Clinical trial NCT06340568: A Clinical Study of the Anti-cancer Effects of an Investigational Therapy or Chemotherapy in Patients With Recurring Uterine Cancer
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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Endometrial Cancer
Keywords: Human epidermal growth factor receptor 2 (HER2)
HER2-expressing tumors
Recurrent endometrial cancer
IHC scores 1+, 2+, and 3+
Immune checkpoint inhibitor
Platinum-based therapy
HER2 protein expression
HER2-expressing endometrial cancer
ErbB-2 receptor
Antibody drug conjugate (ADC)
Lead sponsor: BioNTech SE
Sponsor class: INDUSTRY
Collaborators: name: DualityBio Inc.
First posted: 2024-04-01
Enrollment: 504
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 with prior immune checkpoint inhibitor (ICI) treatment.

Detailed 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 participants with recurrent endometrial cancer, whose disease has progressed on at least one line of platinum-based therapy.

Participants 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 version 1.1 (RECIST 1.1) defined progressive disease (PD) unless there is unacceptable toxicity, withdrawal of consent, or another criterion for discontinuation is met. Randomization will be stratified by HER2 expression (immunohistochemistry score 1+ vs 2+ vs 3+), number of prior lines of therapy (1 vs 2+), and prior ICI treatment (yes vs no).

The study consists of a two-part screening period (Part 1 \[tissue screening\] and Part 2 \[screening\]) 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 55 months.

Eligibility criteria: 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+, or 3+ as determined by central laboratory testing for HER2 protein 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 1.1.
* Have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
* 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. Platinum-based chemotherapy and ICI may have been given together or in separate lines of therapy.
* Have a life expectancy of ≥12 weeks at screening.

Key Exclusion Criteria:

* Ineligible for all options in the investigator's choice of chemotherapy arm. Participants 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.
* Participants 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. Participants 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, pulmonary fibrosis, radiation pneumonitis, 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 the last dose of 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 ADCs with exatecans.
* Have left ventricular ejection fraction (LVEF) \<55% by either echocardiography (ECHO) or multiple-gated acquisition (MUGA) within 28 days before randomization. This includes participants with tissue doppler E/e' ratio \>15.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: PFS assessed by BICR in the endometrial cancer population in participants with prior ICI treatment
timeFrame: Up to approximately 32 months
Secondary outcomes:
measure: PFS assessed by BICR in the endometrial cancer population in all participants with HER2-expressing recurrent endometrial cancer
timeFrame: Up to approximately 32 months
measure: Overall survival (OS) in the endometrial cancer population in participants with prior ICI treatment and in all participants
timeFrame: Up to approximately 55 months
measure: PFS assessed by the investigator in the endometrial cancer population in participants with prior ICI treatment and in all participants
timeFrame: Up to approximately 32 months
measure: Objective response rate (ORR) assessed by BICR in the endometrial cancer population in participants with prior ICI treatment and in all participants
timeFrame: Up to approximately 55 months
measure: ORR assessed by the investigator in the endometrial cancer population in participants with prior ICI treatment and in all participants
timeFrame: Up to approximately 55 months
measure: Duration of response (DoR) assessed by BICR in the endometrial cancer population in participants with prior ICI treatment and in all participants
timeFrame: Up to approximately 55 months
measure: DoR assessed by the investigator in the endometrial cancer population in participants with prior ICI treatment and in all participants
timeFrame: Up to approximately 55 months
measure: Percentage of participants with occurrence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 35 days after the last dose of study treatment
measure: Percentage of participants with occurrence of TEAEs leading to drug interruption, dose reduction, or discontinuation of study treatment.
timeFrame: Up to 35 days after the last dose of study treatment
Other outcomes:
Locations:
Study officials:
affiliation: BioNTech SE
name: BioNTech Responsible Person
role: STUDY_DIRECTOR
References: