuation rate and no treatment-related deaths reported.”

For safety, at a data cutoff date of December 20, 2024, all patients had at least 1 adverse event (AE) related to treatment with BNT327 and/or chemotherapy, and 43 patients (86%) experienced grade 3 or higher treatment-related AEs (TRAEs). Neutrophil count decrease (90%), anemia (80%), white blood cell count decrease (76%), and platelet count decrease (62%) were the most common TRAEs.

All TRAEs of special interest were grade 1 to 3, including hypertension (26%), proteinuria (16%), and various forms of hemorrhage (6%). Immune-related AEs were seen in 42% of patients, with grade 3 or higher in 10%. Further, 3 patients (6%) discontinued treatment due to TRAEs and there were no treatment-related deaths reported in the study.

About BNT327 and the Phase 2 Trial

BNT327 is an investigational bispecific antibody that targets PD-L1 and VEGF-A in the tumor and tumor microenvironment. The dual targeting of PD-L1 and VEGF-A combines 2 complementary modalities, which works to improve efficacy and safety.¹

In the open-label, single-arm, multisite phase 2 trial of BNT327, patients aged 18 years and older with histologically or cytologically confirmed ES-SCLC were enrolled.² Patients must have received no prior systemic therapy for ES-SCLC, are required to have a life expectancy of at least 12 weeks, an ECOG performance status of 0 or 1, and adequate organ function.

The study completed enrollment on November 21, 2023, with 50 patients enrolled in the trial.¹ The median age of patients was 59 years (range, 46-75), most patients were male (68%), had an ECOG performance status of 1 (80%), and 3 or more metastatic sites (54%). Five patients (10%) had metastases of the brain and 15 (30%) had metastases of the liver. Further, 33 patients (66%) were smokers.

Patients were treated with BNT327 at a dose of 30 mg/kg via intravenous (IV) infusion plus IV etoposide 100 mg/m² on days 1 to 3, and IV platinum once every 3 weeks for 4 cycles.

The primary end point was ORR and secondary end points were OS, PFS, DCR, duration of response, time to response per RESIST v1.1, and safety,

References

1. Cheng Y, Shi J, Meng X, et al. Phase 2 study of the efficacy and safety of BNT327/PM8002 plus systemic chemotherapy as first-line therapy for extensive-stage small-cell lung cancer (ES-SCLC). Presented at: 2025 European Lung Cancer Congress; March 26-29, 2025; Paris, France. 302P.

2. A study of PM8002 (Anti-PD-L1/​VEGF) in combination with chemotherapy in patients with ES-SCLC. ClinicalTrials.gov. Updated March 25, 2025. Accessed March 28, 2025. https://clinicaltrials.gov/study/NCT05844150?tab=table