A Phase I/II, multi-site, open-label, two-part trial to evaluate the efficacy, safety, and pharmacokinetics of BNT323 in combination with BNT327 in participants with advanced breast cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- BioNTech SE
- 入组人数
- 95
- 试验地点
- 18
- 主要终点
- Part 1 - Occurrence of dose limiting toxicities (DLTs) during the DLT evaluation period (Cycle 1), by dose level.
研究概览
简要总结
Dose escalation (Part I): To determine the recommended Phase 2 dose (RP2D) of BNT323 in combination with BNT327 by assessing safety. Dose optimization (Part II): To assess the efficacy and safety of BNT323 monotherapy, BNT327 monotherapy, and BNT323 in combination with BNT327 in terms of objective response rate (ORR).
研究设计
- 分配方式
- Randomized
- 主要目的
- Part 2 - Dose Optimization
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Have pathologically documented breast cancer (BC) that: is locally advanced, unresectable or metastatic; has a confirmed human epidermal growth factor receptor 2 (HER2) status as determined by the local laboratory (Part I, Part 2 Cohorts 2 and 4) or the central laboratory (Part II Cohorts 1 and 3) from the most recently collected pre-randomization tumor sample; has a documented history of HER2 expression consistent with the subgroup definitions
- •Have measurable disease defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
- •Has left ventricular ejection fraction (LVEF) greater than or equal to 55% by either echocardiography (ECHO) or multi-gated acquisition (MUGA) within 28 days before randomization/enrollment
排除标准
- •Have history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP
- •Have an uncontrolled intercurrent illness that would limit compliance with trial requirement or substantially increase risk of incurring adverse events (AEs)
- •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 steroid, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
- •Had prior treatment with topoisomerase I inhibitors, including antibody-drug conjugate (ADCs) with topoisomerase I inhibitor payloads such as trastuzumab deruxtecan (T-DXd)
- •Participants who have previously been randomized to or received treatment in a previous trial with BNT323, regardless of treatment assignment
- •Participants who received prior treatment with a programmed death 1/ vascular endothelial growth factor (PD-L1/VEGF) bispecific antibody
- •Participants who have received other systemic immunostimulatory agents or immunosuppressive therapies within 4 weeks prior to the initiation of trial treatment or are within five half-lives of the treatment drug (whichever is longer)
- •Participants who have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 3 weeks prior to the initiation of trial treatment
结局指标
主要结局
Part 1 - Occurrence of dose limiting toxicities (DLTs) during the DLT evaluation period (Cycle 1), by dose level.
Part 1 - Occurrence of dose limiting toxicities (DLTs) during the DLT evaluation period (Cycle 1), by dose level.
Occurrence of Treatment-emergent adverse events (TEAEs), Grade greater than or equal to 3 TEAEs, serious adverse events (SAEs), treatment-related TEAEs, treatment-related Grade greater than or equal to 3 TEAEs, and treatment-related SAEs. In Part 1 by dose level. In Part 2 by cohort and arm.
Occurrence of Treatment-emergent adverse events (TEAEs), Grade greater than or equal to 3 TEAEs, serious adverse events (SAEs), treatment-related TEAEs, treatment-related Grade greater than or equal to 3 TEAEs, and treatment-related SAEs. In Part 1 by dose level. In Part 2 by cohort and arm.
Occurrence of dose interruption, reduction, and discontinuation due to TEAEs In Part 1 by dose level. In Part 2 by cohort and arm.
Occurrence of dose interruption, reduction, and discontinuation due to TEAEs In Part 1 by dose level. In Part 2 by cohort and arm.
Part 2 - 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, by cohort and arm.
Part 2 - 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, by cohort and arm.
次要结局
- Part 1 - ORR defined as the proportion of participants in whom a confirmed CR or PR is observed as best overall response, by dose level.
- Part 2 - Duration of response (DoR) defined as the time from first objective response to first occurrence of objective tumor progression or death from any cause, whichever occurs first, by cohort and arm.
- Part 2 - Disease control rate (DCR) defined as the proportion of participants with confirmed CR, PR, or stable disease as best overall response, by cohort and arm.
- Part 2 - Time to response (TTR) defined as the time from first dose of IMP to first objective response, by cohort and arm.
- Part 2 Cohort 1 only - Progression free survival (PFS) 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, by arm.
研究者
Clinical Trial Information Desk
Scientific
BioNTech SE