A Phase I/II, Multi-site, Open-label, Two-part Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of BNT323 in Combination With BNT327 in Participants With Advanced Breast Cancer

Study Identifier:
BNT323-03-START
CT.gov Identifier:
NCT06827236
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
2024-517979-20-00
Study Contact Information:
(210) 593-5651 or [email protected]
Will Be Recruiting

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Study 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).

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Breast
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    Phase 1 and 2
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: Part1 - BNT323 + BNT327 combination therapy
    • Read More
  • Drug: Experimental: Part 2 Cohort 1 - RP2D of BNT323 + BNT327
  • Drug: Experimental: Part 2 Cohort 1 - Lower dose or RP2D of BNT323 + BNT327
  • Drug: Experimental: Part 2 Cohort 1 - BNT323 monotherapy
  • Drug: Experimental: Part 2 Cohort 1 - BNT327 monotherapy
  • Drug: Experimental: Part 2 Cohort 2 - Selected dose level of BNT323 + BNT327
  • Drug: Experimental: Part 2 Cohort 3 - Selected dose level of BNT323 + BNT327
  • Drug: Unknown: Experimental: Part 2 Cohort 4 - Selected dose level of BNT323 + BNT327
  • Drug: Unknown: Drug: BNT327
  • Drug: Unknown: The study consists of two parts:
  • Drug: Unknown: Part 1 - Dose escalation: In Part 1 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.
  • Drug: Unknown:
  • Drug: Unknown: Chinese common name: BNT327
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Will Be Recruiting

    Requirements information
    Inclusion criteria
    • Inclusion Criteria:
    • Key Inclusion Criteria (applicable to all participants and all parts unless otherwise specified):
    • 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.
    • NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START San Antonio
    San Antonio, TX, United States, 78229
    Investigator
    Amita Patnaik
    Status
    Will Be Recruiting
    Condition(s) Treated at Site
    Breast