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RecruitingLast updated: 18 May 2026

Fern-EC-01: This study is recruiting people with previously treated endometrial cancer to investigate how well a drug called BNT323 works compared to chemotherapyA Phase III, Randomized, Multi-site, Open-label Trial of BNT323/DB-1303 Versus Investigator's Choice of Chemotherapy in Previously Treated Patients With HER2- Expressing Recurrent Endometrial Cancer

Trial purpose

Medical clipboardCancer treatment

Tumor type

Female Reproductive System Cancers Gynaecological

Age

People18+

Trial acronym

Fern-EC-01

Clinical summary

Summary

This study is looking at a new treatment called BNT323 (also known as DB-1303) for people with recurrent endometrial cancer - meaning the cancer has come back after earlier treatment. Everyone joining the study should have already been treated with at least one type of platinum-based chemotherapy and an immune checkpoint inhibitor (ICI).

Participants are placed into one of two groups (cohorts) based on how much HER2, a protein on cancer cells, is found in their tumour sample. This is measured using a test called IHC (immunohistochemistry).

Cohort 1: People with HER2 IHC 1+ or 2
The group will compare how well BNT323 works versus standard chemotherapy. Participants will be randomly assigned (by chance) to receive one of two treatments:

  • BNT323 or
  • standard chemotherapy (doxorubicin or paclitaxel; docetaxel may be used if paclitaxel isn't suitable)

The main goal is to measure progression-free survival, meaning how long people live without their cancer getting worse.

Cohort 2: HER2 IHC3+
This group will assess how well BNT323 works by looking at how many people have their tumours shrink or disappear after treatment. This is called the objective response rate. All participants in this cohort will receive BNT323. 

For both cohorts, the study consists of a screening period, a treatment period, a safety follow-up period, an efficacy follow-up period, and a long-term follow-up. The expected treatment duration per participant is ~6 months, followed by an anticipated long-term survival follow-up period of up to 53 months.

 

 

Conditions

This trial is treating people with recurrent HER2 expressing endometrial cancer

Eligibility

Inclusion

  • Are female adults (defined as ≥18 years of age or acceptable age according to local regulations at the time of voluntarily giving informed consent).
  • 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 (i.e., leiomyosarcoma or endometrial stromal sarcoma). Note: Uterine carcinosarcoma is allowed.
  • Have measurable disease defined by RECIST v1.1.
  • Have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
  • Have recurrent endometrial cancer and meet any of the following:

    • developed recurrence <12 months from completing platinum-based chemotherapy given as adjuvant therapy for Stage I to III disease, or
    • developed recurrence after platinum-based chemotherapy in the recurrent/metastatic setting.
  • Have received prior ICI treatment (i.e., anti-programmed death 1/anti-programmed death-ligand 1)
  • Have a life expectancy of ≥12 weeks at screening.

Exclusion

  • Are ineligible for all options in the investigator's choice of chemotherapy arm, per local prescribing information and institutional guidelines (applicable to Cohort 1 only).
  • Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior the first dose of study treatment.
  • 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, or peritoneal shunt within 2 weeks prior to the first dose of study treatment.
  • 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.
  • Participants with prior use of immunosuppressive medication within 14 days prior to the first dose of study treatment, except for intranasal and inhaled corticosteroids or systemic corticosteroids at doses of less than 10 mg/day of prednisone or equivalent, and topical corticosteroids. Participants receiving corticosteroids may continue if the dose is stable upon giving main informed consent.
  • Have a lung-specific intercurrent clinically significant illness including, but not limited to, any underlying pulmonary disorder (e.g., pulmonary emboli within 3 months prior to the first dose of study treatment, severe asthma, chronic obstructive pulmonary disorder with moderate acute exacerbations, restrictive lung disease, pulmonary fibrosis, radiation pneumonitis, significant pleural effusion etc.), or any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement (i.e., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis etc.), and/or prior pneumonectomy (complete).
  • Have uncontrolled infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks prior to the first dose of study treatment.
  • 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 baseline.
  • Are pregnant or breastfeeding or are planning pregnancy during the study or within 7 months after the last dose of study treatment.
  • Have a history of allergies, hypersensitivities, or intolerance to study treatments (investigational medicinal products and auxiliary medicinal product) 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.
  • Had prior treatment with topoisomerase I inhibitors, including ADCs.
  • Have left ventricular ejection fraction <55% by either echocardiography or multiple-gated acquisition within 28 days prior to the first dose of study treatment. This includes participants with tissue doppler E/e' ratio >15.

NOTE: Other protocol defined Inclusion/Exclusion criteria apply.

Inclusion

  • You have had treatment, but your cancer has come back (relapsed or recurrent).
  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
  • You have had a certain type of treatment or surgical procedure.

Exclusion

  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

Participating hospitals

Recruiting hospitals

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More information

Trial Identifiers

Information on this page is partially produced from ClinicalTrials.gov, EU Clinical Trials Register *. View further details about this trial on the registry via the links below:

  • NCT06340568 *
  • 2023-507525-42-00 *
  • BNT323-01; GOG-3105; ENGOT- EN25/NSGO-CTU

Trial sponsor

BioNTech SE

Scientific Title

A Phase III, Randomized, Multi-site, Open-label Trial of BNT323/DB-1303 Versus Investigator's Choice of Chemotherapy in Previously Treated Patients With HER2- Expressing Recurrent Endometrial Cancer

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