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
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.
Arms & interventions
- DrugBNT323/DB-1303
intravenous (IV) infusion
- DrugDoxorubicin
IV bolus or infusion
- DrugPaclitaxel
IV infusion
- DrugDocetaxel
IV infusion
Outcome measures
Primary
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.
Time frame: 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.
Time frame: Up to approximately 53 months
Secondary
Cohort 1: Overall survival (OS) in participants with HER2 IHC 1+/2+ recurrent endometrial cancer
Time frame: Up to approximately 53 months
Cohort 1: PFS assessed by the investigator in participants with HER2 IHC 1+/2+ recurrent endometrial cancer
Time frame: Up to approximately 53 months
Cohort 1: ORR assessed by BICR in participants with HER2 IHC 1+/2+ recurrent endometrial cancer
Time frame: Up to approximately 53 months
Cohort 1: ORR assessed by the investigator in participants with HER2 IHC 1+/2+ recurrent endometrial cancer
Time frame: Up to approximately 53 months
Cohort 1: Duration of response (DoR) assessed by BICR in participants with HER2 IHC 1+/2+ recurrent endometrial cancer
Time frame: Up to approximately 53 months
Cohort 1: DoR assessed by the investigator in participants with HER2 IHC 1+/2+ recurrent endometrial cancer
Time frame: 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)
Time frame: 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.
Time frame: 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
Time frame: Up to approximately 53 months
Cohort 2: DoR assessed by BICR in participants with HER2 IHC 3+ recurrent endometrial cancer
Time frame: Up to approximately 53 months
Cohort 2: DoR assessed by the investigator in participants with HER2 IHC 3+ recurrent endometrial cancer
Time frame: Up to approximately 53 months
Cohort 2: PFS assessed by BICR in participants with HER2 IHC 3+ recurrent endometrial cancer
Time frame: Up to approximately 53 months
Cohort 2: PFS assessed by the investigator in participants with HER2 IHC 3+ recurrent endometrial cancer
Time frame: Up to approximately 53 months
Cohort 2: OS in participants with HER2 IHC 3+ recurrent endometrial cancer
Time frame: Up to approximately 53 months
Cohort 2: Percentage of participants with HER2 IHC 3+ recurrent endometrial cancer with occurrence of TEAEs
Time frame: 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.
Time frame: Up to 35 days after the last dose of study treatment
Eligibility criteria
Study locations (7)
MedStar Washington Hospital Center
Washington D.C., District of Columbia, 20010
Broward Health Medical Center
Fort Lauderdale, Florida, 33316
The Center of Hope Reno
Reno, Nevada, 89511
NYU Langone Health
New York, New York, 10016
Miami Valley Hospital South
Centerville, Ohio, 45459
Ohio State University
Hilliard, Ohio, 43026
Sanford Cancer Center
Sioux Falls, South Dakota, 57104
References
- 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.(PubMed)