A Clinical Study to Find the Optimal Dose of an Investigational Treatment Called BNT323 When Used in Combination With Another Investigational Treatment, BNT327, and to Test if That Combination Treatment is Safe and Beneficial for Patients With Advanced Breast Cancer

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

380 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-04-23

Study Completion Date

2029-05-31

Brief Summary

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This is a Phase I/II, multi-site, open-label, two-part study designed to evaluate the efficacy, safety, optimized dose and contribution of components of BNT323 in combination with BNT327 in participants with hormone receptor-positive (HR+) or hormone receptor-negative (HR-), Human epidermal growth factor receptor (HER)2-positive, HER2-low (immunohistochemistry \[IHC\] 1+ or IHC 2+/in situ hybridization -), HER2-ultralow (IHC 0, with membrane staining) or HER2-null breast cancer (BC), or triple-negative breast cancer (TNBC).

Detailed Description

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The study consists of two parts:

* Part 1 - Dose escalation: In this part of the study, participants with histologically confirmed, chemotherapy-pretreated advanced HR+, HER2-low or HER2-ultralow BC will receive BNT323 in combination with BNT327 (BNT323 + BNT327) in a dose escalation design. This will define the recommended Phase 2 dose (RP2D) for the BNT323 + BNT327 combination therapy.
* Part 2 - Dose optimization and exploratory cohorts: This part of the study will be an expansion phase, aiming to evaluate the efficacy and safety of the optimal dose combination and providing a more robust comparison against the other treatments. It will start once the enrollment in Part 1 is completed and the sponsor in conjunction with the Safety Review Committee has assessed available Part 1 efficacy and safety data. Part 2 of the study will have four cohorts, i.e., Cohorts 1 (dose optimization cohort), and Cohorts 2, 3, and 4 (exploratory cohorts). Recruitment to Cohorts 2, 3, and 4 will begin with RP2D from Part 1 and in parallel to randomization in Cohort 1.

Randomization is planned for Cohort 1 in Part 2, i.e., participants will be randomized in 2:2:1:1 ratio into one of the four arms (RP2D of BNT323 + BNT327, lower dose of RP2D of BNT323 + BNT327, BNT323 monotherapy, and BNT327 monotherapy). No randomization is planned for any other cohort in Part 2.

Conditions

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Locally Advanced Breast Cancer Unresectable Breast Carcinoma Metastatic Breast Cancer

Keywords

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Breast Cancer (BC) Human epidermal growth factor receptor 2 (HER2) IHC scores 0, 1+, 2+, and 3+ Antibody drug conjugate (ADC) Programmed Death-1 (PD-1) Programmed Death Ligand-1 (PD-L1) Programmed Death-1 monoclonal antibodies Anti vascular endothelial growth factor-A (anti-VEGF-A)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part1 - BNT323 + BNT327 combination therapy

Part 2 Cohort 1 - BNT323 monotherapy

BNT323 monotherapy at a fixed dose

Group Type EXPERIMENTAL

BNT323

Eligibility Criteria

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Inclusion Criteria

* Have pathologically documented BC that:

* Is locally advanced, unresectable or metastatic.
* Has a confirmed HER2 status as determined by the local laboratory (Part 1, Part 2 Cohorts 2 and 4) or the central laboratory (Part 2, Cohorts 1 and 3) from the most recently collected pre-randomization tumor sample.
* Has a documented history of HER2 expression consistent with the subgroup definitions (i.e., HER2-low, HER2-ultralow, HER2-null, HER2-positive, or TNBC) as per current American Society of Clinical Oncology/College of American Pathologists guidelines.
* Have measurable disease defined by RECIST v1.1.
* Has left ventricular ejection fraction ≥55% by either echocardiography or multi-gated acquisition (scanning) within 28 days before randomization/enrollment.

Exclusion Criteria

* Have history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.
* Have an uncontrolled intercurrent illness that would limit compliance with study requirement or substantially increase risk of incurring adverse events.
* Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization/enrollment.
* Have a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
* Had prior treatment with topoisomerase I inhibitors, including ADCs with topoisomerase I inhibitor payloads such as trastuzumab deruxtecan.
* Have received any of the following therapies or drugs prior to the initiation of the study:

* Participants who have previously been randomized to or received treatment in a previous study with BNT323, regardless of treatment assignment.
* Participants who received prior treatment with a PD-L1/VEGF bispecific antibody. Note: Prior treatment with PD-1/VEGF bispecific antibodies, PD-1/PD-L1 inhibitors or anti-VEGF therapies are permitted.
* Have received other systemic immunostimulatory agents or immunosuppressive therapies (such as interferon-α, interleukin-2, or methotrexate) within 4 weeks prior to the initiation of study treatment or are within five half-lives of the treatment drug (whichever is longer). Exception: excluding local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short term use (≤7 days) of corticosteroids for prophylaxis (e.g., prevention of contrast agent allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens).
* Have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 3 weeks prior to the initiation of study treatment.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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BioNTech Responsible Person

Role: STUDY_DIRECTOR

BioNTech SE

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BioNTech clinical trials patient information

Role: CONTACT

Phone: +49 6131 9084

Email: [email protected]

Other Identifiers

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2024-517979-20-00

Identifier Type: CTIS

Identifier Source: secondary_id

1011776

Identifier Type: OTHER

Identifier Source: secondary_id

BNT323-03

Identifier Type: -

Identifier Source: org_study_id

A Clinical Study to Find the Optimal Dose of an Investigational Treatment Called BNT323 When Used in Combination With Another Investigational Treatment, BNT327, and to Test if That Combination Treatment is Safe and Beneficial for Patients With Advanced Breast Cancer

Study Results

Basic Information

Brief Summary

Detailed Description

Conditions

Keywords

Study Design

Study Groups

Part1 - BNT323 + BNT327 combination therapy

BNT323

BNT327

Part 2 Cohort 1 - RP2D of BNT323 + BNT327

BNT323

BNT327

Part 2 Cohort 1 - Lower dose or RP2D of BNT323 + BNT327

BNT323

BNT327

Part 2 Cohort 1 - BNT323 monotherapy

BNT323

Part 2 Cohort 1 - BNT327 monotherapy

BNT327

Part 2 Cohort 2 - Selected dose level of BNT323 + BNT327

BNT323

BNT327

Part 2 Cohort 3 - Selected dose level of BNT323 + BNT327

BNT323

BNT327

Part 2 Cohort 4 - Selected dose level of BNT323 + BNT327

BNT323

BNT327

Interventions

BNT323

BNT327

Eligibility Criteria

Inclusion Criteria

Exclusion Criteria

Sponsors

DualityBio Inc.

Biotheus Inc.

BioNTech (Shanghai) Pharmaceuticals Co., Ltd.

BioNTech SE

Responsible Party

Principal Investigators

BioNTech Responsible Person

Locations

Hematology - Oncology Associates of the Treasure Coast

Winship Cancer Institute of Emory University

START Midwest, LLC

Summit Medical Group

Memorial Sloan Kettering Hospital

South Texas Accelerated Research Therapeutics (START), LLC

Sichuan Cancer Hospital

Huizhou First Hospital

Fudan University Shanghai Cancer

LLC Arensia Exploratory Medicine

Institute of Oncology Arensia Exploratory Medicine

Addenbrooke s Hospital

St James's University Hospital

Royal Free Hospital

Countries

Central Contacts

BioNTech clinical trials patient information

Other Identifiers

2024-517979-20-00

1011776

BNT323-03