Advanced Lung Cancer
Conditions
Keywords
Small cell lung cancer (SCLC), Non-small cell lung cancer (NSCLC), Programmed death-ligand 1 (PD-L1), Vascular endothelial growth factor (VEGF), Bispecific antibody, BNT324 (DB-1311), BNT327, Combination with chemotherapy, Combination with other investigational agents, Immunotherapy, Treatment-naïve
Brief summary
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).
Detailed description
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.
Sponsors
BioNTech SE
DualityBio Inc.
Biotheus Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 - Occurrence of dose limiting toxicities (DLTs) by dose level | 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 | 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 2 cohorts 1 and 2 - Occurrence of TEAEs, serious TEAEs, treatment-related TEAEs, and treatment-related serious TEAEs by cohort and treatment arm | 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 | 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 | From the time of initiation of the first dose of IMP to end of study, i.e., up to 87 months | 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). |
| Part 2 cohorts 3-7 - ORR by cohort | From the time of initiation of the first dose of IMP to end of study, i.e., up to 87 months | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 - ORR by dose level | From the time of initiation of the first dose of IMP to end of study, i.e., up to 87 months | 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). |
| Part 1 - Disease control rate (DCR) by dose level | From the time of initiation of the first dose of IMP to end of study, i.e., up to 87 months | 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). |
| Part 2 all cohorts - (PFS) by cohort and treatment arm | From the time of initiation of the first dose of IMP to end of study, i.e., up to 87 months | 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. |
| Part 2 all cohorts - Duration of response (DOR) by cohort and treatment arm | From the time of initiation of the first dose of IMP to end of study, i.e., up to 87 months | 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). |
| Part 2 all cohorts - Overall survival (OS) by cohort and treatment arm | From the time of initiation of the first dose of IMP to end of study, i.e., up to 87 months | OS, defined as the time from first dose of IMP to death from any cause. |
| Part 2 all cohorts - DCR by cohort and treatment arm | From the time of initiation of the first dose of IMP to end of study, i.e., up to 87 months | 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). |
| Part 2 all cohorts - Time to response (TTR) by cohort and treatment arm | From the time of initiation of the first dose of IMP to end of study, i.e., up to 87 months | 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). |
| Part 2 cohorts 3-7 - Occurrence of TEAEs, serious TEAEs, treatment-related TEAEs, and treatment-related serious TEAEs by cohort and treatment arm | 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 | 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 | — |
Countries
Australia, China, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTBioNTech clinical trials patient information
STUDY_DIRECTORBioNTech Responsible Person
BioNTech SE
Outcome results
None listed