A Clinical Study to Investigate the Efficacy and Safety of an Investigational Combination Therapy With BNT324 and BNT327 in Patients With Advanced Lung Cancer

Phase 2RecruitingNCT06892548

BioNTech SE594 enrolled

Overview

This study aims to investigate the combination of BNT324, a B7-H3 antibody-drug conjugate (ADC) with BNT327, a programmed death-ligand 1 (PD-L1) and vascular endothelial growth factor (VEGF) bispecific antibody, in participants with advanced/metastatic or relapsed/progressive small cell lung cancer (SCLC) and non small cell lung cancer (NSCLC).

This is a two-part study designed to evaluate and establish two safe combination dose levels (recommended Phase 2 dose \[RP2D\] and a lower/another combination dose level \[RP2D-1\]) of BNT324 with BNT327 (Part 1), to determine the optimal combination dose (dose optimization \[DO\]) in NSCLC and SCLC lead indication cohorts at the RP2D and RP2D-1, to evaluate the preliminary efficacy in selected lung cancer cohorts at the highest combination dose level (in a signal seeking Part 2), and to confirm the clinical efficacy of BNT324 in combination with BNT327 at the optimal dose level in participants with advanced lung cancer in expansion cohorts (proof-of-concept \[POC\] cohorts). The study consists of a screening period, a treatment period, a safety follow-up period, and a long-term survival follow-up period. In Part 1 participants with histologically or cytologically confirmed relapsed or progressive lung cancer (both SCLC and NSCLC are eligible) will receive BNT324 in combination with BNT327 using a dose escalation design. In Part 2 of the study, BNT324 will be studied in combination with BNT327 at the RP2D compared to RP2D-1 in participants with advanced metastatic treatment-naïve NSCLC (DO Cohort 1) and relapsed/progressive SCLC after failure of cytotoxic chemotherapy with or without immuno-oncology (IO) (DO Cohort 2). The totality of the available data (e.g., safety, efficacy, pharmacokinetics etc.) will be reviewed to select the optimal dose. After the optimal dose is selected, additional participants in each cohort may be enrolled in the selected optimal dose. In the signal seeking cohorts (Cohort 3-7), participants will receive BNT324 in combination with BNT327 at the RP2D from Part 1. A predefined number of participants in Part 2 Cohort 1 and Cohort 2 will be randomized to one of the two dose levels (RP2D and RP2D-1) selected from Part 1 in a 1:1 ratio. Additional participants in Part 2 Cohort 1 and Cohort 2 may be enrolled in the selected optimal dose to further assess the efficacy and safety profile. No randomization is planned for any other cohort in Part 2 or Part 1.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Conditions

Advanced Lung Cancer

Interventions

BNT324BIOLOGICAL

Intravenous infusion

BNT327BIOLOGICAL

Intravenous infusion

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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. * Part 1: Participants with NSCLC and SCLC * Part 2 Cohort 1: Participants with NSCLC (subpopulation 1) AGA negative, 1L * Part 2 Cohort 2: Participants with SCLC, 2L+ * Part 2 Cohort 3: Participants with NSCLC (subpopulation 1) AGA negative, 2L+ * Part 2 Cohort 4: Participants with NSCLC (subpopulation 2) AGA negative, 1L * Part 2 Cohort 5: Participants with NSCLC (subpopulation 2) AGA negative, 2L+ * Part 2 Cohort 6: Participants with NSCLC AGA positive * Part 2 Cohort 7: Participants with SCLC, 1L * Have measurable disease defined by RECIST version 1.1. * Have an Eastern Cooperative Oncology Group performance status of 0 or 1. * 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. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply to all or some participants depending on the cohort.

Locations (45)

Outcomes

Primary Outcomes

Part 1 - Occurrence of dose limiting toxicities (DLTs) by dose level

Time frame: During the DLT evaluation period, i.e., the time of initiation of the first dose of investigational medicinal product (IMP) up to 21 days]

Part 1 - Occurrence of Treatment-emergent adverse events (TEAEs), serious TEAEs, treatment-related TEAEs, and treatment-related serious TEAEs by dose level

Time frame: 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

Time frame: 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 by cohort and treatment arm

Time frame: 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 by cohort and treatment arm

Time frame: 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) by cohort and treatment arm

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 1.1 based on the investigator's assessment).

Time frame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 87 months

Central Contacts

BioNTech clinical trials patient information

CONTACT

+49 6131 9084 patients@biontech.de

Data from ClinicalTrials.gov

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Precision NextGen Oncology and Research Center

Beverly Hills, California, United States

RECRUITING

Cedars Sinai Medical Center

Los Angeles, California, United States

RECRUITING

UCLA - David Geffen School of Medicine

Santa Monica, California, United States

RECRUITING

University of Iowa Hospitals & Clinics PARENT

Iowa City, Iowa, United States

RECRUITING

John Theurer Cancer Center at Hackensack UMC

Hackensack, New Jersey, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (MSKCC)

New York, New York, United States

RECRUITING

Icahn School of Medicine at Mount Sinai PRIME

New York, New York, United States

RECRUITING

Cleveland Clinic Taussig Cancer Institute Case Comprehensive Cancer Center

Cleveland, Ohio, United States

RECRUITING

Texas Oncology - DFW

Dallas, Texas, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

RECRUITING

...and 35 more locations

Secondary Outcomes

Part 1 - ORR by dose level

ORR, defined as the proportion of participants in whom a confirmed CR or PR is observed as best overall response (per RECIST version 1.1 based on the investigator's assessment).

Time frame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 87 months

Part 1 - Disease control rate (DCR) by dose level

DCR, defined as the proportion of participants with confirmed CR, PR, or stable disease (SD) as best overall response (per RECIST version 1.1 based on the investigator's assessment).

Time frame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 87 months

Part 2 all cohorts - (PFS) by cohort and treatment arm

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 version 1.1 based on the investigator's assessment.

Time frame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 87 months

Part 2 all cohorts - Duration of response (DOR) by cohort and treatment arm

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 version 1.1 based on the investigator's assessment).

Time frame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 87 months

Part 2 all cohorts - Overall survival (OS) by cohort and treatment arm

OS, defined as the time from first dose of IMP to death from any cause.

Time frame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 87 months

Part 2 all cohorts - DCR by cohort and treatment arm

DCR, defined as the proportion of participants with confirmed CR, PR, or SD as best overall response (per RECIST version 1.1 based on the investigator's assessment).

Time frame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 87 months

Part 2 all cohorts - Time to response (TTR) by cohort and treatment arm

TTR, defined as the time from first dose of IMP to first objective response (CR or PR per RECIST version 1.1 based on the investigator's assessment).

Time frame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 87 months

Part 2 cohorts 3-7 - Occurrence of TEAEs, serious TEAEs, treatment-related TEAEs, and treatment-related serious TEAEs by cohort and treatment arm

Time frame: 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 by cohort and treatment arm

Time frame: 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