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

NCT ID: NCT06892548

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

594 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-05-02

Study Completion Date

2031-06-30

Brief Summary

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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

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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

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Advanced Lung Cancer

Keywords

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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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part 1 - BNT324 + BNT327 combination therapy

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

Group Type EXPERIMENTAL

BNT324

Intervention Type BIOLOGICAL

Intravenous infusion

BNT327

Intervention Type BIOLOGICAL

Intravenous infusion

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)

Group Type EXPERIMENTAL

BNT324

Intervention Type BIOLOGICAL

Intravenous infusion

BNT327

Intervention Type BIOLOGICAL

Intravenous infusion

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

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

Group Type EXPERIMENTAL

BNT324

Intervention Type BIOLOGICAL

Intravenous infusion

BNT327

Intervention Type BIOLOGICAL

Intravenous infusion

Part 2 - Cohort 3: RP2D of BNT324 + BNT327

In subpopulation 1 of NSCLC AGA negative, 2L+

Group Type EXPERIMENTAL

BNT324

Intervention Type BIOLOGICAL

Intravenous infusion

BNT327

Intervention Type BIOLOGICAL

Intravenous infusion

Part 2 - Cohort 4: RP2D of BNT324 + BNT327

In subpopulation 2 of NSCLC AGA negative, 1L

Group Type EXPERIMENTAL

BNT324

Intervention Type BIOLOGICAL

Intravenous infusion

BNT327

Intervention Type BIOLOGICAL

Intravenous infusion

Part 2 - Cohort 5: RP2D of BNT324 + BNT327

In subpopulation 2 of NSCLC AGA negative, 2L+

Group Type EXPERIMENTAL

BNT324

Intervention Type BIOLOGICAL

Intravenous infusion

BNT327

Intervention Type BIOLOGICAL

Intravenous infusion

Part 2 - Cohort 6: RP2D of BNT324 + BNT327

In NSCLC AGA positive

Group Type EXPERIMENTAL

BNT324

Intervention Type BIOLOGICAL

Intravenous infusion

BNT327

Intervention Type BIOLOGICAL

Intravenous infusion

Part 2 - Cohort 7: RP2D of BNT324 + BNT327

In SCLC, 1L

Group Type EXPERIMENTAL

BNT324

Intervention Type BIOLOGICAL

Intravenous infusion

BNT327

Intervention Type BIOLOGICAL

Intravenous infusion

Interventions

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BNT324

Intravenous infusion

Intervention Type BIOLOGICAL

BNT327

Intravenous infusion

Intervention Type BIOLOGICAL

Other Intervention Names

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DB-1311

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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DualityBio Inc.

INDUSTRY

Sponsor Role collaborator

Biotheus Inc.

INDUSTRY

Sponsor Role collaborator

BioNTech SE

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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BioNTech Responsible Person

Role: STUDY_DIRECTOR

BioNTech SE

Locations

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Precision NextGen Oncology and Research Center

Beverly Hills, California, United States

Site Status RECRUITING

Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status RECRUITING

John Theurer Cancer Center at Hackensack UMC

Hackensack, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center (MSKCC)

New York, New York, United States

Site Status RECRUITING

Icahn School of Medicine at Mount Sinai PRIME

New York, New York, United States

Site Status RECRUITING

Texas Oncology - Northeast

Tyler, Texas, United States

Site Status RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, United States

Site Status RECRUITING

Sunshine Hospital

Saint Albans, Victoria, Australia

Site Status RECRUITING

Guangxi Medical University Cancer Hospital

Nanning, Guangxi Zhuang, China

Site Status RECRUITING

Xiangyang Central Hospital

Xiangyang, Hubei, China

Site Status RECRUITING

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Site Status RECRUITING

Linyi Cancer Hospital

Shandong, Linyi, China

Site Status RECRUITING

Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine

Hangzhou, Zhejiang, China

Site Status RECRUITING

Adana City Hospital

Adana, , Turkey (Türkiye)

Site Status RECRUITING

Hacettepe University Medical Faculty

Ankara, , Turkey (Türkiye)

Site Status RECRUITING

Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital

Ankara, , Turkey (Türkiye)

Site Status RECRUITING

Yeditepe University Medical School Hospital

Istanbul, , Turkey (Türkiye)

Site Status RECRUITING

Bristol Haematology and Oncology Centre

Bristol, , United Kingdom

Site Status RECRUITING

St. James's University Hospital

Leeds, , United Kingdom

Site Status RECRUITING

University College London Hospital

London, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia China Turkey (Türkiye) United Kingdom

Central Contacts

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BioNTech clinical trials patient information

Role: CONTACT

Phone: +49 6131 9084

Email: [email protected]

Other Identifiers

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2024-520238-31-00

Identifier Type: CTIS

Identifier Source: secondary_id

BNT324-01

Identifier Type: -

Identifier Source: org_study_id