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
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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).
To evaluate the efficacy, safety, and dose optimization of BNT323/DB-1303 in combination with BNT327 in pts with hormone receptor (HR)-positive or -negative, HER2-expressing or HER2-null BC
The trial consists of two parts: Part 1 - Dose escalation in advanced HR+, HER2-low BC pts with prior chemotherapy to determine the recommended phase 2 dose (RP2D).
Part 2 - Dose optimization (cohort 1) and exploratory cohorts (cohorts 2-3) will enroll HR+ or HR-, HER2-positive, HER2-low, HER2-ultralow, HER2-null, or triple-negative BC pts
- 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.
- 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-, 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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