A Clinical Study of the Anti-cancer Effects of an Investigational Therapy or Chemotherapy in Patients With Recurring Uterine Cancer (Fern-EC-01)

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

The study is divided into two cohorts (Cohort 1 and Cohort 2), to which participants will be enrolled based on the amount of human epidermal growth factor receptor 2 (HER2) in their tumor sample.

In Cohort 1, the main goal is to assess how well BNT323 (also known as DB-1303) or chemotherapy (doxorubicin or paclitaxel [or docetaxel, if participants cannot take paclitaxel]) works by determining the progression-free survival (PFS) of participants who have been previously treated with immune checkpoint inhibitors (ICIs).

In Cohort 2, the main goal is to assess how well BNT323 works by determining the objective response rate (ORR), that is, the percentage of participants whose tumor shrinks (partial response) or disappears (complete response) after treatment.

The safety of BNT323 will also be assessed by following the occurrence of unfavorable/adverse effects that are seen after treatment. Other measures include the pharmacokinetics of BNT323 (or how BNT323 moves through and out of the body), the body's immune response, and the impact on quality of life.

Study Overview

• Status: Recruiting
• Conditions: Endometrial Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: Paclitaxel; Drug: BNT323/DB-1303; Drug: Doxorubicin

Detailed Description

This is an open-label, randomized, multi-site, Phase III, interventional clinical study designed to determine the efficacy and safety of BNT323 compared with investigator's choice of single agent chemotherapy in previously treated participants with recurrent endometrial cancer (including HER2 1+ or 2+ score as determined using a centralized immunohistochemistry [IHC] analysis method), whose disease has progressed on at least one line of platinum-based therapy and ICI (Cohort 1). In addition, participants with recurrent endometrial cancer with HER2 IHC 3+ score will be enrolled in a BNT323 monotherapy arm (Cohort 2) to further investigate the efficacy and safety of BNT323.

In Cohort 1, participants will be randomized 2:1 to receive either BNT323/DB-1303 or investigator's choice of single agent chemotherapy, preferably doxorubicin or paclitaxel (or docetaxel if contraindicated to paclitaxel and available at the site) until Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) defined progressive disease (PD) unless there is unacceptable toxicity, withdrawal of consent, or another criterion for discontinuation is met.

In Cohort 2, participants will receive BNT323 monotherapy until RECIST v1.1 defined PD unless there is unacceptable toxicity, withdrawal of consent, or another criterion for discontinuation is met.

The study consists of a screening period, a treatment period, a safety follow-up period, an efficacy follow-up period, and a long-term survival 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.

• Study Type: Interventional
• Enrollment (Estimated): 480
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: BioNTech clinical trials patient information; Phone Number: +49 6131 9084; Email: patients@biontech.de

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1280AEB
    • Recruiting
    • Hospital Britanico de Buenos Aires
  • La Rioja, Argentina, F5300COE
    • Recruiting
    • Investigaciones CORI S.R.L.
  • Rosario, Argentina, S2002KDS
    • Recruiting
    • Hospital Provincial del Centenario
  • San Juan, Argentina, 5400
    • Recruiting
    • Centro Oncológico de Excelencia
• Australia
  • Adelaide, Australia, 5000
    • Recruiting
    • Cancer Research SA
  • Adelaide, Australia, 5000
    • Recruiting
    • Adelaide Oncology & Haematology
  • Clayton, Australia, 3168
    • Recruiting
    • Monash Health Clinical Trial Center
  • Gosford, Australia, 2250
    • Recruiting
    • Gosford Hospital
  • Melbourne, Australia, 3000
    • Recruiting
    • Peter MacCallum Cancer Centre
  • Melbourne, Australia, VIC 3199
    • Recruiting
    • Frankston Hospital
  • Nowra, Australia, 2541
    • Recruiting
    • Shoalhaven Cancer Care Centre
  • Saint Albans, Australia, 3021
    • Recruiting
    • Sunshine Hospital
  • South Brisbane, Australia, 4001
    • Recruiting
    • Mater Hospital Brisbane
  • Wollongong, Australia, 2500
    • Recruiting
    • Wollongong Hospital
• Belgium
  • Brussels, Belgium, 1070
    • Recruiting
    • Institut Jules Bordet
  • Ghent, Belgium, 9000
    • Recruiting
    • Universitair Ziekenhuis Gent
  • Kortrijk, Belgium, 8500
    • Recruiting
    • AZ Groeninge vzw
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Leuven
  • Namur, Belgium, B5000
    • Recruiting
    • CHU UCL Namur-Sainte-Elisabeth
• Brazil
  • Ipatinga, Brazil, 35162-189
    • Recruiting
    • Fundacao Sao Francisco Xavier
  • Passo Fundo, Brazil, 99010-260
    • Recruiting
    • Hospital de Clinicas de Passo Fundo
  • Porto Alegre, Brazil, 90050-170
    • Recruiting
    • Irmandade da Santa Casa de Misericordia de Porto Alegre
  • Porto Alegre, Brazil, 90035-903
    • Recruiting
    • Hospital De Clinicas De Porto Alegre
  • Porto Alegre, Brazil, 90035-000
    • Recruiting
    • Instituto de Pesquisa Clínica - Hospital Moinhos de Vento
  • Porto Alegre, Brazil, 90610-000
    • Recruiting
    • HPT São Lucas da PUCRS - UBEA
  • São José do Rio Preto, Brazil, 15090-000
    • Recruiting
    • Fundação Faculdade Regional de Medicina de São José do Rio Petro
  • São Paulo, Brazil, 01308-050
    • Recruiting
    • Hospital Sirio Libanes
  • São Paulo, Brazil, 01401-002
    • Recruiting
    • Inst D'Or de Pesquisa E Ensino
• Canada
  • Montreal, Canada, H3T 1E2
    • Recruiting
    • Jewish General Hospital
  • St. John's, Canada, A1V 3V6
    • Recruiting
    • Health Sciences Centre
  • Toronto, Canada, M5G 2M9
    • Recruiting
    • Princess Margaret Cancer C
• China
  • Anhui
    • Hefei, Anhui, China, 230001
      • Recruiting
      • Anhui Provincial Hospital
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400010
      • Recruiting
      • The Second Affiliated Hospital of Chongqing Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Recruiting
      • Fujian Provincial Cancer Hospital
    • Xiamen, Fujian, China, 361003
      • Recruiting
      • First Affiliated Hospital of Xiamen University
  • Gansu
    • Lanzhou, Gansu, China, 730050
      • Recruiting
      • Gansu Provincial Maternity and Child-care Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • The First Affiliated Hospital of Sun Yat-Sen University
    • Shantou, Guangdong, China, 515063
      • Recruiting
      • Cancer Hospital of Shantou University Medical College
  • Guangxi
    • Nanning, Guangxi, China, 530200
      • Recruiting
      • Guangxi Medical University Affiliated Tumor Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150091
      • Recruiting
      • Harbin medical university cancer hospital
  • Henan
    • Zhengzhou, Henan, China, 450014
      • Recruiting
      • The Second Affiliated Hospital of Zhengzhou University
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Recruiting
      • Hubei Cancer Hospital
    • Xiangyang, Hubei, China, 441138
      • Recruiting
      • Xiangyang Central Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Recruiting
      • The Affiliated Hospital of Nanjing University Medical School
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Recruiting
      • Jiangxi Maternal and Child Health Hospital
  • Jilin
    • Changchun, Jilin, China, 130021
      • Recruiting
      • The First Hospital of Jilin University
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • Recruiting
      • The First Affiliated Hospital of Xian Jiaotong University
  • Shandong
    • Jinan, Shandong, China, 250117
      • Recruiting
      • Cancer Hospital of Shandong First Medical University
    • Jining, Shandong, China, 272029
      • Recruiting
      • Affiliated Hospital of Jining Medical University
    • Linyi, Shandong, China, 276001
      • Recruiting
      • Linyi Cancer Hospital
    • Yantai, Shandong, China, 264000
      • Recruiting
      • Yantai Yuhuangding Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai Municipality, China, 200011
      • Recruiting
      • Obstetrics & Gynecology Hospital of Fudan University
  • Sichuan
    • Chengdu, Sichuan, China, 610072
      • Recruiting
      • Sichuan Provincial People's Hospital
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300060
      • Recruiting
      • Tianjin Medical University Cancer Institute & Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Recruiting
      • Zhejiang Cancer Hospital
    • Wenzhou, Zhejiang, China, 325015
      • Recruiting
      • The First Affiliated Hospital of Wenzhou Medical University
• Czechia
  • Brno, Czechia, 60200
    • Recruiting
    • Gynekologicko-porodnická klinika, Fakultni nemocnice Brno
  • Olomouc, Czechia, 77900
    • Recruiting
    • University Hospital Olomouc - Onkologická klinika- Fakultni
  • Prague, Czechia, 15000
    • Recruiting
    • Fakultni Nemocnice Motol a Homolka
  • Prague, Czechia, 18081
    • Recruiting
    • Fakultni nemocnice Bulovka
• Denmark
  • Aalborg, Denmark, 9000
    • Recruiting
    • Aalborg Universit Hospital
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Rigshospitalet
  • Herlev, Denmark, 2730
    • Recruiting
    • Herlev og Gentofte Hospital
  • Odense, Denmark, 5000
    • Recruiting
    • Odense University Hospital
• Finland
  • Kuopio, Finland, 70210
    • Recruiting
    • Kuopio University HPT
  • Oulu, Finland, 90029
    • Recruiting
    • OYS Naisten poliklinikka
• France
  • Angers, France, 49055
    • Recruiting
    • ICO - Site Paul Papin
  • Besançon, France, 25000
    • Recruiting
    • CHU Besançon Service Oncologie
  • Caen, France, 14000
    • Recruiting
    • Centre Francois Baclesse
  • Le Mans, France, 72000
    • Recruiting
    • Clinique Victor Hugo - Centre Jean Bernard
  • Marseille, France, 13015
    • Recruiting
    • Hôpital Nord Bâtiment Mistral
  • Paris, France, 75010
    • Recruiting
    • Hopital Saint Louis
  • Saint-Herblain, France, 44800
    • Recruiting
    • ICO - Site René Gauducheau
  • Strasbourg, France, 67000
    • Recruiting
    • Institut de Cancérologie de Strasbourg Europe - ICANS
• Greece
  • Athens, Greece, 11528
    • Recruiting
    • Alexandra General Hospital of Athens
  • Athens, Greece, 11528
    • Recruiting
    • Aretaieio Hospital
  • Chaïdári, Greece, 124 62
    • Recruiting
    • University General Hospital Attikon
  • Kalamata, Greece, 24100
    • Recruiting
    • General Hospital of Kalamata
  • Marousi, Greece, 151 23
    • Recruiting
    • Iaso General Clinic
• Hungary
  • Debrecen, Hungary, 4032
    • Recruiting
    • Debreceni Egyetem
  • Kecskemét, Hungary, 6000
    • Recruiting
    • Bács-Kiskun Vármegyei Oktatókórház
• Israel
  • Haifa, Israel, 3436212
    • Recruiting
    • Lady Davis Carmel Medical Center
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Hadassah Ein Kerem Medical Center
  • Petah Tikva, Israel, 4941492
    • Recruiting
    • Rabin Medical Center-Beilinson Campus
  • Ramat Gan, Israel, 5265601
    • Recruiting
    • Sheba Medical Center
• Italy
  • Bari, Italy, 70124
    • Recruiting
    • Istituto Tumori Giovanni Paolo Ii Irccs Ospedale Oncologico Bari
  • Catania, Italy, 95126
    • Recruiting
    • Azienda Ospedaliera Cannizzaro - Oncologia
  • Meldola, Italy, 47014
    • Recruiting
    • IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST)
  • Milan, Italy, 20132
    • Recruiting
    • Ospedale San Raffaele
  • Milan, Italy, 20133
    • Recruiting
    • Istituto Nazionale dei Tumori
  • Milan, Italy, 20141
    • Recruiting
    • Istituto Europeo di Oncologia
  • Milan, Italy, 20159
    • Recruiting
    • Humanitas San Pio X
  • Naples, Italy, 80131
    • Recruiting
    • Istituto Nazionale Tumori Fondazione G. Pascale
  • Roma, Italy, 00168
    • Recruiting
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  • Torino, Italy, 10128
    • Recruiting
    • Azienda Ospedaliera Ordine Mauriziano Umberto I di Torino
• Netherlands
  • Nijmegen, Netherlands, 6525 GA
    • Recruiting
    • Radboud UMC
  • Rotterdam, Netherlands, 3015 AA
    • Recruiting
    • Erasmus Medisch Centrum
• Norway
  • Oslo, Norway, 0379
    • Recruiting
    • Oslo University Hospital
  • Stavanger, Norway, 4011
    • Recruiting
    • Stavanger University Hospital
• Poland
  • Bialystok, Poland, 15-027
    • Recruiting
    • Bialostockie Centrum Onkologii im. Marii Sklodowskiej-Curie
  • Siedlce, Poland, 08-110
    • Recruiting
    • Siedleckie Centrum Onkologii
• South Korea
  • Changwon, South Korea, 51353
    • Recruiting
    • Samsung Changwon Hospital
  • Daegu, South Korea, 42601
    • Recruiting
    • Keimyung Univty Dongsan Hospital
  • Goyang, South Korea, 10408
    • Recruiting
    • National Cancer Center
  • Seongnam, South Korea, 13620
    • Recruiting
    • Seoul National University Bundang Hospital
  • Seongnam-si, South Korea, 13496
    • Recruiting
    • CHA Bundang Medical Center
  • Seoul, South Korea, 05505
    • Recruiting
    • Asan Medical Center
  • Seoul, South Korea, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, South Korea, 03722
    • Recruiting
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 06351
    • Recruiting
    • Samsung Medical Center
  • Seoul, South Korea, 02841
    • Recruiting
    • Korea University Anam Hospital
  • Seoul, South Korea, 06591
    • Recruiting
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Seoul, South Korea, 07804
    • Recruiting
    • Ewha Womans University Seoul Hospital
  • Seoul, South Korea, 06273
    • Recruiting
    • Gangnam Severance Hospital, Yonsei University Health System
• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall, d'Hebron
  • Córdoba, Spain, 14004
    • Recruiting
    • Hospital Universitario Reina Sofia
  • Girona, Spain, 17007
    • Recruiting
    • Institut Català d'Oncologia (ICO) Hospital Universitari de Girona Dr. Josep Trueta
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
  • Valencia, Spain, 46009
    • Recruiting
    • Instituto Valenciano de Oncología - Valencia
• Sweden
  • Lund, Sweden, 222 42
    • Recruiting
    • Skånes Universitetssjukhus Lund
  • Stockholm, Sweden, 17176
    • Recruiting
    • Karolinska University Hospital
• Taiwan
  • Taichung, Taiwan, 40705
    • Recruiting
    • Taichung Veterans General Hospital
  • Taichung, Taiwan, 40447
    • Recruiting
    • China Medical University Hospital
  • Taichung, Taiwan, 433004
    • Recruiting
    • Kuang Tien General Hospital
  • Tainan, Taiwan, 70457
    • Recruiting
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 11217
    • Recruiting
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 10449
    • Recruiting
    • MacKay Memorial Hospital_ Taipei Branch
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01120
    • Recruiting
    • Baskent University Adana Application and Research Center
  • Ankara, Turkey (Türkiye), 06490
    • Recruiting
    • Baskent University Ankara Hospital
  • Ankara, Turkey (Türkiye), 06200
    • Recruiting
    • Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital
  • Ankara, Turkey (Türkiye), 06230
    • Recruiting
    • Hacettepe University
  • Istanbul, Turkey (Türkiye), 34093
    • Recruiting
    • Bezmialem Vakif Universitesi Tip Fakultesi Hastanesi
• United Kingdom
  • Brighton, United Kingdom, BN2 1ES
    • Recruiting
    • Royal Sussex County Hospital
  • Bristol, United Kingdom, BS2 8ED
    • Recruiting
    • Bristol Haematology and Oncology Centre
  • Cambridge, United Kingdom, CB2 0QQ
    • Recruiting
    • Addenbrooke's Hospital
  • Cottingham, United Kingdom, HU165JQ
    • Recruiting
    • Castle Hill Hospital
  • Edinburgh, United Kingdom, EH4 2XU
    • Recruiting
    • Western General Hospital
  • Exeter, United Kingdom, EX2 5DW
    • Recruiting
    • Royal Devon & Exeter HPT
  • London, United Kingdom, SE1 9RT
    • Recruiting
    • Guy's Hospital
  • London, United Kingdom, NW1 2PG
    • Recruiting
    • University College London Hospitals
  • Middlesex, United Kingdom, HA6 2RN
    • Recruiting
    • Mount Vermont Cancer Center
  • Nottingham, United Kingdom, NG5 1PB
    • Recruiting
    • Nottingham University Hospitals NHS Trust
  • Swansea, United Kingdom, SA2 8QA
    • Recruiting
    • Singleton Hospital
  • Truro, United Kingdom, TR1 3LJ
    • Recruiting
    • Royal Cornwall Hospital
• United States
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Recruiting
      • Medstar Washington Hospital Center
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Recruiting
      • Broward Health Medical Center
  • Nevada
    • Reno, Nevada, United States, 89511
      • Recruiting
      • The Center of Hope Reno
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health
  • Ohio
    • Centerville, Ohio, United States, 45459
      • Recruiting
      • Miami Valley Hospital South
    • Hilliard, Ohio, United States, 43026
      • Recruiting
      • Ohio State University
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Recruiting
      • Sanford Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (HER2 IHC score 1+ or 2+): BNT323/DB-1303	Drug: BNT323/DB-1303; intravenous (IV) infusion; Other Names: trastuzumab pamirtecan
Active Comparator: Cohort 1 - Doxorubicin or paclitaxel (or docetaxel); Single agent chemotherapy (either doxorubicin or paclitaxel) per investigator's choice. Participants with contraindications to paclitaxel may receive docetaxel as an alternative (if available at the site).	Drug: Docetaxel; IV infusion; Drug: Paclitaxel; IV infusion; Drug: Doxorubicin; IV bolus or infusion
Experimental: Cohort 2 (HER2 IHC score 3+) - BNT323/DB-1303	Drug: BNT323/DB-1303; intravenous (IV) infusion; Other Names: trastuzumab pamirtecan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort 1: PFS assessed by blinded independent central review (BICR) in participants with HER2 IHC 1+/2+ recurrent endometrial cancer	By treatment arm. Defined as the time from randomization to the first objective tumor progression (per RECIST v1.1) or death from any cause, whichever occurs first.	Up to approximately 53 months
Cohort 2: ORR assessed by BICR in participants with HER2 IHC 3+ recurrent endometrial cancer	Defined as the proportion of participants with a CR or PR (per RECIST v1.1) as best overall response with confirmation.	Up to approximately 53 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort 1: Overall survival (OS) in participants with HER2 IHC 1+/2+ recurrent endometrial cancer	By treatment arm. Defined as the time from randomization to death from any cause.	Up to approximately 53 months
Cohort 1: PFS assessed by the investigator in participants with HER2 IHC 1+/2+ recurrent endometrial cancer	By treatment arm. Defined as the time from randomization to the first objective tumor progression (per RECIST v1.1) or death from any cause, whichever occurs first.	Up to approximately 53 months
Cohort 1: ORR assessed by BICR in participants with HER2 IHC 1+/2+ recurrent endometrial cancer	By treatment arm. Defined as the proportion of participants with a CR or PR (per RECIST v1.1) as best overall response with confirmation.	Up to approximately 53 months
Cohort 1: ORR assessed by the investigator in participants with HER2 IHC 1+/2+ recurrent endometrial cancer	By treatment arm. Defined as the proportion of participants with a CR or PR (per RECIST v1.1) as best overall response with confirmation.	Up to approximately 53 months
Cohort 1: Duration of response (DoR) assessed by BICR in participants with HER2 IHC 1+/2+ recurrent endometrial cancer	By treatment arm. Defined as the time from first objective response (CR or PR per RECIST v1.1) to first occurrence of objective tumor progression (PD per RECIST v1.1) or death from any cause, whichever occurs first.	Up to approximately 53 months
Cohort 1: DoR assessed by the investigator in participants with HER2 IHC 1+/2+ recurrent endometrial cancer	By treatment arm. Defined as the time from first objective response (CR or PR per RECIST v1.1) to first occurrence of objective tumor progression (PD per RECIST v1.1) or death from any cause, whichever occurs first.	Up to approximately 53 months
Cohort 1: Percentage of participants with HER2 IHC 1+/2+ recurrent endometrial cancer with occurrence of treatment-emergent adverse events (TEAEs)	By treatment arm. TEAEs including Grade ≥3, serious, and fatal TEAEs by relationship.	Up to 35 days after the last dose of study treatment
Cohort 1: Percentage of participants with HER2 IHC 1+/2+ recurrent endometrial cancer with occurrence of TEAEs leading to drug interruption, dose reduction, or discontinuation of study treatment.	By treatment arm.	Up to 35 days after the last dose of study treatment
Cohort 2: ORR assessed by the investigator participants with HER2 IHC 3+ recurrent endometrial cancer	Defined as the proportion of participants in whom a CR or PR (per RECIST v1.1) is observed as best overall response with confirmation.	Up to approximately 53 months
Cohort 2: DoR assessed by BICR in participants with HER2 IHC 3+ recurrent endometrial cancer	Defined as the time from first objective response (CR or PR per RECIST v1.1) to first occurrence of objective tumor progression (PD per RECIST v1.1) or death from any cause, whichever occurs first.	Up to approximately 53 months
Cohort 2: DoR assessed by the investigator in participants with HER2 IHC 3+ recurrent endometrial cancer	Defined as the time from first objective response (CR or PR per RECIST v1.1) to first occurrence of objective tumor progression (PD per RECIST v1.1) or death from any cause, whichever occurs first.	Up to approximately 53 months
Cohort 2: PFS assessed by BICR in participants with HER2 IHC 3+ recurrent endometrial cancer	Defined as the time from the first dose of study treatment to the first objective tumor progression (per RECIST v1.1) or death from any cause, whichever occurs first.	Up to approximately 53 months
Cohort 2: PFS assessed by the investigator in participants with HER2 IHC 3+ recurrent endometrial cancer	Defined as the time from the first dose of study treatment to the first objective tumor progression (per RECIST v1.1) or death from any cause, whichever occurs first.	Up to approximately 53 months
Cohort 2: OS in participants with HER2 IHC 3+ recurrent endometrial cancer	Defined as the time from the first dose of trial treatment to death from any cause.	Up to approximately 53 months
Cohort 2: Percentage of participants with HER2 IHC 3+ recurrent endometrial cancer with occurrence of TEAEs	BNT323 monotherapy. TEAEs including Grade ≥3, serious, and fatal TEAEs by relationship.	Up to 35 days after the last dose of study treatment
Cohort 2: Percentage of participants with HER2 IHC 3+ recurrent endometrial cancer with occurrence of TEAEs leading to drug interruption, dose reduction, or discontinuation of study treatment.		Up to 35 days after the last dose of study treatment

Collaborators and Investigators

• Sponsor: BioNTech SE
• Collaborators: DualityBio Inc.; BioNTech (Shanghai) Pharmaceuticals Co., Ltd.
• Investigators: Study Director: BioNTech Responsible Person, BioNTech SE

Publications and helpful links

General Publications

• Secord AA, Powell MA, McAlpine J. Molecular Characterization and Clinical Implications of Endometrial Cancer. Obstet Gynecol. 2025 Nov 1;146(5):660-671. doi: 10.1097/AOG.0000000000006080. Epub 2025 Sep 18.

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): November 1, 2029

Study Registration Dates

• First Submitted: March 25, 2024
• First Submitted That Met QC Criteria: March 25, 2024
• First Posted (Actual): April 1, 2024

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Immune checkpoint inhibitor; Antibody drug conjugate (ADC); Platinum-based therapy; Human epidermal growth factor receptor 2 (HER2); HER2-expressing tumors; Recurrent endometrial cancer; IHC scores 1+, 2+, and 3+; HER2 protein expression; HER2-expressing endometrial cancer; ErbB-2 receptor
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Neoplasms; Endometrial Neoplasms; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Carbohydrates; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Taxoids; Cyclodecanes; Diterpenes; Anthracyclines; Naphthacenes; Aminoglycosides; Daunorubicin; Docetaxel; Doxorubicin; Paclitaxel
• Other Study ID Numbers: BNT323-01; GOG-3105 (Other Identifier: Gynecologic Oncology Group Foundation); 2023-507525-42-00 (Ctis: EU CT); ENGOT- EN25/NSGO-CTU (Other Identifier: European Network for Gynaecological Oncological Trial and Nordic Society of Gynaecological Oncology Clinical Trial Unit)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No