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
4 other identifiers
interventional
480
24 countries
156
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jun 2025
Typical duration for phase_3
156 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 25, 2024
CompletedFirst Posted
Study publicly available on registry
April 1, 2024
CompletedStudy Start
First participant enrolled
June 10, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
November 1, 2029
May 20, 2026
May 1, 2026
2.7 years
March 25, 2024
May 19, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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 Outcomes (16)
Cohort 1: Overall survival (OS) in participants with HER2 IHC 1+/2+ recurrent endometrial cancer
Up to approximately 53 months
Cohort 1: PFS assessed by the investigator in participants with HER2 IHC 1+/2+ recurrent endometrial cancer
Up to approximately 53 months
Cohort 1: ORR assessed by BICR in participants with HER2 IHC 1+/2+ recurrent endometrial cancer
Up to approximately 53 months
Cohort 1: ORR assessed by the investigator in participants with HER2 IHC 1+/2+ recurrent endometrial cancer
Up to approximately 53 months
Cohort 1: Duration of response (DoR) assessed by BICR in participants with HER2 IHC 1+/2+ recurrent endometrial cancer
Up to approximately 53 months
- +11 more secondary outcomes
Study Arms (3)
Cohort 1 (HER2 IHC score 1+ or 2+): BNT323/DB-1303
EXPERIMENTALCohort 1 - Doxorubicin or paclitaxel (or docetaxel)
ACTIVE COMPARATORSingle 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).
Cohort 2 (HER2 IHC score 3+) - BNT323/DB-1303
EXPERIMENTALInterventions
intravenous (IV) infusion
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- BioNTech SElead
- DualityBio Inc.collaborator
- BioNTech (Shanghai) Pharmaceuticals Co., Ltd.collaborator
Study Sites (156)
MedStar Washington Hospital Center
Washington D.C., District of Columbia, 20010, United States
Broward Health Medical Center
Fort Lauderdale, Florida, 33316, United States
The Center of Hope Reno
Reno, Nevada, 89511, United States
NYU Langone Health
New York, New York, 10016, United States
Miami Valley Hospital South
Centerville, Ohio, 45459, United States
Ohio State University
Hilliard, Ohio, 43026, United States
Sanford Cancer Center
Sioux Falls, South Dakota, 57104, United States
Hospital Británico de Buenos Aires
Buenos Aires, C1280AEB, Argentina
Investigaciones CORI S.R.L.
La Rioja, F5300COE, Argentina
Hospital Provincial del Centenario
Rosario, S2002KDS, Argentina
Centro Oncológico de Excelencia
San Juan, 5400, Argentina
Adelaide Oncology & Haematology
Adelaide, 5000, Australia
Cancer Research SA
Adelaide, 5000, Australia
Monash Health Clinical Trial Center
Clayton, 3168, Australia
Gosford Hospital
Gosford, 2250, Australia
Peter MacCallum Cancer Centre
Melbourne, 3000, Australia
Frankston Hospital
Melbourne, VIC 3199, Australia
Shoalhaven Cancer Care Centre
Nowra, 2541, Australia
Sunshine Hospital
Saint Albans, 3021, Australia
Mater Hospital Brisbane
South Brisbane, 4001, Australia
Wollongong Hospital
Wollongong, 2500, Australia
Institut Jules Bordet
Brussels, 1070, Belgium
Universitair Ziekenhuis Gent
Ghent, 9000, Belgium
AZ Groeninge VZW
Kortrijk, 8500, Belgium
UZ Leuven
Leuven, 3000, Belgium
CHU UCL Namur-Sainte-Elisabeth
Namur, B5000, Belgium
Fundação Sao Francisco Xavier
Ipatinga, 35162-189, Brazil
Hospital de Clínicas de Passo Fundo
Passo Fundo, 99010-260, Brazil
Instituto de Pesquisa Clínica - Hospital Moinhos de Vento
Porto Alegre, 90035-000, Brazil
Hospital de Clínicas de Porto Alegre
Porto Alegre, 90035-903, Brazil
Irmandade da Santa Casa de Misericórdia de Porto Alegre
Porto Alegre, 90050-170, Brazil
HPT São Lucas da PUCRS - UBEA
Porto Alegre, 90610-000, Brazil
Fundação Faculdade Regional de Medicina de São José do Rio Petro
São José do Rio Preto, 15090-000, Brazil
Hospital Sirio Libanês
São Paulo, 01308-050, Brazil
Inst D'Or de Pesquisa E Ensino
São Paulo, 01401-002, Brazil
Jewish General Hospital
Montreal, H3T 1E2, Canada
Health Sciences Centre
St. John's, A1V 3V6, Canada
Princess Margaret Cancer C
Toronto, M5G 2M9, Canada
Anhui Provincial Hospital
Hefei, Anhui, 230001, China
Beijing Cancer Hospital
Beijing, Beijing Municipality, 100142, China
The Second Affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing Municipality, 400010, China
Fujian Provincial Cancer Hospital
Fuzhou, Fujian, 350014, China
First Affiliated Hospital of Xiamen University
Xiamen, Fujian, 361003, China
Gansu Provincial Maternity and Child-care Hospital
Lanzhou, Gansu, 730050, China
The First Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, 510080, China
Cancer Hospital of Shantou University Medical College
Shantou, Guangdong, 515063, China
Guangxi Medical University Affiliated Tumor Hospital
Nanning, Guangxi, 530200, China
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, 150091, China
The Second Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 450014, China
Hubei Cancer Hospital
Wuhan, Hubei, 430079, China
Xiangyang Central Hospital
Xiangyang, Hubei, 441138, China
The Affiliated Hospital of Nanjing University Medical School
Nanjing, Jiangsu, 210008, China
Jiangxi Maternal and Child Health Hospital
Nanchang, Jiangxi, 330006, China
The First Hospital of Jilin University
Changchun, Jilin, 130021, China
The First Affiliated Hospital of Xian Jiaotong University
Xi'an, Shaanxi, 710061, China
Cancer Hospital of Shandong First Medical University
Jinan, Shandong, 250117, China
Affiliated Hospital of Jining Medical University
Jining, Shandong, 272029, China
Linyi Cancer Hospital
Linyi, Shandong, 276001, China
Yantai Yuhuangding Hospital
Yantai, Shandong, 264000, China
Obstetrics & Gynecology Hospital of Fudan University
Shanghai, Shanghai Municipality, 200011, China
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 200032, China
Sichuan Provincial People's Hospital
Chengdu, Sichuan, 610072, China
Tianjin Medical University Cancer Institute & Hospital
Tianjin, Tianjin Municipality, 300060, China
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, 310022, China
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang, 325015, China
Gynekologicko-porodnická klinika, Fakultni nemocnice Brno
Brno, 60200, Czechia
University Hospital Olomouc - Onkologická klinika- Fakultni
Olomouc, 77900, Czechia
Fakultní nemocnice Motol a Homolka
Prague, 15000, Czechia
Fakultní nemocnice Bulovka
Prague, 18081, Czechia
Aalborg Universit Hospital
Aalborg, 9000, Denmark
Rigshospitalet
Copenhagen, 2100, Denmark
Herlev og Gentofte Hospital
Herlev, 2730, Denmark
Odense University Hospital
Odense, 5000, Denmark
Kuopio University HPT
Kuopio, 70210, Finland
OYS Naisten poliklinikka
Oulu, 90029, Finland
ICO - Site Paul Papin
Angers, 49055, France
CHU Besançon Service Oncologie
Besançon, 25000, France
Centre François Baclesse
Caen, 14000, France
Clinique Victor Hugo - Centre Jean Bernard
Le Mans, 72000, France
Hôpital Nord Bâtiment Mistral
Marseille, 13015, France
Hôpital Saint Louis
Paris, 75010, France
ICO - Site René Gauducheau
Saint-Herblain, 44800, France
Institut de Cancérologie de Strasbourg Europe - ICANS
Strasbourg, 67000, France
Alexandra General Hospital of Athens
Athens, 11528, Greece
Aretaieio Hospital
Athens, 11528, Greece
University General Hospital Attikon
Chaïdári, 124 62, Greece
General Hospital of Kalamata
Kalamata, 24100, Greece
IASO General Clinic
Marousi, 151 23, Greece
Debreceni Egyetem
Debrecen, 4032, Hungary
Bács-Kiskun Vármegyei Oktatókórház
Kecskemét, 6000, Hungary
Lady Davis Carmel Medical Center
Haifa, 3436212, Israel
Hadassah Ein Kerem Medical Center
Jerusalem, 9112001, Israel
Rabin Medical Center-Beilinson Campus
Petah Tikva, 4941492, Israel
Sheba Medical Center
Ramat Gan, 5265601, Israel
Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari
Bari, 70124, Italy
Azienda Ospedaliera Cannizzaro - Oncologia
Catania, 95126, Italy
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST)
Meldola, 47014, Italy
Ospedale San Raffaele
Milan, 20132, Italy
Istituto Nazionale dei Tumori
Milan, 20133, Italy
Istituto Europeo di Oncologia
Milan, 20141, Italy
Humanitas San Pio X
Milan, 20159, Italy
Istituto Nazionale Tumori Fondazione G. Pascale
Naples, 80131, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Roma, 00168, Italy
Azienda Ospedaliera Ordine Mauriziano Umberto I di Torino
Torino, 10128, Italy
Radboud UMC
Nijmegen, 6525 GA, Netherlands
Erasmus Medisch Centrum
Rotterdam, 3015 AA, Netherlands
Oslo University Hospital
Oslo, 0379, Norway
Stavanger University Hospital
Stavanger, 4011, Norway
Bialostockie Centrum Onkologii im. Marii Sklodowskiej-Curie
Bialystok, 15-027, Poland
Siedleckie Centrum Onkologii
Siedlce, 08-110, Poland
Samsung Changwon Hospital
Changwon, 51353, South Korea
Keimyung Univty Dongsan Hospital
Daegu, 42601, South Korea
National Cancer Center
Goyang, 10408, South Korea
Seoul National University Bundang Hospital
Seongnam, 13620, South Korea
CHA Bundang Medical Center
Seongnam-si, 13496, South Korea
Korea University Anam Hospital
Seoul, 02841, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Severance Hospital, Yonsei University Health System
Seoul, 03722, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Gangnam Severance Hospital, Yonsei University Health System
Seoul, 06273, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, 06591, South Korea
Ewha Womans University Seoul Hospital
Seoul, 07804, South Korea
Hospital Universitari Vall, d'Hebron
Barcelona, 08035, Spain
Hospital Clinic de Barcelona
Barcelona, 08036, Spain
Hospital Universitario Reina Sofia
Córdoba, 14004, Spain
Institut Català d'Oncologia (ICO) Hospital Universitari de Girona Dr. Josep Trueta
Girona, 17007, Spain
Hospital Universitario Ramón y Cajal
Madrid, 28034, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Hospital Universitario La Paz
Madrid, 28046, Spain
Instituto Valenciano de Oncología - Valencia
Valencia, 46009, Spain
Skånes Universitetssjukhus Lund
Lund, 222 42, Sweden
Karolinska University Hospital
Stockholm, 17176, Sweden
China Medical University Hospital
Taichung, 40447, Taiwan
Taichung Veterans General Hospital
Taichung, 40705, Taiwan
Kuang Tien General Hospital
Taichung, 433004, Taiwan
National Cheng Kung University Hospital
Tainan, 70457, Taiwan
MacKay Memorial Hospital_ Taipei Branch
Taipei, 10449, Taiwan
Taipei Veterans General Hospital
Taipei, 11217, Taiwan
Baskent University Adana Application and Research Center
Adana, 01120, Turkey (Türkiye)
Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital
Ankara, 06200, Turkey (Türkiye)
Hacettepe University
Ankara, 06230, Turkey (Türkiye)
Baskent University Ankara Hospital
Ankara, 06490, Turkey (Türkiye)
Bezmialem Vakif Universitesi Tip Fakultesi Hastanesi
Istanbul, 34093, Turkey (Türkiye)
Royal Sussex County Hospital
Brighton, BN2 1ES, United Kingdom
Bristol Haematology and Oncology Centre
Bristol, BS2 8ED, United Kingdom
Addenbrooke's Hospital
Cambridge, CB2 0QQ, United Kingdom
Castle Hill Hospital
Cottingham, HU165JQ, United Kingdom
Western General Hospital
Edinburgh, EH4 2XU, United Kingdom
Royal Devon & Exeter HPT
Exeter, EX2 5DW, United Kingdom
University College London Hospitals
London, NW1 2PG, United Kingdom
Guy's Hospital
London, SE1 9RT, United Kingdom
Mount Vermont Cancer Center
Middlesex, HA6 2RN, United Kingdom
Nottingham University Hospitals NHS Trust
Nottingham, NG5 1PB, United Kingdom
Singleton Hospital
Swansea, SA2 8QA, United Kingdom
Royal Cornwall Hospital
Truro, TR1 3LJ, United Kingdom
Related Publications (1)
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.
PMID: 40966692DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
BioNTech Responsible Person
BioNTech SE
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 25, 2024
First Posted
April 1, 2024
Study Start
June 10, 2025
Primary Completion (Estimated)
March 1, 2028
Study Completion (Estimated)
November 1, 2029
Last Updated
May 20, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will not share