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

Active:	Yes
Cancer Type:	Breast Cancer	NCT ID:	NCT06827236
Trial Phases:	Phase I Phase II	Protocol IDs:	BNT323-03 (primary) NCI-2025-07527 1011776 2024-517979-20-00
Eligibility:	18 Years and older, Male and Female	Study Type:	Treatment
Study Sponsor:	Biontech SE
NCI Full Details:	http://clinicaltrials.gov/show/NCT06827236

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).

Objectives

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.

Treatment Sites in Georgia

University Cancer and Blood Center, LLC - Athens Medical Oncology
3320 Old Jefferson Road
Building 800
Athens, GA 30607
www.universitycancer.com

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