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

Endometrial Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06340568
• Other study ID #: BNT323-01
• Secondary ID: GOG-31052023-507
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: April 2024
• Est. completion date: August 2028

Study information

• Verified date: March 2024
• Source: BioNTech SE
• Contact: BioNTech clinical trials patient information
• Phone: +49 6131 9084
• Email: patients[@]biontech.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical study is to assess the efficacy of BNT323/DB-1303 compared with investigator's choice of chemotherapy in terms of progression-free survival (PFS) by blinded independent central review (BICR) in the endometrial cancer population.

Description:

This is an open-label, randomized, multi-site, Phase III, interventional clinical study designed to determine the efficacy and safety of BNT323/DB-1303 compared with investigator's choice of single agent chemotherapy in previously treated patients with recurrent endometrial cancer, whose disease has progressed on at least one line of platinum-based therapy. Owing to the differences in availability of immune checkpoint inhibitors (ICIs) between countries, there will be two cohorts in the study: - Cohort 1 (main cohort): Patients that have had prior ICI treatment. - Cohort 2 (China only): Patients that have not had prior ICI treatment. In each cohort, patients will be randomized 2:1 to receive either BNT323/DB-1303 or investigator's choice of single agent chemotherapy (doxorubicin or paclitaxel) until Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 defined progressive disease (PD) unless there is unacceptable toxicity, withdrawal of consent, or another criterion for discontinuation is met.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 468
• Est. completion date: August 2028
• Est. primary completion date: October 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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,
• Is documented as HER2 1+, 2+, or 3+ score on immunohistochemistry (IHC) as determined by the Central Laboratory, 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 1.1.
• Have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Have a life expectancy of =12 weeks at screening.

Cohort 1 (main cohort) specific inclusion criteria:

• Have had at least one prior line of platinum-based therapy (in any setting) and prior ICI treatment (in any setting). Up to three lines of prior therapy are allowed. Prior hormonal therapy and radiation are allowed and do not count as prior lines of therapy. Platinum-based chemotherapy and ICI may have been given together or in separate lines of therapy.
• Note: If a patient discontinues treatment due to treatment-related toxicity (no clear progression) and starts a new anti-cancer treatment, these are counted as one line of therapy.

Cohort 2 (China only) specific inclusion criteria:

• Have had at least one prior line of platinum-based therapy (in any setting). Up to three lines of prior therapy are allowed. Prior hormonal therapy and radiation are allowed and do not count as prior lines of therapy. Only patients who have not had prior ICI treatment will be enrolled in this cohort.
• Note: If a patient discontinues treatment due to treatment related toxicity (no clear progression) and starts a new anti-cancer treatment, these are counted as one line of therapy.

Key Exclusion Criteria:

• Ineligible for all options in the investigator's choice of chemotherapy arm. Patients with contraindications to paclitaxel and doxorubicin treatment, per local prescribing information and institutional guidelines, cannot be enrolled to the study.
• Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to randomization.
• Have an uncontrolled intercurrent illness that would limit compliance with study requirement or substantially increase risk of incurring adverse events (AEs).
• Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization.
• 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.
• Patients with prior use of immunosuppressive medication within 14 days prior to 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. Patients receiving corticosteroids may continue if the dose is stable upon giving 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 study randomization, severe asthma, severe chronic obstructive pulmonary disorder, restrictive lung disease, significant pleural effusion etc.), and 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 randomization.
• Have unresolved toxicities from previous anti-cancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade =1 or baseline.
• Are pregnant or breastfeeding or are planning pregnancy during the study or within 7 months after last study treatment.
• Have a history of allergies, hypersensitivities, or intolerance to the study treatments (investigational medicinal products and auxiliary medicinal product) including any excipients thereof or to other monoclonal antibodies.
• Had prior treatment with topoisomerase I inhibitors, including Antibody-drug conjugates (ADCs) with exatecans.
• Have left ventricular ejection fraction (LVEF) <50% by either echocardiography (ECHO) or multiple-gated acquisition (MUGA) within 28 days before randomization. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Endometrial Cancer
• Endometrial Neoplasms

Intervention

Drug:
• BNT323/DB-1303
intravenous (IV) infusion
• Doxorubicin
IV bolus or infusion
• Paclitaxel
IV infusion

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
BioNTech SE	DualityBio Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PFS by BICR in the endometrial cancer population	PFS by BICR defined as the time from randomization to the first objective tumor progression (per RECIST 1.1) or death from any cause, whichever occurs first.	Up to approximately 52 months
Secondary	Overall survival (OS) in the endometrial cancer population	OS defined as the time from randomization to death from any cause.	Up to approximately 52 months
Secondary	PFS assessed by the investigator in the endometrial cancer population	PFS assessed by the investigator defined as the time from randomization to the first objective tumor progression (per RECIST 1.1) or death from any cause, whichever occurs first.	Up to approximately 52 months
Secondary	Objective response rate (ORR) in the endometrial cancer population	ORR defined as the proportion of patients in whom a complete response (CR) or partial response (PR) (per RECIST 1.1) is observed as best overall response with confirmation.	Up to approximately 52 months
Secondary	Duration of response (DoR) in the endometrial cancer population	DoR defined as the time from first objective response (CR or PR per RECIST 1.1) to first occurrence of objective tumor progression (PD per RECIST 1.1) or death from any cause, whichever occurs first.	Up to approximately 52 months
Secondary	Number of patients with occurrence of treatment-emergent adverse events (TEAEs)	TEAEs assessed according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) including Grade =3, serious, and fatal TEAEs by relationship.	Up to 35 days after the last dose of study treatment
Secondary	Number of patients with occurrence of dose reduction, delay, and discontinuation of study treatments due to TEAEs		Up to 35 days after the last dose of study treatment