Phase Ib/II Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of BNT324 in Combination with BNT327 in Participants with Advanced Lung Cancer
- Trial ID
- 2024-520238-31-01
- Protocol
- BNT324-01
- Sponsor
- BioNTech SE
Trial statistics
Objectives
The primary objective of this study is to determine the recommended phase II dose (RP2D) of BNT324 in combination with BNT327 by assessing safety and tolerability in participants with advanced lung cancer. Additionally, the study aims to identify the optimal dose through evaluation of the safety profile and efficacy in specific cohorts, including treatment-naive non-squamous non-small cell lung cancer (NSCLC) and relapsed or progressive small cell lung cancer (SCLC) 5. The secondary objectives include:
- Evaluation of efficacy according to RECIST v1.1 5.
- Assessment of efficacy other than objective response rate (ORR) in dose optimization and signal-seeking cohorts 5.
- Evaluation of safety in signal-seeking cohorts 4.
Participants
This clinical trial involves a total of 469 patients with advanced lung cancer. The study population includes both male and female participants. The age range is categorized by specific codes, indicating an adult population. Eligible individuals must have unresectable disease confirmed via histological or cytological examination. Included populations comprise those with non-small cell lung cancer (NSCLC) regardless of PD-L1 expression, as well as those with small cell lung cancer (SCLC). Key requirements for participation include measurable disease as defined by RECIST v1.1, an Eastern Cooperative Oncology Group performance status of 0 or 1, and a life expectancy of at least 12 weeks.
Plans and Procedures
This Phase Ib/II, multi-site, open-label, two-part trial is designed to evaluate the efficacy, safety, pharmacokinetics, and recommended combination dose of BNT324 and BNT327 in participants with advanced lung cancer. Part 1 involves a dose escalation phase to determine the recommended phase II dose by assessing safety and tolerability. Part 2 consists of dose optimization and signal seeking across multiple cohorts, including treatment-naive non-small cell lung cancer and relapsed or progressive small cell lung cancer. The study evaluates outcomes such as objective response rate, progression-free survival, and overall survival according to RECIST v1.1 criteria. Participants undergo a screening process to confirm histological or cytological evidence of unresectable disease and an Eastern Cooperative Oncology Group performance status of 0 or 1. The study includes assessments of treatment-emergent adverse events from the first dose until 90 days after the last dose or until the initiation of new anticancer therapy. Participation concludes upon the occurrence of specific clinical endpoints or the commencement of new therapeutic interventions.
Treatment
The investigational medicinal product BNT324 is supplied as a powder for concentrate for solution for injection/infusion. This orphan drug is administered via intravenous infusion.
The investigational medicinal product BNT327 is supplied as a powder for concentrate for solution for infusion. This orphan drug is administered via intravenous infusion.
The study evaluates the combination of BNT324 and BNT327 in participants with advanced lung cancer. The clinical trial is divided into two parts: a dose escalation phase to determine the recommended phase II dose and a dose optimization phase to assess the safety and efficacy of the combination therapy in cohorts with non-small cell lung cancer and small cell lung cancer.
Efficacy
Efficacy assessment in this study involves several parameters to evaluate the therapeutic effect of the combination of BNT324 and BNT327 in participants with advanced lung cancer. The primary efficacy endpoint for Part 2 cohorts 1 through 7 is the objective response rate, which is defined as the proportion of participants achieving a confirmed complete response or partial response as the best overall response. These responses are determined based on the investigator's assessment according to the response evaluation criteria in solid tumors (RECIST) version 1.1.
Secondary efficacy endpoints include the following:
- Disease control rate, representing the proportion of participants achieving a confirmed complete response, partial response, or stable disease.
- Progression-free survival, measured as the time from the first dose of the investigational medicinal product to the first occurrence of progressive disease or death from any cause.
- Duration of response, defined as the interval from the first objective response to the first occurrence of progressive disease or death.
- Overall survival, calculated as the time from the first dose to death from any cause.
- Time to response, which is the time from the first dose to the first objective response.
Inclusion and Exclusion Criteria
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 1.1.
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Recruiting | 15 Mar 2026 | 26 |
 Italy | Recruiting | 15 Mar 2026 | 30 |
 Poland | Recruiting | 15 Mar 2026 | 30 |
 Spain | Recruiting | 15 Mar 2026 | 26 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
BNT324 | Test | POWDER FOR CONCENTRATE FOR SOLUTION FOR INJECTION/INFUSION | INTRAVENOUS INFUSION | — | — | PRD11490025 |
BNT327 | Test | POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | — | — | PRD11607432 |