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Finding the best dose of BNT323 and BNT327 for advanced breast cancer

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

Phase1; Phase2 Interventional BioNTech SE · NCT06827236

This study is testing the best dose of a new combination treatment for advanced breast cancer to see how well it works and if it's safe for patients.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment380 (estimated)
Ages18 Years and up
SexAll
SponsorBioNTech SE Industry-sponsored
Drugs / interventionstrastuzumab, methotrexate, prednisone, chemotherapy
Locations39 sites (Beverly Hills, California and 38 other locations)
Trial IDNCT06827236 on ClinicalTrials.gov

What this trial studies

This clinical study is designed to evaluate the safety and efficacy of a combination treatment involving BNT323 and BNT327 for patients with advanced breast cancer. It consists of two parts: the first part focuses on dose escalation to determine the optimal dose of the combination therapy, while the second part aims to assess the efficacy and safety of this optimal dose through randomized and exploratory cohorts. Participants will be closely monitored for their response to the treatment and any potential side effects.

Who should consider this trial

Good fit: Ideal candidates for this study are patients with advanced or metastatic breast cancer who have specific HER2 expression profiles.

Not a fit: Patients with uncontrolled intercurrent illnesses or recent history of small bowel obstruction may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new effective treatment option for patients with advanced breast cancer.

How similar studies have performed: Other studies have shown promise with similar combination therapies, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion 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.

Key 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.

Where this trial is running

Beverly Hills, California and 38 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Locally Advanced Breast CancerUnresectable Breast CarcinomaMetastatic Breast CancerBreast CancerHuman epidermal growth factor receptor 2IHC scores 0, 1+, 2+, and 3+Antibody drug conjugateProgrammed Death-1
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.