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

Last updated: August 11, 2025
Sponsor: BioNTech SE
Overall Status: Active - Recruiting

Phase

1/2

Condition

N/A

Treatment

BNT327

BNT324

Clinical Study ID

NCT06892548
BNT324-01
2024-520238-31-00
  • Ages > 18
  • All Genders

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 Criteria

Inclusion

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 metastaticdisease. Participants with mixed histology must be classified based on the maincomponent. Participants with NSCLC are eligible with any or no PD-L1 expression.Participants with AGA-positive disease must have received targeted therapy prior toenrollment 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

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 thefirst-line/treatment-naïve cohorts in the advanced/metastatic setting. Priortreatment with ADC with topoisomerase inhibitor payload is only allowed forparticipants in the second-line plus cohorts in the advanced/metastatic setting.

  • Is a candidate to locoregional treatment (including surgical resection, stereotacticradiotherapy or tumor ablation) with potential to induce complete or near completeresponse and prolonged tumor control (sometimes described as "radical" intent), perinvestigator's assessment.

  • Has a history of significant hematologic toxicity to prior lines of therapy, asassessed by investigator, e.g., Grade 4 febrile neutropenia or recurrent/persistentGrade 3 to 4 neutropenia.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply to all or some participants depending on the cohort.

Study Design

Total Participants: 594
Treatment Group(s): 2
Primary Treatment: BNT327
Phase: 1/2
Study Start date:
May 02, 2025
Estimated Completion Date:
June 30, 2031

Study 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.

Connect with a study center

  • Hacettepe University Medical Faculty

    Ankara, 06100
    Turkey

    Active - Recruiting

  • Bristol Haematology and Oncology Centre

    Bristol, BS2 8ED
    United Kingdom

    Active - Recruiting

  • University College London Hospital

    London, W1T 7HA
    United Kingdom

    Active - Recruiting

  • Precision NextGen Oncology and Research Center

    Beverly Hills, California 90212
    United States

    Active - Recruiting

  • John Theurer Cancer Center at Hackensack UMC

    Hackensack, New Jersey 07601
    United States

    Active - Recruiting

  • Virginia Cancer Specialists

    Fairfax, Virginia 22031
    United States

    Active - Recruiting

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