A Phase Ib/II, multi-site, open-label, two-part trial to evaluate the efficacy, safety, pharmacokinetics, and recommended combination dose of BNT324 with BNT327 in participants with advanced lung cancer
Overview
- Phase
- Phase 1/2
- Status
- Not yet recruiting
- Sponsor
- BioNTech SE
- Enrollment
- 26
- Locations
- 6
- Primary Endpoint
- Part 1 - Occurrence of dose limiting toxicities (DLTs) during the DLT evaluation period
Overview
Brief Summary
Part 1 (Dose Escalation): To determine the recommended phase II dose (RP2D) of BNT324 in combination with BNT327 by assessing the safety and tolerability in participants with advanced lung cancer. Part 2 (Dose Optimization/Signal Seeking): Lead indications Cohort 1 and Cohort 2: To determine the optimal dose of BNT324 in combination with BNT327 by assessing the safety profile and efficacy of the combination therapy in the randomized dose optimization cohorts in the lead cohorts (Cohort 1 treatment naive non-sq non-small cell lung cancer (NSCLC) and Cohort 2 relapsed/progressive small cell lung cancer (SCLC)). Efficacy signal seeking cohorts 3-7: To evaluate the efficacy of BNT324 in combination with BNT327 according to response evaluation criteria in solid tumors (RECIST) v1.1.
Eligibility Criteria
- Ages
- 18 years to 65+ years (65+ Years, 18-64 Years)
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Aged ≥18 years at the time of giving informed consent.
- •Histological or cytological confirmed unresectable advanced/metastatic lung cancer. Histological classification may be based on tumor samples prior to metastatic disease. Participants with mixed histology must be classified based on the main component. Participants with NSCLC are eligible with any or no PD-L1 expression. Participants with AGA-positive disease must have received targeted therapy prior to enrollment in this study.
- •Have measurable disease defined by RECIST version 1.
- •Have an Eastern Cooperative Oncology Group performance status of 0 or
- •Have a life expectancy of ≥12 weeks.
Exclusion Criteria
- •Prior treatment with B7-H3 targeted therapy.
- •Prior treatment with ADC with topoisomerase inhibitor (e.g., datopotamab deruxtecan, trastuzumab deruxtecan). Note: This exclusion applies to participants in the first-line/treatment-naïve cohorts in the advanced/metastatic setting. Prior treatment with ADC with topoisomerase inhibitor payload is only allowed for participants in the second-line plus cohorts in the advanced/metastatic setting.
- •Is a candidate to locoregional treatment (including surgical resection, stereotactic radiotherapy or tumor ablation) with potential to induce complete or near complete response and prolonged tumor control (sometimes described as “radical” intent), per investigator’s assessment.
- •Has a history of significant hematologic toxicity to prior lines of therapy, as assessed by investigator, e.g., Grade 4 febrile neutropenia or recurrent/persistent Grade 3 to 4 neutropenia.
Outcomes
Primary Outcomes
Part 1 - Occurrence of dose limiting toxicities (DLTs) during the DLT evaluation period
Part 1 - Occurrence of dose limiting toxicities (DLTs) during the DLT evaluation period
Part 1 - Occurrence of Treatment-emergent adverse events (TEAEs), serious TEAEs, treatment-related TEAEs, and treatment-related serious TEAEs from the time of the first dose of IMP to 90 days after the last IMP dose or until new anticancer therapy is started, whichever occurs first
Part 1 - Occurrence of Treatment-emergent adverse events (TEAEs), serious TEAEs, treatment-related TEAEs, and treatment-related serious TEAEs from the time of the first dose of IMP to 90 days after the last IMP dose or until new anticancer therapy is started, whichever occurs first
Part 1 - Occurrence of dose interruption, reduction, and treatment discontinuations due to TEAEs by dose level from the time of the first dose of IMP to 90 days after the last dose of IMP or until new anticancer therapy is started, whichever occurs first
Part 1 - Occurrence of dose interruption, reduction, and treatment discontinuations due to TEAEs by dose level from the time of the first dose of IMP to 90 days after the last dose of IMP or until new anticancer therapy is started, whichever occurs first
Part 2 cohorts 1 and 2 - Occurrence of TEAEs, serious TEAEs, treatment-related TEAEs, and treatment-related serious TEAEs from the time of the first dose of IMP to 90 days after the last IMP dose or until new anticancer therapy is started, whichever occurs first
Part 2 cohorts 1 and 2 - Occurrence of TEAEs, serious TEAEs, treatment-related TEAEs, and treatment-related serious TEAEs from the time of the first dose of IMP to 90 days after the last IMP dose or until new anticancer therapy is started, whichever occurs first
Part 2 cohorts 1 and 2 - Occurrence of dose interruption, reduction, and treatment discontinuation due to TEAEs from the time of the first dose of IMP to 90 days after the last IMP dose or until new anticancer therapy is started, whichever occurs first
Part 2 cohorts 1 and 2 - Occurrence of dose interruption, reduction, and treatment discontinuation due to TEAEs from the time of the first dose of IMP to 90 days after the last IMP dose or until new anticancer therapy is started, whichever occurs first
Part 2 cohorts 1 and 2 - Objective response rate (ORR) defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) is observed as best overall response (per response evaluation criteria in solid tumors [RECIST] version v1.1 based on the investigator’s assessment).
Part 2 cohorts 1 and 2 - Objective response rate (ORR) defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) is observed as best overall response (per response evaluation criteria in solid tumors [RECIST] version v1.1 based on the investigator’s assessment).
Part 2 cohorts 3-7 - ORR defined as the proportion of participants in whom a confirmed CR or PR is observed as best overall response (per RECIST version v1.1 based on the investigator’s assessment).
Part 2 cohorts 3-7 - ORR defined as the proportion of participants in whom a confirmed CR or PR is observed as best overall response (per RECIST version v1.1 based on the investigator’s assessment).
Secondary Outcomes
- Part 1 - Disease control rate (DCR), defined as the proportion of participants with confirmed CR, PR, or stable disease (SD) as best overall response (per RECIST version v1.1 based on the investigator’s assessment).
- Part 2 all cohorts - PFS defined as the time from first dose of IMP to the first objective tumor progression (PD) or death from any cause, whichever occurs first, per RECIST v1.1 based on the investigator’s assessment.
- Part 2 all cohorts - Duration of response (DOR), 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 (per RECIST v1.1 based on the investigator’s assessment).
- Part 2 all cohorts - Overall survival (OS), defined as the time from first dose of IMP to death from any cause.
- Part 2 all cohorts - DCR, defined as the proportion of participants with confirmed CR, PR, or SD as best overall response (per RECIST v1.1 based on the investigator’s assessment).
- Part 2 all cohorts - Time to response (TTR), defined as the time from first dose of IMP to first objective response (CR or PR per RECIST v1.1 based on the investigator’s assessment)
- Part 2 cohorts 3-7 - Occurrence of TEAEs, serious TEAEs, treatment-related TEAEs, and treatment-related serious TEAEs from the time of the first dose of IMPs to 90 days after the last IMP dose or until new anticancer therapy is started, whichever occurs first.
- Part 2 cohorts 3-7 - Occurrence of dose interruption, reduction, and treatment discontinuation due to TEAEs from the time of the first dose of IMP to 90 days after the last IMP dose or until new anticancer therapy is started, whichever occurs first
- Part 1 - ORR defined as the proportion of participants in whom a confirmed CR or PR is observed as best overall response (per RECIST version v1.1 based on the investigator’s assessment).
Investigators
Clinical Trial Information Desk
Scientific
BioNTech SE