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.
Eligibility
Sex
FEMALE
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Cohort 1: PFS assessed by blinded independent central review (BICR) in participants with HER2 IHC 1+/2+ recurrent endometrial cancer — Up to approximately 53 months 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.
Cohort 2: ORR assessed by BICR in participants with HER2 IHC 3+ recurrent endometrial cancer — Up to approximately 53 months Defined as the proportion of participants with a CR or PR (per RECIST v1.1) as best overall response with confirmation.
Trial sites (191)
Facility
City
Region
Status
Yale University School of Medicine
New Haven
Connecticut
Recruiting
MedStar Washington Hospital Center
Washington D.C.
District of Columbia
Recruiting
Broward Health Medical Center
Fort Lauderdale
Florida
Recruiting
OSF Saint Francis Medical Center
Peoria
Illinois
Recruiting
Carle Cancer Institute
Urbana
Illinois
Recruiting
WK Cancer Center
Shreveport
Louisiana
Recruiting
The Center of Hope Reno
Reno
Nevada
Recruiting
NYU Langone Hospital - Long Island
Mineola
New York
Recruiting
NYU Langone Health
New York
New York
Recruiting
SUNY Upstate Medical University
Syracuse
New York
Recruiting
Miami Valley Hospital South
Centerville
Ohio
Recruiting
Ohio State University
Hilliard
Ohio
Recruiting
Peggy & Charles Stephenson Oklahoma Cancer Center
Oklahoma City
Oklahoma
Recruiting
Sanford Cancer Center
Sioux Falls
South Dakota
Recruiting
Texas Oncology, P.A.
Tyler
Texas
Recruiting
Intermountain Healthcare
Murray
Utah
Recruiting
Centro de Oncologia Dr. Doreski - Fundación Respirar
Buenos Aires
Argentina
Recruiting
Centro de Investigaciones Medicas Mar del Plata
Buenos Aires
Argentina
Recruiting
Hospital Británico de Buenos Aires
Buenos Aires
Argentina
Recruiting
Investigaciones CORI S.R.L.
La Rioja
Argentina
Recruiting
Hospital Provincial del Centenario
Rosario
Argentina
Recruiting
Centro Oncológico de Excelencia
San Juan
Argentina
Recruiting
Adelaide Oncology & Haematology
Adelaide
Australia
Recruiting
Cancer Research SA
Adelaide
Australia
Recruiting
Monash Health Clinical Trial Center
Clayton
Australia
Recruiting
Gosford Hospital
Gosford
Australia
Recruiting
Peter MacCallum Cancer Centre
Melbourne
Australia
Recruiting
Frankston Hospital
Melbourne
Australia
Recruiting
Shoalhaven Cancer Care Centre
Nowra
Australia
Recruiting
Sunshine Hospital
Saint Albans
Australia
Recruiting
Mater Hospital Brisbane
South Brisbane
Australia
Recruiting
Wollongong Hospital
Wollongong
Australia
Recruiting
Institut Jules Bordet
Brussels
Belgium
Recruiting
Cliniques Universitaires Saint-Luc
Brussels
Belgium
Recruiting
Universitair Ziekenhuis Antwerpen (UZA)
Edegem
Belgium
Recruiting
Universitair Ziekenhuis Gent
Ghent
Belgium
Recruiting
AZ Groeninge VZW
Kortrijk
Belgium
Recruiting
UZ Leuven
Leuven
Belgium
Recruiting
CHU UCL Namur-Sainte-Elisabeth
Namur
Belgium
Recruiting
Fundação Sao Francisco Xavier
Ipatinga
Brazil
Recruiting
+ 151 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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