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

NCT06892548 · tracked via the Priya Life Science UK tracker

Sponsor

BioNTech SE

Phase

Phase 1/2

Started

2025-05-02

Last updated

2026-08-26

Condition(s) studied

Advanced Lung Cancer

Investigational drug(s) / intervention(s)

BNT324BNT327

BNT324: Intravenous infusion

BNT327: Intravenous infusion

Study 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).

Eligibility

Sex

ALL

Min age

18 Years

Max age

—

Healthy volunteers

Inclusion Criteria: * Aged ≥18 years at the time of giving informed consent. * Histological or cytological confirmed unresectable advanced/metastatic lung cancer. Histological classification may be based on tumor samples prior to metastatic disease. Participants with mixed histology must be classified based on the main component. Participants with NSCLC are eligible with any or no PD-L1 expression. Participants with AGA-positive disease must have received targeted therapy prior to enrollment in this study. * Part 1: Participants with NSCLC and SCLC * Part 2 Cohort 1: Participants with NSCLC (subpopulation 1) AGA negative, 1L * Part 2 Cohort 2: Participants with SCLC, 2L+ * Part 2 Cohort 3: Participants with NSCLC (subpopulation 1) AGA negative, 2L+ * Part 2 Cohort 4: Participants with NSCLC (subpopulation 2) AGA negative, 1L * Part 2 Cohort 5: Participants with NSCLC (subpopulation 2) AGA negative, 2L+ * Part 2 Cohort 6: Participants with NSCLC AGA positive * Part 2 Cohort 7: Participants with SCLC, 1L * Have measurable disease defined by RECIST version 1.1. * Have an Eastern Cooperative Oncology Group performance status of 0 or 1. * Have a life expectancy of ≥12 weeks. Exclusion Criteria: * Prior treatment with B7-H3 targeted therapy. * Prior treatment with ADC with topoisomerase inhibitor (e.g., datopotamab deruxtecan, trastuzumab deruxtecan). Note: This exclusion applies to participants in the first-line/treatment-naïve cohorts in the advanced/metastatic setting. Prior treatment with ADC with topoisomerase inhibitor payload is only allowed for participants in the second-line plus cohorts in the advanced/metastatic setting. * Is a candidate to locoregional treatment (including surgical resection, stereotactic radiotherapy or tumor ablation) with potential to induce complete or near complete response and prolonged tumor control (sometimes described as "radical" intent), per investigator's assessment. * Has a history of significant hematologic toxicity to prior lines of therapy, as assessed by investigator, e.g., Grade 4 febrile neutropenia or recurrent/persistent Grade 3 to 4 neutropenia. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply to all or some participants depending on the cohort.

Primary outcome measure(s)

Part 1 - Occurrence of dose limiting toxicities (DLTs) by dose level — During the DLT evaluation period, i.e., the time of initiation of the first dose of investigational medicinal product (IMP) up to 21 days]
Part 1 - Occurrence of Treatment-emergent adverse events (TEAEs), serious TEAEs, treatment-related TEAEs, and treatment-related serious TEAEs by dose level — From the time of the first dose of IMP to 90 days after the last IMP dose or until new anticancer therapy is started, whichever occurs first
Part 1 - Occurrence of dose interruption, reduction, and treatment discontinuations due to TEAEs by dose level — From the time of the first dose of IMP to 90 days after the last dose of IMP or until new anticancer therapy is started, whichever occurs first
Part 2 cohorts 1 and 2 - Occurrence of TEAEs, serious TEAEs, treatment-related TEAEs, and treatment-related serious TEAEs by cohort and treatment arm — From the time of the first dose of IMP to 90 days after the last IMP dose or until new anticancer therapy is started, whichever occurs first
Part 2 cohorts 1 and 2 - Occurrence of dose interruption, reduction, and treatment discontinuation due to TEAEs by cohort and treatment arm — From the time of the first dose of IMP to 90 days after the last IMP dose or until new anticancer therapy is started, whichever occurs first
Part 2 cohorts 1 and 2 - Objective response rate (ORR) by cohort and treatment arm — From the time of initiation of the first dose of IMP to end of study, i.e., up to 87 months
ORR defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) is observed as best overall response (per response evaluation criteria in solid tumors \[RECIST\] version 1.1 based on the investigator's assessment).
Part 2 cohorts 3-7 - ORR by cohort — From the time of initiation of the first dose of IMP to end of study, i.e., up to 87 months
ORR, defined as the proportion of participants in whom a confirmed CR or PR is observed as best overall response (per RECIST version 1.1 based on the investigator's assessment).

Trial sites (91)

Facility	City	Region	Status
Mayo Clinic Arizona	Phoenix	Arizona	Recruiting
Precision NextGen Oncology and Research Center	Beverly Hills	California	Recruiting
Cedars Sinai Medical Center	Los Angeles	California	Recruiting
UCLA - David Geffen School of Medicine	Santa Monica	California	Recruiting
University of Colorado Cancer Center	Aurora	Colorado	Recruiting
Mayo Clinic in Florida	Jacksonville	Florida	Recruiting
University of Iowa Hospitals & Clinics PARENT	Iowa City	Iowa	Recruiting
Mayo Clinic-Rochester	Rochester	Minnesota	Recruiting
Regional Cancer Care Associates	Belleville	New Jersey	Recruiting
John Theurer Cancer Center at Hackensack UMC	Hackensack	New Jersey	Recruiting
Memorial Sloan Kettering Cancer Center (MSKCC)	New York	New York	Recruiting
Icahn School of Medicine at Mount Sinai PRIME	New York	New York	Recruiting
Cleveland Clinic Taussig Cancer Institute Case Comprehensive Cancer Center	Cleveland	Ohio	Recruiting
Texas Oncology - DFW	Dallas	Texas	Recruiting
MD Anderson Cancer Center	Houston	Texas	Recruiting
Texas Oncology - Northeast	Tyler	Texas	Recruiting
Virginia Cancer Specialists	Fairfax	Virginia	Recruiting
Chris O'Brien Lifehouse	Camperdown	New South Wales	Recruiting
Flinders Medical Centre	Bedford Park	South Australia	Recruiting
Bendigo Hospital	Bendigo	Victoria	Recruiting
Barwon Health	Geelong	Victoria	Recruiting
Sunshine Hospital	Saint Albans	Victoria	Recruiting
St John of God Subiaco Hospital	Subiaco	Western Australia	Recruiting
Anhui Provincial Cancer Hospital	Hefei	Anhui	Recruiting
Beijing Cancer Hospital	Beijing	Beijing Municipality	Recruiting
Beijing GoBroad Hospital	Beijing	Beijing Municipality	Recruiting
Fujian Medical University Union Hospital	Fuzhou	Fujian	Recruiting
Fujian Cancer Hospital	Fuzhou	Fujian	Recruiting
Guangxi Medical University Cancer Hospital	Nanning	Guangxi Zhuang	Recruiting
The First Affiliated Hospital of Xinxiang Medical University	Weihui	Henan	Recruiting
Henan Provincial Cancer Hospital	Zhengzhou	Henan	Recruiting
Jingzhou First People's Hospital	Jingzhou	Hubei	Recruiting
Xiangyang Central Hospital	Xiangyang	Hubei	Recruiting
Yichang Central People's Hospital	Yichang	Hubei	Recruiting
Hunan Province People's Hospital	Changsha	Hunan	Recruiting
Nanjing Chest Hospital	Nanjing	Jiangsu	Recruiting
The Second Affiliated Hospital of Nanchang University	Nanchang	Jiangxi	Recruiting
Jiangxi Cancer Hospital	Nanchang	Jiangxi	Recruiting
The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi	Recruiting
Jilin Cancer Hospital	Changchun	Jilin	Recruiting

+ 51 more sites — see the full list on the official registry below.

More BioNTech SE trials in the UK

A Clinical Trial to Test if an Investigational Combination Therapy With BNT326 and BNT327 is Safe and Potentially Beneficial for People With Advanced Non-small Cell Lung Cancer (NSCLC) Recruiting

Safety, Preliminary Effectiveness of BNT327, an Investigational Therapy for Patients With Small-cell Lung Cancer in Combination With Chemotherapy Active, not recruiting

Safety and Preliminary Efficacy of Pumitamig (BNT327), an Investigational Therapy for Patients With Non-small Cell Lung Cancer in Combination With Chemotherapy as First-line or Second-line Treatment Recruiting

A Clinical Trial Investigating the Safety, Tolerability, and Therapeutic Effects of BNT113 in Combination With Pembrolizumab Versus Pembrolizumab Alone for Patients With a Form of Head and Neck Cancer Positive for Human Papilloma Virus 16 and Expressing the Protein PD-L1 Active, not recruiting

Safety, Efficacy, and Pharmacokinetics of BNT327 in Combination With Chemotherapy and Other Investigational Agents for Lung Cancer Recruiting

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT06892548 on ClinicalTrials.gov ↗ ← All trials in the UK