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NCT06340568PHASE3Recruiting

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

BioNTech SE

Start Date

6/10/2025

Completion Date

11/1/2029

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.

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

BNT323/DB-1303

DRUG

Doxorubicin

DRUG

Paclitaxel

DRUG

Docetaxel

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Conditions

Endometrial Cancer

Locations

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 Hospital - Long Island

Mineola, New York 11501

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 Ostrava

Ostrava, 01790

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

Turun yliopistollinen keskussairaala

Turku, 20521

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 Universitaria Policlinico Sant'Orsola Malpighi IRCCS

Bologna, 40138

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

National Cancer Centre Singapore

Singapore, 168583

Singapore

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

Hospital Universitar Donostia

Donostia / San Sebastian, 20014

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)

İzmir City Hospital

Bayraklı, 35540

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