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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

BioNTech SE

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 Mar 2026 → ongoing

Decision date (initial)

2025-11-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-517979-20-00

ClinicalTrials.gov

NCT06827236

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Safety, Efficacy

Dose escalation (Part I): To determine the recommended Phase 2 dose (RP2D) of BNT323 in combination with BNT327 by assessing safety.
Dose optimization (Part II): To assess the efficacy and safety of BNT323 monotherapy, BNT327 monotherapy, and BNT323 in combination with BNT327 in terms of objective response rate (ORR).

Secondary objectives 3

1. Dose escalation (Part I): To assess the efficacy of BNT323 in combination with BNT327 in terms of ORR, according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) assessed by the investigator.
2. Dose optimization (Part II): To evaluate the efficacy (other than ORR) of BNT323 monotherapy, BNT327 monotherapy, and BNT323 in combination with BNT327.
3. Dose optimization (Part II): Cohort 1 only: To evaluate the efficacy of BNT323 monotherapy, BNT327 monotherapy, and BNT323 in combination with BNT327 in terms of progression free survival (PFS).

Conditions and MedDRA coding

Advanced Breast Cancer Metastatic Breast Cancer

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

EMA paediatric investigation plan (PIP)

EMEA-003599-PIP01-24

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Have pathologically documented breast cancer (BC) that: is locally advanced, unresectable or metastatic; has a confirmed human epidermal growth factor receptor 2 (HER2) status as determined by the local laboratory (Part I, Part 2 Cohorts 2 and 4) or the central laboratory (Part II 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
2. Have measurable disease defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
3. Has left ventricular ejection fraction (LVEF) greater than or equal to 55% by either echocardiography (ECHO) or multi-gated acquisition (MUGA) within 28 days before randomization/enrollment

Exclusion criteria 9

1. Have history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP
2. Have an uncontrolled intercurrent illness that would limit compliance with trial requirement or substantially increase risk of incurring adverse events (AEs)
3. 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.
4. Have a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroid, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
5. Had prior treatment with topoisomerase I inhibitors, including antibody-drug conjugate (ADCs) with topoisomerase I inhibitor payloads such as trastuzumab deruxtecan (T-DXd)
6. Participants who have previously been randomized to or received treatment in a previous trial with BNT323, regardless of treatment assignment
7. Participants who received prior treatment with a programmed death 1/ vascular endothelial growth factor (PD-L1/VEGF) bispecific antibody
8. Participants who have received other systemic immunostimulatory agents or immunosuppressive therapies within 4 weeks prior to the initiation of trial treatment or are within five half-lives of the treatment drug (whichever is longer)
9. Participants who 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 trial treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Part 1 - Occurrence of dose limiting toxicities (DLTs) during the DLT evaluation period (Cycle 1), by dose level.
2. Occurrence of Treatment-emergent adverse events (TEAEs), Grade greater than or equal to 3 TEAEs, serious adverse events (SAEs), treatment-related TEAEs, treatment-related Grade greater than or equal to 3 TEAEs, and treatment-related SAEs. In Part 1 by dose level. In Part 2 by cohort and arm.
3. Occurrence of dose interruption, reduction, and discontinuation due to TEAEs In Part 1 by dose level. In Part 2 by cohort and arm.
4. Part 2 - Objective response rate (ORR) defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) is observed as best overall response, by cohort and arm.

Secondary endpoints 5

1. Part 1 - ORR defined as the proportion of participants in whom a confirmed CR or PR is observed as best overall response, by dose level.
2. Part 2 - Duration of response (DoR) defined as the time from first objective response to first occurrence of objective tumor progression or death from any cause, whichever occurs first, by cohort and arm.
3. Part 2 - Disease control rate (DCR) defined as the proportion of participants with confirmed CR, PR, or stable disease as best overall response, by cohort and arm.
4. Part 2 - Time to response (TTR) defined as the time from first dose of IMP to first objective response, by cohort and arm.
5. Part 2 Cohort 1 only - Progression free survival (PFS) based on the investigator’s assessment defined as the time from first dose of IMP to the first objective tumor progression or death from any cause, whichever occurs first, by arm.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

BioNTech SE

Sponsor organisation

BioNTech SE

Address

An Der Goldgrube 12, Oberstadt Oberstadt

City

Mainz

Postcode

55131

Country

Germany

Scientific contact point

Organisation

BioNTech SE

Contact name

Clinical Trial Information Desk

Public contact point

Organisation

BioNTech SE

Contact name

Clinical Trial Information Desk

Third parties 8

Locations

3 EU/EEA countries · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 43 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications