A Clinical Trial to Test if an Investigational Combination Therapy With BNT326 and BNT327 is Safe and Potentially Beneficial for People With Advanced Non-small Cell Lung Cancer (NSCLC)
- Conditions
- Non-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT07111520
- Lead Sponsor
- BioNTech SE
- Brief Summary
This is a multi-site, open-label, dose-finding study, consisting of Parts 1, 2a, and 2b to investigate the combination of BNT326 with BNT327 in participants with relapsed, progressive as well as treatment-naïve, advanced/metastatic non-small cell lung cancer (NSCLC).
This study will enroll adult participants with histologically or cytologically confirmed NSCLC that is advanced (i.e., either metastatic or recurrent tumors with no known curative treatment available).
- Detailed Description
Part 1 is a dose escalation to evaluate and establish two or three safe combination dose levels (DL1 and DL2 and optionally DL3) of BNT326 with BNT327.
Part 2a is a dose expansion to evaluate the preliminary efficacy, safety, and tolerability.
Part 2b is a dose optimization and contribution of components part.
Parts 1 and 2a (Cohort A) will enroll participants with previous exposure to therapy for advanced/metastatic disease. Part 2a (Cohort B) and Part 2b (Cohorts C and D) will enroll less heavily pre-treated participants, namely those without prior systemic treatment for advanced/metastatic disease.
The sponsor, having heard the internal review committee, may determine the dose levels for each arm in Cohorts C and D based on data generated from Parts 1 and 2a. The dose levels chosen for Cohorts C and D will not exceed the highest dose level investigated in this study.
Parts 1 and 2a will be non-randomized. In Part 2b, participants will be randomized to different treatments within each cohort.
The study consists of a screening period, a treatment period, a safety follow-up period, an efficacy follow-up period, and a long-term survival follow-up. Participants will receive study treatment until disease progression, withdrawal of consent, termination of the study by the sponsor, unacceptable toxicity, or for a maximum duration of 24 months (or for the maximum duration as per the local product label for participants receiving standard of care \[SoC\] therapy), whichever occurs first. For each study participant, the treatment and follow-up periods are projected to be completed within \~36 months, unless participants are continuing to benefit from treatment per investigator's recommendation and upon sponsor approval.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 420
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1 - BNT326 (DL1, starting dose) + BNT327 BNT326 Combination therapy of BNT326 and BNT327. In participants with second-line (or higher) 2L(+), squamous or non-squamous NSCLC, actionable genomic alterations (AGA)-negative/positive, any PD-L1. Part 1 - BNT326 (DL1, starting dose) + BNT327 BNT327 Combination therapy of BNT326 and BNT327. In participants with second-line (or higher) 2L(+), squamous or non-squamous NSCLC, actionable genomic alterations (AGA)-negative/positive, any PD-L1. Part 1 - BNT326 (DL2) + BNT327 BNT326 Combination therapy of BNT326 and BNT327. In participants with 2L(+), squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1. Part 1 - BNT326 (DL2) + BNT327 BNT327 Combination therapy of BNT326 and BNT327. In participants with 2L(+), squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1. Part 1 - BNT326 (DL3, optional) + BNT327 BNT326 Combination therapy of BNT326 and BNT327. In participants with 2L(+), squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1. Part 1 - BNT326 (DL3, optional) + BNT327 BNT327 Combination therapy of BNT326 and BNT327. In participants with 2L(+), squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1. Part 2a (Cohort A, Arm 1) - BNT326 (DL1) + BNT327 BNT326 Combination therapy of BNT326 and BNT327. In participants with 2L+ squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1. Part 2a (Cohort A, Arm 1) - BNT326 (DL1) + BNT327 BNT327 Combination therapy of BNT326 and BNT327. In participants with 2L+ squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1. Part 2a (Cohort A, Arm 2) - BNT326 (DL2) + BNT327 BNT326 Combination therapy of BNT326 and BNT327. In participants with 2L+ squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1. Part 2a (Cohort A, Arm 2) - BNT326 (DL2) + BNT327 BNT327 Combination therapy of BNT326 and BNT327. In participants with 2L+ squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1. Part 2a (Cohort B, Arm 1) - BNT326 (DL1) + BNT327 BNT326 Combination therapy of BNT326 and BNT327. In participants with first-line (1L) squamous or non-squamous NSCLC, AGA-negative, any PD-L1. Part 2a (Cohort B, Arm 1) - BNT326 (DL1) + BNT327 BNT327 Combination therapy of BNT326 and BNT327. In participants with first-line (1L) squamous or non-squamous NSCLC, AGA-negative, any PD-L1. Part 2a (Cohort B, Arm 2) - BNT326 (DL2) + BNT327 BNT326 Combination therapy of BNT326 and BNT327. In participants with 1L squamous or non-squamous NSCLC, AGA-negative, any PD-L1. Part 2a (Cohort B, Arm 2) - BNT326 (DL2) + BNT327 BNT327 Combination therapy of BNT326 and BNT327. In participants with 1L squamous or non-squamous NSCLC, AGA-negative, any PD-L1. Part 2b (Cohort C, Arm 1) - BNT326 (DL1) + BNT327 BNT326 Combination therapy of BNT326 and BNT327. In participants with 2L+, squamous or non-squamous NSCLC, AGA-negative or epithelial growth factor receptor (EGFR) activating mutation, any PD-L1. Part 2b (Cohort C, Arm 1) - BNT326 (DL1) + BNT327 BNT327 Combination therapy of BNT326 and BNT327. In participants with 2L+, squamous or non-squamous NSCLC, AGA-negative or epithelial growth factor receptor (EGFR) activating mutation, any PD-L1. Part 2b (Cohort C, Arm 2) - BNT326 (DL2) + BNT327 BNT326 Combination therapy of BNT326 and BNT327. In participants with 2L+, squamous or non-squamous NSCLC, AGA-negative or EGFR activating mutation, any PD-L1. Part 2b (Cohort C, Arm 2) - BNT326 (DL2) + BNT327 BNT327 Combination therapy of BNT326 and BNT327. In participants with 2L+, squamous or non-squamous NSCLC, AGA-negative or EGFR activating mutation, any PD-L1. Part 2b (Cohort C, Arm 3) - BNT326 monotherapy BNT326 BNT326 monotherapy (DL2). In participants with 2L+, squamous or non-squamous NSCLC, AGA-negative or EGFR activating mutation, any PD-L1. Part 2b (Cohort D1, Arm 1) - BNT326 (DL2) + BNT327 BNT326 Combination therapy of BNT326 and BNT327. In participants with 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 ≥50%. Part 2b (Cohort D1, Arm 1) - BNT326 (DL2) + BNT327 BNT327 Combination therapy of BNT326 and BNT327. In participants with 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 ≥50%. Part 2b (Cohort D1, Arm 2) - Pembrolizumab Pembrolizumab Pembrolizumab monotherapy. In participants with 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 ≥50%. Part 2b (Cohort D1, Arm 3) - BNT327 monotherapy BNT327 BNT327 monotherapy. In participants with 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 ≥50%. Part 2b (Cohort D2, Arm 1) - BNT326 (DL2) + BNT327 BNT326 Combination therapy of BNT326 and BNT327. In participants with 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 \<50%. Part 2b (Cohort D2, Arm 1) - BNT326 (DL2) + BNT327 BNT327 Combination therapy of BNT326 and BNT327. In participants with 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 \<50%. Part 2b (Cohort D2, Arm 2) - SoC - Pembrolizumab + chemotherapy Pembrolizumab Combination therapy of pembrolizumab and chemotherapy. In participants with 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 \<50%. Part 2b (Cohort D2, Arm 2) - SoC - Pembrolizumab + chemotherapy SoC Combination therapy of pembrolizumab and chemotherapy. In participants with 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 \<50%.
- Primary Outcome Measures
Name Time Method Part 1 - Occurrence of dose limiting toxicities (DLTs) within a participant 21 days starting on Day 1 of Cycle 1 During the DLT evaluation period by dose level
Part 1 and Part 2a - Occurrence of treatment emergent adverse events (TEAEs), treatment-related adverse events (TRAE), treatment emergent serious adverse events (TESAE), treatment-related serious adverse events (TRSAE) from the first dose of investigational medicinal product (IMP) up to 90 days after the last dose of IMP or until a new systemic anti-cancer therapy is started, whichever occurs first (up to a maximum of 27 months) Part 1 and Part 2a - Occurrence of dose interruption, reduction, and discontinuation due to TEAEs from the first dose of IMP up to 90 days after the last dose of IMP or until a new systemic anti-cancer therapy is started, whichever occurs first (up to a maximum of 27 months) Part 2a and Part 2b - Objective response rate (ORR) from the time of initiation of the first dose of IMP to approximately 36 months Defined as the percentage of participants in whom a confirmed complete response (CR) or partial response (PR) (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\] based on the investigator's assessment) is observed as best overall response.
- Secondary Outcome Measures
Name Time Method Part 1 - ORR from the time of initiation of the first dose of IMP to approximately 36 months Defined as the percentage of participants in whom a confirmed CR or PR (per RECIST v1.1 based on the investigator's assessment) is observed as best overall response.
Part 2b - Occurrence of TEAEs, TRAEs, TESAEs, TRSAEs from the first dose of IMP up to 90 days after the last dose of IMP or until a new systemic anti-cancer therapy is started, whichever occurs first (up to a maximum of 27 months) Part 2b - Occurrence of dose interruption, reduction, and discontinuation due to TEAEs from the first dose of IMP up to 90 days after the last dose of IMP or until a new systemic anti-cancer therapy is started, whichever occurs first (up to a maximum of 27 months) Part 2a and Part 2b - Progression free survival based on the investigator's assessment from the first dose of IMP to approximately 36 months Defined as the time from first dose of IMP to the first objective tumor progression (progressive disease \[PD\] per RECIST v1.1) or death from any cause, whichever occurs first.
Part 2a and Part 2b - Disease control rate from the first dose of IMP to approximately 36 months Defined as the proportion of participants with CR, PR, or stable disease (per RECIST v1.1 based on the investigator's assessment) as best overall response.
Part 2a and Part 2b - Duration of response from the first dose of IMP to approximately 36 months Defined as the time from first confirmed objective response (CR or PR per RECIST v1.1 based on the investigator's assessment) to first occurrence of objective tumor progression (PD per RECIST v1.1 based on the investigator's assessment) or death from any cause, whichever occurs first
Part 2a and Part 2b - Time to response from the first dose of IMP to approximately 36 months Defined as the time from first dose of IMP to first confirmed objective response (CR or PR per RECIST v1.1 based on the investigator's assessment) in participants with a confirmed objective response
Part 2a and Part 2b - Overall survival from the first dose of IMP to approximately 36 months Defined as the time from first dose of IMP to death from any cause
All cohorts - PK assessment: Maximum concentration derived from serum concentrations of BNT326 ADC, total anti-HER3 antibody component, and unconjugated payload from the first IMP up to safety follow-up, approximately 90 days post last IMP dose For applicable participants, if data permits.
All cohorts - PK assessment: Time to reach maximum (peak) serum concentration derived from serum concentrations of BNT326 ADC, total anti-HER3 antibody component, and unconjugated payload from the first dose of IMP up to safety follow-up, approximately 90 days post last IMP dose For applicable participants, if data permits.
All cohorts - Anti-drug antibody (ADA) prevalence and ADA incidence up to 1 year from the last dose of IMP By cohort and combination treatment regimen for applicable participants