A Clinical Trial to Test if the Investigational Drug BNT329 is Safe and Potentially Beneficial for People With Advanced Solid Tumors Known to Express the Tumor Marker CA19-9
- Conditions
- Advanced Solid Cancers
- Interventions
- Drug: BNT329Drug: CA19-9-targeting monoclonal antibody
- Registration Number
- NCT07186842
- Lead Sponsor
- BioNTech SE
- Brief Summary
The main goal of this study is to evaluate the safety of BNT329 and to identify the best dose of BNT329. This will be done by measuring the number of side effects that participants experience and how severe they are.
The second goal of this study is to evaluate how well BNT329 works. This will be done by measuring the number of participants who respond to the treatment. The length of time where the tumor does not grow or spread will also be measured.
The study will also evaluate how BNT329 moves into, through, and out of the body and how the treatment affects the body.
- Detailed Description
The study will consist of up to four parts (Parts A, B, C, and D).
Parts A, B, and C will be a dose escalation to investigate the safety and tolerability of BNT329. Parts A, B, and C will enroll participants with the following advanced solid tumors known to express carbohydrate antigen 19-9 (CA19-9): pancreatic ductal adenocarcinoma (PDAC) (the most common type of pancreatic cancer), bile duct cancer, a certain type of bladder cancer that started in the lining of the bladder or urinary tract (invasive urothelial carcinoma of the bladder and urinary tract), colorectal cancer, gastroesophageal junction cancer, endometrial cancer, or ovarian cancer. The cancer must not have responded well to previous treatments.
The study will start with recruitment into Part A. Part B (testing a more frequent dosing schedule) and Part C (testing pre-dosing with a CA19-9 targeting monoclonal antibody prior to BNT329 administration) will only be opened if indicated by cumulative data from the study.
Part D will be a dose optimization and proof-of-concept study to further investigate the safety and tolerability of BNT329 and to investigate preliminary anti-tumor activity. Part D will enroll participants with second-line plus PDAC.
Parts A, B, and C will be non-randomized. In Part D, participants will be randomized (1:1) into one of two arms which will evaluate two dose levels (as selected from Parts A, B, and C).
The study consists of a screening period, a treatment period, an End of Treatment Visit, two Safety Follow-Up Visits, and a survival follow-up period. The treatment period will last for a maximum of 2 years. Participants will remain in the survival follow-up until death, withdrawal of participant's consent, or termination of the study, whichever occurs first.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 245
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation - Part A BNT329 BNT329 administered once every 3 weeks at protocol-defined dose levels Dose Escalation - Part B BNT329 BNT329 administered once every 2 weeks at protocol-defined dose levels Dose Escalation: Part C BNT329 BNT329 administered after pre-dosing with a CA19-9 targeting monoclonal antibody Dose Escalation: Part C CA19-9-targeting monoclonal antibody BNT329 administered after pre-dosing with a CA19-9 targeting monoclonal antibody Dose Expansion - Part D BNT329 Participants will be randomized to one of two arms evaluating two different doses as selected from Parts A, B, and C
- Primary Outcome Measures
Name Time Method Parts A, B, and C - Occurrence of dose-limiting toxicities within a participant First 21 days (Part A) or 28 days (Part B) after the first dose of BNT329. Per dose level/cohort.
All parts - Occurrence of treatment-emergent adverse events (TEAEs), Grade ≥3 TEAEs, serious adverse events (SAEs), treatment-related TEAEs, treatment-related Grade ≥3 TEAEs, and treatment-related SAEs From first dose of BNT329 until 60 days after the last dose of BNT329 (up to 26 months). Per dose level/cohort/arm.
All parts - Occurrence of dose interruptions, reductions, and discontinuation of BNT329 due to TEAEs From the time of initiation of the first dose of BNT329 until 60 days after the last dose of BNT329 (up to 26 months). Per dose level/cohort/arm.
Part D - Objective response rate (ORR) From first dose of BNT329 until end of study (up to approximately 36 months). Per dose level/arm. Defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) (based on the investigator's assessment) is observed as best overall response.
- Secondary Outcome Measures
Name Time Method All parts - Assessment of area under the curve derived from serum concentrations of CA19-9-unbound ADC, CA19-9-unbound total anti-CA19-9 antibody, and unconjugated YL0010014 payload First 21 days (Part A) or 28 days (Part B) after the first dose of BNT329. Per dose level/cohort/arm (if data permit)
All parts - Assessment of maximum concentration derived from serum concentrations of CA19-9-unbound ADC, CA19-9-unbound total anti-CA19 antibody, and unconjugated YL0010014 payload First 21 days (Part A) or 28 days (Part B) after the first dose of BNT329. Per dose level/cohort/arm (if data permit).
All parts - Assessment of time to reach maximum concentration derived from serum concentrations of CA19-9-unbound ADC, CA19-9-unbound total anti-CA19-9 antibody, and unconjugated YL0010014 payload First 21 days (Part A) or 28 days (Part B) after the first dose of BNT329. Per dose level/cohort/arm (if data permit).
All parts - Assessment of terminal half-life derived from serum concentrations of CA19-9-unbound ADC, CA19-9-unbound total anti-CA19-9 antibody, and unconjugated YL0010014 payload First 21 days (Part A) or 28 days (Part B) after the first dose of BNT329. Per dose level/cohort/arm (if data permit).
Parts A, B, and C - ORR From first dose of BNT329 until end of study (up to approximately 36 months). Per dose level/cohort. Defined as the proportion of participants in whom a confirmed CR or PR (based on the investigator's assessment) is observed as best overall response.
All parts - Disease control rate From first dose of BNT329 until end of study (up to approximately 36 months). Per dose level/cohort/arm. Defined as the proportion of participants in whom a CR or PR or stable disease (assessed at least 6 weeks \[±2 days\] after the first BNT329 dose) is observed as best ORR per investigator's assessment.
All parts - Duration of response From first dose of BNT329 until end of study (up to approximately 36 months). Per dose level/cohort/arm. Defined as the time from first objective response (CR or PR) to first occurrence of objective tumor progression (PD) or death from any cause, whichever occurs first.
All parts: Anti-drug antibody (ADA) prevalence From first dose of BNT329 until up to 60 days after the last dose of BNT329 (up to 26 months). Per dose level/cohort/arm. Defined as the proportion of participants who are ADA positive at any timepoint (either baseline or post-baseline) (if data permit).
All parts - ADA incidence From first dose of BNT329 until up to 60 days after the last dose of BNT329 (up to 26 months). Per dose level/cohort/arm. Defined as the proportion of participants having treatment-emergent ADA (if data permit).