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Treatment of recurring uterine (endometrial) cancer with the investigational drug BNT323 or chemotherapy

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

Phase 3 Interventional BioNTech SE · NCT06340568

This study tests whether the investigational drug BNT323 works better than single-agent chemotherapy for people with recurrent HER2-expressing endometrial cancer who have had platinum chemotherapy and immune checkpoint inhibitors, and also examines BNT323 alone for tumors with very high HER2 expression.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment480 (estimated)
Ages18 Years and up
SexFemale
SponsorBioNTech SE Industry-sponsored
Drugs / interventionschemotherapy, radiation, prednisone, doxorubicin
Locations132 sites (Washington D.C., District of Columbia and 131 other locations)
Trial IDNCT06340568 on ClinicalTrials.gov

What this trial studies

This is an open-label, randomized, multi-site Phase 3 study comparing BNT323 with investigator's choice single-agent chemotherapy in patients with recurrent endometrial cancer who have HER2 IHC 1+ or 2+ and prior platinum and immune checkpoint inhibitor treatment (Cohort 1). Cohort 1 participants are randomized 2:1 to receive BNT323 or doxorubicin/paclitaxel (or docetaxel if paclitaxel is contraindicated) until RECIST v1.1 progression or unacceptable toxicity. Cohort 2 enrolls patients with HER2 IHC 3+ to receive BNT323 monotherapy and measures objective response rate. Safety and pharmacokinetics of BNT323 are monitored throughout treatment, with follow-up periods for safety, efficacy, and long-term survival.

Who should consider this trial

Good fit: Adult women with recurrent, measurable endometrial cancer who have HER2 IHC 1+ or 2+ (for the randomized cohort) or 3+ (for the monotherapy cohort), ECOG 0–2, and prior platinum chemotherapy and immune checkpoint inhibitor therapy are the intended participants.

Not a fit: Patients whose tumors do not express HER2, patients with true uterine sarcomas, or those who have not had prior platinum and ICI therapy are unlikely to be eligible or to benefit from this protocol.

Why it matters

Potential benefit: If successful, BNT323 could shrink tumors or delay disease progression more effectively than standard single-agent chemotherapy in HER2-expressing recurrent endometrial cancer.

How similar studies have performed: Other HER2-targeted therapies such as trastuzumab have shown benefit in certain HER2-positive endometrial cancers, but BNT323 is a novel agent and its effectiveness in this setting is still unproven.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria:

* 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.

Key Exclusion Criteria:

* 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.

Where this trial is running

Washington D.C., District of Columbia and 131 other locations

+82 more sites — see ClinicalTrials.gov for the full list.

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 Endometrial CancerHuman epidermal growth factor receptor 2HER2-expressing tumorsRecurrent endometrial cancerIHC scores 1+, 2+, and 3+Immune checkpoint inhibitorPlatinum-based therapyHER2 protein expression
Last reviewed 2026-06-10 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.