NCT06892548

A Clinical Study to Investigate the Efficacy and Safety of an Investigational Combination Therapy With BNT324 and BNT327 in Patients With Advanced Lung Cancer

A Phase Ib/II, Multi-site, Open-label, Two-part Trial to Evaluate the Efficacy, Safety, Pharmacokinetics, and Recommended Combination Dose of BNT324 With BNT327 in Participants With Advanced Lung Cancer

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 594 (estimated)
• Sponsor: BioNTech SE · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study aims to investigate the combination of BNT324, a B7-H3 antibody-drug conjugate (ADC) with BNT327, a programmed death-ligand 1 (PD-L1) and vascular endothelial growth factor (VEGF) bispecific antibody, in participants with advanced/metastatic or relapsed/progressive small cell lung cancer (SCLC) and non small cell lung cancer (NSCLC).

Detailed description

This is a two-part study designed to evaluate and establish two safe combination dose levels (recommended Phase 2 dose \[RP2D\] and a lower/another combination dose level \[RP2D-1\]) of BNT324 with BNT327 (Part 1), to determine the optimal combination dose (dose optimization \[DO\]) in NSCLC and SCLC lead indication cohorts at the RP2D and RP2D-1, to evaluate the preliminary efficacy in selected lung cancer cohorts at the highest combination dose level (in a signal seeking Part 2), and to confirm the clinical efficacy of BNT324 in combination with BNT327 at the optimal dose level in participants with advanced lung cancer in expansion cohorts (proof-of-concept \[POC\] cohorts). The study consists of a screening period, a treatment period, a safety follow-up period, and a long-term survival follow-up period. In Part 1 participants with histologically or cytologically confirmed relapsed or progressive lung cancer (both SCLC and NSCLC are eligible) will receive BNT324 in combination with BNT327 using a dose escalation design. In Part 2 of the study, BNT324 will be studied in combination with BNT327 at the RP2D compared to RP2D-1 in participants with advanced metastatic treatment-naïve NSCLC (DO Cohort 1) and relapsed/progressive SCLC after failure of cytotoxic chemotherapy with or without immuno-oncology (IO) (DO Cohort 2). The totality of the available data (e.g., safety, efficacy, pharmacokinetics etc.) will be reviewed to select the optimal dose. After the optimal dose is selected, additional participants in each cohort may be enrolled in the selected optimal dose. In the signal seeking cohorts (Cohort 3-7), participants will receive BNT324 in combination with BNT327 at the RP2D from Part 1. A predefined number of participants in Part 2 Cohort 1 and Cohort 2 will be randomized to one of the two dose levels (RP2D and RP2D-1) selected from Part 1 in a 1:1 ratio. Additional participants in Part 2 Cohort 1 and Cohort 2 may be enrolled in the selected optimal dose to further assess the efficacy and safety profile. No randomization is planned for any other cohort in Part 2 or Part 1.

Conditions

• Advanced Lung Cancer

Interventions

Type	Name	Description
BIOLOGICAL	BNT324	Intravenous infusion
BIOLOGICAL	BNT327	Intravenous infusion

Timeline

• Start date: 2025-05-02
• Primary completion: 2027-08-01
• Completion: 2031-06-01
• First posted: 2025-03-24
• Last updated: 2026-04-15

Locations

58 sites across 6 countries: United States, Australia, China, Taiwan, Turkey (Türkiye), United Kingdom

Regulatory

• FDA-regulated drug study