A Phase Ib/II, multi-site, open-label, dose finding trial to evaluate the safety, efficacy, and pharmacokinetics of BNT326 in combination with BNT327 in participants with advanced non-small cell lung cancer (NSCLC)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- BioNTech SE
- 入组人数
- 24
- 试验地点
- 8
- 主要终点
- Part 1 - Occurrence of dose limiting toxicities (DLTs) within a participant during the DLT evaluation period
研究概览
简要总结
Part 1 – Dose Escalation: To determine the recommended phase 2 dose (RP2D) of BNT326 in combination with BNT327 by assessing the safety and tolerability in participants with advanced NSCLC. Part 2a – Dose Expansion: To assess the safety profile of BNT326 in combination with BNT327. To assess the efficacy of BNT326 in combination with BNT327. Part 2b – Dose Optimization: To assess the efficacy and determine the optimized dose of BNT326 in combination with BNT327.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Aged ≥18 years at the time of giving informed consent.
- •Have measurable disease defined by RECIST v1.
- •All participants have to provide a tumor tissue sample from archival tissue. Alternatively, a fresh biopsy should be collected, unless medically not justifiable to be conducted.
- •Have Eastern Cooperative Oncology Group performance status of 0 or
- •Have adequate organ and bone marrow function within 7 days before randomization/enrollment.
- •All parts: Have advanced non-squamous or squamous NSCLC.
排除标准
- •Had disease progression on or were intolerant to prior treatment with an agent targeting HER3 or with a topoisomerase I inhibitor payload. Note: For Part 2a Cohort A, prior exposure to agents targeting HER3 or topoisomerase I inhibitor payload may be allowed on a case-by-case basis after discussion with and approval by the sponsor.
- •Have urine protein ≥2+ and 24-hour urine protein excretion ≥1 g. If qualitative urine protein is ≤1+, a 24-hour urine protein quantitative test is not required.
- •Have a history of Grade ≥3 immune-related adverse events that led to treatment discontinuation of a prior checkpoint inhibitor.
- •Have clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
- •Participants with significant risks of hemorrhage or evidence of major coagulation disorders.
- •Have active or chronic corneal disorders or with any clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy.
- •Have an uncontrolled concomitant or intercurrent illness, that contraindicates study participation, limits compliance with study procedures or substantially increases the risk of incurring adverse events (AEs).
- •Have left ventricular ejection fraction < 50 % by either echocardiography or multi-gated acquisition within 28 days before randomization/enrollment.
- •Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization/enrollment.
- •Have a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- •Have had exposure to protocol-specific treatments with a washout period before randomization/enrollment.
- •Are participants of childbearing potential who are pregnant or breastfeeding or are planning pregnancy within the time specified in the protocol or are potentially fertile males, who are planning to father children during the study or within the time specified in the protocol.
- •Are subject to exclusion periods from another investigational study.
- •Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.
结局指标
主要结局
Part 1 - Occurrence of dose limiting toxicities (DLTs) within a participant during the DLT evaluation period
Part 1 - Occurrence of dose limiting toxicities (DLTs) within a participant during the DLT evaluation period
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)
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)
Part 1 and Part 2a - Occurrence of dose interruption, reduction, and discontinuation due to TEAEs
Part 1 and Part 2a - Occurrence of dose interruption, reduction, and discontinuation due to TEAEs
Part 2a and Part 2b - 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.
Part 2a and Part 2b - 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.
次要结局
- Part 1 – ORR: 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
- Part 2b - Occurrence of dose interruption, reduction, and discontinuation due to TEAEs
- Part 2a and Part 2b - Progression free survival based on the investigator's assessment: Defined as the time from first dose of IMP to the first objective tumor progression or death from any cause, whichever occurs first.
- Part 2a and Part 2b - Disease control rate: Defined as the proportion of participants with CR, PR, or stable disease as best overall response.
- Part 2a and Part 2b - Duration of response: 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 or death from any cause, whichever occurs first
- Part 2a and Part 2b - Time to response: Defined as the time from first dose of IMP to first confirmed objective response in participants with a confirmed objective response
- Part 2a and Part 2b - Overall survival: 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. 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. For applicable participants, if data permits.
- All cohorts - Anti-drug antibody (ADA) prevalence and ADA incidence. By cohort and combination treatment regimen for applicable participants.
研究者
Clinical Trial Information Desk
Scientific
BioNTech SE