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

NCT06827236 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: BNT323-032024-517979-20-001011776
• Study Type: interventional
• Target: 380
• Locations: 8 countries
• Sites: 39

Brief Summary

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).

Conditions

Locally Advanced Breast Cancer; Unresectable Breast Carcinoma; Metastatic Breast Cancer

Keywords

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)

Outcome Measures

Primary Outcomes (4)

• Part 1 - Occurrence of dose limiting toxicities (DLTs)

  By dose level.

  During the DLT evaluation period (Cycle 1), i.e., the time of initiation of the first dose of investigational medicinal product (IMP) up to 21 days

• Occurrence of Treatment-emergent adverse events (TEAEs), Grade ≥3 TEAEs, serious adverse events (SAEs), treatment-related TEAEs, treatment-related Grade ≥3 TEAEs, and treatment-related SAEs

  In Part 1 by dose level. In Part 2 by cohort and arm.

  From the time of initiation of the first dose of IMP to 90 days after the last IMP dose

• Occurrence of dose interruption, reduction, and discontinuation due to TEAEs

  In Part 1 by dose level. In Part 2 by cohort and arm.

  From the time of initiation of the first dose of IMP to 90 days after the last IMP dose

• Part 2 - Objective response rate (ORR)

  ORR defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\] based on the investigator's assessment) is observed as best overall response. By cohort and arm.

  From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.

Secondary Outcomes (5)

• Part 1 - ORR

  From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.

• Part 2 - Duration of response (DoR)

  From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.

• Part 2 - Disease control rate (DCR)

  From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.

• Part 2 - Time to response (TTR)

  From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.

• Part 2 Cohort 1 only - Progression free survival (PFS)

  From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.

Study Arms (8)

Part1 - BNT323 + BNT327 combination therapy

EXPERIMENTAL

Escalating dose levels (DLs) of BNT323 and BNT327 to define RP2D. Six DLs are planned, i.e., DL0-1, DL1-1, DL2-1, DL0-0, DL1-0, DL2-0, a combination of three different DLs for BNT323 (DL0, DL1, and DL2) and two DLs for BNT327 (DL0 and DL1).

Drug: BNT323; Drug: BNT327

Part 2 Cohort 1 - RP2D of BNT323 + BNT327

EXPERIMENTAL

Drug: BNT323; Drug: BNT327

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

EXPERIMENTAL

Drug: BNT323; Drug: BNT327

Part 2 Cohort 1 - BNT323 monotherapy

EXPERIMENTAL

BNT323 monotherapy at a fixed dose

Drug: BNT323

Part 2 Cohort 1 - BNT327 monotherapy

EXPERIMENTAL

BNT327 monotherapy at a fixed dose

Drug: BNT327

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

EXPERIMENTAL

Drug: BNT323; Drug: BNT327

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

EXPERIMENTAL

Drug: BNT323; Drug: BNT327

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

EXPERIMENTAL

Drug: BNT323; Drug: BNT327

Interventions

BNT323 DRUG

Intravenous infusion

Part 2 Cohort 1 - BNT323 monotherapy; Part 2 Cohort 1 - Lower dose or RP2D of BNT323 + BNT327; Part 2 Cohort 1 - RP2D of BNT323 + BNT327; Part 2 Cohort 2 - Selected dose level of BNT323 + BNT327; Part 2 Cohort 3 - Selected dose level of BNT323 + BNT327; Part 2 Cohort 4 - Selected dose level of BNT323 + BNT327; Part1 - BNT323 + BNT327 combination therapy

BNT327 DRUG

Intravenous infusion

Part 2 Cohort 1 - BNT327 monotherapy; Part 2 Cohort 1 - Lower dose or RP2D of BNT323 + BNT327; Part 2 Cohort 1 - RP2D of BNT323 + BNT327; Part 2 Cohort 2 - Selected dose level of BNT323 + BNT327; Part 2 Cohort 3 - Selected dose level of BNT323 + BNT327; Part 2 Cohort 4 - Selected dose level of BNT323 + BNT327; Part1 - BNT323 + BNT327 combination therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• BioNTech SE: lead
• Biotheus Inc.: collaborator
• BioNTech (Shanghai) Pharmaceuticals Co., Ltd.: collaborator
• DualityBio Inc.: collaborator

Study Sites (39)

Beverly Hills Cancer Center

Beverly Hills, California, 90211, United States

RECRUITING

Hematology - Oncology Associates of the Treasure Coast

Port Saint Lucie, Florida, 34952, United States

RECRUITING

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

START Midwest, LLC

Grand Rapids, Michigan, 49546, United States

RECRUITING

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, 64111, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Summit Medical Group

Florham Park, New Jersey, 07932, United States

RECRUITING

Memorial Sloan Kettering Hospital

New York, New York, 10065, United States

RECRUITING

South Texas Accelerated Research Therapeutics (START), LLC

San Antonio, Texas, 78229, United States

RECRUITING

Sunnybrook Health Sciences Centre

Toronto, M4N 3M5, Canada

RECRUITING

The First Affiliated Hospital of Bengbu Medical College

Bengbu, 233004, China

RECRUITING

Jilin Cancer Hospital

Changchun, 130000, China

RECRUITING

Sichuan Cancer Hospital

Chengdu, 610041, China

RECRUITING

Sichuan Provincial People's Hospital

Chengdu, 610072, China

RECRUITING

The First Affiliated Hospital of Chongqing Medical University

Chongqing, 400016, China

RECRUITING

Huizhou First Hospital

Huizhou, 516003, China

RECRUITING

Guangxi Medical University Affiliated Tumor Hospital

Nanning, 530021, China

RECRUITING

Fudan University Shanghai Cancer

Shanghai, 201315, China

RECRUITING

The Second Affiliated Hospital of Xi an Jiaotong University

Xi'an, 710004, China

RECRUITING

Clinique Victor Hugo - Centre Jean Bernard

Le Mans, 72000, France

RECRUITING

Institut Claudius Regaud

Toulouse, 31059, France

RECRUITING

LLC Arensia Exploratory Medicine

Tbilisi, 0112, Georgia

RECRUITING

Institute of Oncology Arensia Exploratory Medicine

Chisinau, 2025, Moldova

RECRUITING

Medical Park Seyhan Hospital

Adana, 01140, Turkey (Türkiye)

RECRUITING

Adana City Hospital

Adana, 01230, Turkey (Türkiye)

RECRUITING

Hacettepe University Medical Faculty

Ankara, 06100, Turkey (Türkiye)

RECRUITING

Dr Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital

Ankara, 06200, Turkey (Türkiye)

RECRUITING

Ankara City Hospital

Ankara, 06800, Turkey (Türkiye)

RECRUITING

Yeditepe Universitesi Kosuyolu Hastanesi

Istanbul, 31755, Turkey (Türkiye)

RECRUITING

Koc University Hospital

Istanbul, 34010, Turkey (Türkiye)

RECRUITING

IAU Medical Park Florya Hospital

Istanbul, 34295, Turkey (Türkiye)

RECRUITING

Konya Necmettin Erbakan University Meram Medical Faculty

Konya, 42080, Turkey (Türkiye)

RECRUITING

Mersin City Education and Research Hospital

Mersin, 33240, Turkey (Türkiye)

RECRUITING

Addenbrooke s Hospital

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

Velindre Cancer Centre

Cardiff, CF14 2TL, United Kingdom

RECRUITING

St James's University Hospital

Leeds, LS9 7TF, United Kingdom

RECRUITING

Royal Free Hospital

London, NW3 2QG, United Kingdom

RECRUITING

The Christie Hospital

Manchester, M20 4BX, United Kingdom

RECRUITING

Royal Marsden Hospital-Sutton

Sutton, SM2 5PT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Central Study Contacts

BioNTech clinical trials patient information

CONTACT

+49 6131 9084; patients@biontech.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2025
• First Posted: February 14, 2025
• Study Start: April 23, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (9); MO (1); GB (6); TU (10); CN (9); CA (1); FR (2); GE (1)