A clinical study of the anti-cancer effects of an investigational therapy or chemotherapy in patients with recurring uterine cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

BioNTech SE

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Trial duration

23 Dec 2025 → ongoing

Decision date (initial)

2025-11-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-507525-42-00

ClinicalTrials.gov

NCT06340568

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Cohort 1, participants with HER2 IHC 1+/2+ recurrent endometrial cancer:
To assess the efficacy of BNT323 compared to investigator’s choice of chemotherapy in terms of a hazard ratio (HR) for progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by blinded independent central review (BICR) in participants with human epidermal growth factor receptor 2 (HER2) IHC 1+/2+ recurrent endometrial cancer.

Cohort 2, participants with HER2 IHC 3+ recurrent endometrial cancer:
To assess the efficacy of BNT323 in terms of objective response rate (ORR) according to RECIST 1.1 assessed by blinded independent central review (BICR) in participants with HER2 IHC 3+ recurrent endometrial cancer.

Secondary objectives 9

1. Cohort 1: To assess the efficacy of BNT323 followed by any other subsequent anticancer therapy compared to investigator’s choice of chemotherapy followed by any other subsequent anti-cancer therapy in terms of a hazard ratio (HR) for overall survival (OS) in participants with HER2 IHC 1+/2+ recurrent endometrial cancer.
2. Cohort 1: To assess the efficacy of BNT323 compared to investigator’s choice of chemotherapy a in terms of progression-free survival (PFS) according to RECIST 1.1 assessed by the investigator.
3. Cohort 1: To assess the efficacy of BNT323 compared to investigator’s choice of chemotherapy a in terms of ORR and duration of response (DoR) according to RECIST 1.1 assessed by BICR and the investigator.
4. Cohort 1: To assess the safety and tolerability profile of BNT323.
5. Cohort 2: To assess the efficacy of BNT323 in terms of ORR according to RECIST 1.1 assessed by investigator.
6. Cohort 2: To assess the efficacy of BNT323 in terms of DoR according to RECIST 1.1 assessed by BICR and investigator.
7. Cohort 2: To assess the efficacy of BNT323 in terms of progression-free survival (PFS) according to RECIST 1.1 assessed by BICR and investigator.
8. Cohort 2: To assess the efficacy of BNT323 in terms of overall survival (OS).
9. Cohort 2: To assess the safety and tolerability profile of BNT323.

Conditions and MedDRA coding

Endometrial cancer

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

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 8

1. Are female adults.
2. Have histologically confirmed endometrial cancer that: − is recurrent, − has a HER2 IHC score of 1+, 2+ (Cohort 1), or 3+ (Cohort 2) as determined by central laboratory testing for HER2 expression, and − is not defined as a true sarcoma.
3. Have measurable disease defined by RECIST 1.1.
4. Have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
5. Have recurrent endometrial cancer and meet any of the following: -developed recurrence within less than 12 months from completing platinum-based chemotherapy as adjuvant therapy for Stage I to III disease, or -developed recurrence after platinum-based chemotherapy in the recurrent / metastatic setting.
6. Have a life expectancy of 12 weeks or longer at screening.
7. Have received prior immune-checkpoint inhibitor (ICI) treatment (i.e., anti-PD-1/anti-PD-L1).
8. Up to three lines of prior therapy are allowed.

Exclusion criteria 13

1. Are ineligible for all options in the investigator’s choice chemotherapy arm, per local prescribing information and institutional guidelines (applicable to Cohort 1 only).
2. Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of trial treatment.
3. Have an uncontrolled intercurrent illness that would limit compliance with study requirement or substantially increase risk of incurring adverse events.
4. Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, or peritoneal shunt within 2 weeks prior to the first dose of trial treatment.
5. 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.
6. Participants with prior use of immunosuppressive medication within 14 days prior to the first dose of trial treatment, except for intranasal and inhaled corticosteroids or systemic corticosteroids at doses of less than 10 mg/day of prednisone or equivalent. Participants receiving corticosteroids may continue if the dose is stable upon giving main informed consent.
7. Have a lung-specific intercurrent clinically significant illness including, but not limited to, any underlying pulmonary disorder, or any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement, and/or prior pneumonectomy (complete).
8. Have uncontrolled infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks prior to the first dose of trial treatment.
9. Have unresolved toxicities from previous anti-cancer therapy, defined as toxicities (other than alopecia, fatigue, or endocrinopathies that are well controlled) not yet resolved to Grade 1 or below, or baseline.
10. Are pregnant or breastfeeding or are planning pregnancy during the study or within 7 months after the last dose of study treatment.
11. Have a history of allergies, hypersensitivities, or intolerance to trial treatments including any excipients thereof or to other monoclonal antibodies. Participants who have successfully undergone a desensitization process and are able to tolerate the drug are eligible.
12. Had prior treatment with topoisomerase I inhibitors, including antibody-drug conjugates (ADCs).
13. Have left ventricular ejection fraction (LVEF) below 55% by either echocardiography (ECHO) or multiple-gated acquisition (MUGA) within 28 days prior to the first dose of trial treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Cohort 1: By treatment arm, PFS by BICR defined as the time from randomization to the first objective tumor progression (per RECIST 1.1) or death from any cause, whichever occurs first.
2. Cohort 2: For BNT323 monotherapy, objective response rate (ORR) assessed by blinded independent central review (BICR), defined as the proportion of participants with a complete response (CR) or partial response (PR) (per RECIST 1.1) as best overall response with confirmation.

Secondary endpoints 12

1. Cohort 1, by treatment arm: overall survival (OS) defined as the time from randomization to death from any cause.
2. Cohort 1, by treatment arm: PFS assessed by the investigator defined as the time from randomization to the first objective tumor progression (per RECIST 1.1) or death from any cause, whichever occurs first.
3. Cohort 1, by treatment arm: Objective response rate (ORR) defined as the proportion of participants with a complete response (CR) or partial response (PR) (per RECIST 1.1) as best overall response with confirmation.
4. Cohort 1, by treatment arm: Duration of response (DoR) defined as the time from first objective response (CR or PR per RECIST 1.1) to first occurrence of objective tumor progression (progressive disease [PD] per RECIST 1.1) or death from any cause, whichever occurs first.
5. Cohort 1, by treatment arm: Occurrence of treatment-emergent adverse events (TEAEs) including Grade ≥3, serious, and fatal TEAEs by relationship from the time of initiation of the first dose of trial treatment to 35 days after the last trial treatment dose.
6. Cohort 1, by treatment arm: Occurrences of TEAEs leading to drug interruption, dose reduction, or discontinuation of trial treatment.
7. For Cohort 2, for BNT323 monotherapy: ORR assessed by the investigator, defined as the proportion of participants with a CR or PR (per RECIST 1.1) as best overall response with confirmation.
8. For Cohort 2, for BNT323 monotherapy: DoR defined as the time from first objective response (CR or PR per RECIST 1.1) to first occurrence of objective tumor progression (PD per RECIST 1.1) or death from any cause, whichever occurs first.
9. For Cohort 2, for BNT323 monotherapy: PFS defined as the time from the first dose of trial treatment to the first objective tumor progression (per RECIST 1.1) or death from any cause, whichever occurs first.
10. For Cohort 2, for BNT323 monotherapy: OS defined as the time from the first dose of trial treatment to death from any cause.
11. For Cohort 2, for BNT323 monotherapy: Occurrence of treatment-emergent adverse events (TEAEs) including Grade ≥3, serious, and fatal TEAEs by relationship from the time of initiation of the first dose of trial treatment to 35 days after the last trial treatment dose.
12. For Cohort 2, for BNT323 monotherapy: Occurrences of TEAEs leading to drug interruption, dose reduction, or discontinuation of trial treatment.

Investigational products

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

Test 1

Comparator 3

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 13

Locations

15 EU/EEA countries · 86 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 147 files

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

Application history

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