Recruiting
Phase 1
Phase 2

BNT324 & BNT327

Sponsor:

BioNTech SE

Code:

NCT06892548

Conditions

Advanced Lung Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

BNT324

BNT327

Study Details

Brief 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).

Conditions

Advanced Lung Cancer

Study ID

NCT06892548

Start date

May 2, 2025

Status verified date

Aug, 2026

Completion date

May, 2032

Anticipated

Primary completion date

Sep, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

594 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part 1 - BNT324 + BNT327 combination therapy

Escalating combination dose levels of BNT324 and BNT327 to define RP2D and RP2D-1 for NSCLC and SCLC.

experimental: Part 2 - Cohort 1: RP2D of BNT324 + BNT327 and RP2D-1 of BNT324 + BNT327

In subpopulation 1 of NSCLC actionable oncogenic alteration (AGA) negative, first-line (1L)

experimental: Part 2 - Cohort 2: RP2D of BNT324 + BNT327 and RP2D-1 of BNT324 + BNT327

In SCLC, second-line plus (2L+)

experimental: Part 2 - Cohort 3: RP2D of BNT324 + BNT327

In subpopulation 1 of NSCLC AGA negative, 2L+

experimental: Part 2 - Cohort 4: RP2D of BNT324 + BNT327

In subpopulation 2 of NSCLC AGA negative, 1L

experimental: Part 2 - Cohort 5: RP2D of BNT324 + BNT327

In subpopulation 2 of NSCLC AGA negative, 2L+

experimental: Part 2 - Cohort 6: RP2D of BNT324 + BNT327

In NSCLC AGA positive

experimental: Part 2 - Cohort 7: RP2D of BNT324 + BNT327

In SCLC, 1L

Interventions

BNT324

Intravenous infusion

BNT327

Intravenous infusion

Primary outcome measure

  • Part 1 - Occurrence of dose limiting toxicities (DLTs) by dose level [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 87 months ]
  • Part 2 cohorts 3-7 - ORR by cohort [ Time Frame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 87 months ]

Central Contacts and Locations

Central contacts

BioNTech clinical trials patient information

+49 6131 9084patients@biontech.de

Locations

Mayo Clinic Arizona

Recruiting

Phoenix, Arizona, United States, 13400

Precision NextGen Oncology and Research Center

Recruiting

Beverly Hills, California, United States, 90212

Cedars Sinai Medical Center

Recruiting

Los Angeles, California, United States, 90048

UCLA - David Geffen School of Medicine

Recruiting

Santa Monica, California, United States, 90404

University of Colorado Cancer Center

Recruiting

Aurora, Colorado, United States, 80045

Mayo Clinic in Florida

Recruiting

Jacksonville, Florida, United States, 32224

University of Iowa Hospitals & Clinics PARENT

Recruiting

Iowa City, Iowa, United States, 52242

Mayo Clinic-Rochester

Recruiting

Rochester, Minnesota, United States, 55905

Regional Cancer Care Associates

Recruiting

Belleville, New Jersey, United States, 07109

John Theurer Cancer Center at Hackensack UMC

Recruiting

Hackensack, New Jersey, United States, 07601

Memorial Sloan Kettering Cancer Center (MSKCC)

Recruiting

New York, New York, United States, 10021

Icahn School of Medicine at Mount Sinai PRIME

Recruiting

New York, New York, United States, 10029

Cleveland Clinic Taussig Cancer Institute Case Comprehensive Cancer Center

Recruiting

Cleveland, Ohio, United States, 44195

Texas Oncology - DFW

Recruiting

Dallas, Texas, United States, 75246

MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Texas Oncology - Northeast

Recruiting

Tyler, Texas, United States, 75702

Virginia Cancer Specialists

Recruiting

Fairfax, Virginia, United States, 22031

More Information

Sponsor

BioNTech SE

Last update posted

Aug 26, 2026

Last verified

Aug, 2026

Keywords

  • Small cell lung cancer (SCLC)
  • Non-small cell lung cancer (NSCLC)
  • Programmed death-ligand 1 (PD-L1)
  • Vascular endothelial growth factor (VEGF)
  • Bispecific antibody
  • BNT324 (DB-1311)
  • BNT327
  • Combination with chemotherapy
  • Combination with other investigational agents
  • Immunotherapy
  • Treatment-naïve

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by BioNTech SE on 2026-08-26.