BNT151 as a Monotherapy and in Combination With Other Anti-cancer Agents in Patients With Solid Tumors
- Registration Number
- NCT04455620
- Lead Sponsor
- BioNTech SE
- Brief Summary
This was an open-label, multicenter Phase I/IIa dose escalation, safety, pharmacokinetic and pharmacodynamic (PD) study of BNT151 with expansion cohorts in various solid tumor indications.
The study was planned to be performed in Part 1, Part 2A, and Part 2B with adaptive design elements. Part 2 was not conducted because of the clinical study being terminated early.
The monotherapy dose escalation, (Part 1) of this clinical study enrolled participants with various solid tumors that are metastatic or of advanced unresectable stage for whom there was no available standard therapy likely to confer clinical benefit, or participants who are not candidates for such available therapy. Dose escalation followed an accelerated titration design, i.e., started with single participant cohorts followed by larger participant cohorts informed by the 3+3 design.
Part 1 of the study also planed to implement a dedicated biomarker cohort in BNT151 monotherapy. The biomarker cohort was planned to recruit participants at selected sites in the United States (US) only. The objective of the cohort was to observe PD activity and drug-induced changes in the blood and tumor and only to generate data for exploratory endpoints or additional research. However, the biomarker cohort was not opened, and therefore no data were generated.
During combination dose escalation (Part 2A), participants with squamous cell carcinoma of head and neck, and hepatocellular carcinoma were planned to be enrolled and treated with a combination of BNT151 and pembrolizumab. Once Part 2A was completed, participants with renal cell carcinoma, non-small cell lung cancer, and triple negative breast cancer were planned to be enrolled (Part 2B) and treated with a combination of BNT151 with the respective standard of care (SoC).
- Detailed Description
The study was terminated early due to sponsor's decision after careful considerations including recruitment projections and available data, and not due to any safety concerns. At the time of the termination, fewer dose levels were tested than anticipated.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 49
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1: BNT151 BNT151 Monotherapy dose escalation in participants with advanced solid malignancies until the MTD and/or RP2D
- Primary Outcome Measures
Name Time Method Number of Participants With Dose Limiting Toxicities (DLTs) During the DLT Evaluation Period in Part 1 From first dose of IMP up to 21 days (Cycle 1). Number of Paticipants With at Least One TEAE Leading to Dose Reduction, Dose Interruption, and Treatment Discontinuation of BNT151 From first dose of IMP through treatment completion, a maximum of 24 months. A TEAE was defined as any AE with an onset date on or after the first administration of IMP (if the AE was absent before the first administration of IMP) or worsened after the first administration of IMP (if the AE was present before the first administration of IMP). AEs with an onset date more than 60 days after the last administration of IMP were considered as treatment emergent only if assessed as related to IMP by the investigator.
Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) Including Grade ≥3, Serious, Fatal TEAE by Relationship From first dose of IMP through study completion, a maximum of 30 months. A TEAE was defined as any adverse event (AE) with an onset date on or after the first administration of IMP (if the AE was absent before the first administration of IMP) or worsened after the first administration of IMP (if the AE was present before the first administration of IMP). AEs with an onset date more than 60 days after the last administration of IMP were considered as treatment emergent only if assessed as related to IMP by the investigator.
The intensity of an TEAE was graded according to the NCI CTCAE version 5.0. Grade 3=Severe, Grade 4=Life threatening, Grade 5=Death.
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) Through study completion, a maximum of 30 months. ORR was defined as the proportion of participants in whom a complete response (CR) or partial response (PR) (per RECIST version 1.1) was observed as best overall response.
Confirmed ORR was defined as the proportion of participants in whom a CR or PR (per RECIST version 1.1) was observed as best overall response and has been confirmed with a subsequent assessment of objective response at least 4 weeks apart.Duration of Response (DOR) Through study completion, a maximum of 30 months. DOR was defined as the time from first objective response (CR or PR per RECIST version 1.1) to first occurrence of objective tumor progression (progressive disease per RECIST version 1.1) or death from any cause, whichever occurred first.
Reporting groups with zero participants with confirmed objective response are not included.Disease Control Rate (DCR) Through study completion, a maximum of 30 months. DCR was defined as the proportion of participants in whom a CR or PR or stable disease (SD) (per RECIST version 1.1, SD assessed at least 6 weeks after first dose) was observed as best overall response.
Trial Locations
- Locations (6)
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Sarah Cannon Research Institute at Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
NEXT Oncology
🇺🇸San Antonio, Texas, United States
Vall d´Hebron Institute of Oncology (VHIO)
🇪🇸Barcelona, Spain
START Madrid - HM CIOCC
🇪🇸Madrid, Spain
Yale Cancer Center🇺🇸New Haven, Connecticut, United States