A Phase 1/1b Study of IAM1363 in Participants With Advanced Cancers Harboring HER2 Alterations
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 383
- 试验地点
- 80
- 主要终点
- Pharmacokinetic (PK) parameters (Parts 1 and 2 only)
研究概览
简要总结
This is a Phase 1/1b open-label, multi-center dose escalation and dose optimization study designed to evaluate the safety and preliminary efficacy of IAM1363 in participants with advanced cancers that harbor HER2 alterations.
详细描述
This is a Phase 1/1b open-label, multi-center study, designed to evaluate IAM1363 in participants with advanced cancers that harbor HER2 alterations.
This study consists of the following 4 parts:
- Part 1 (Monotherapy Dose Escalation)
- Part 2 (Dose Optimization)
- Part 3 (Dose Expansion)
- Part 4 (Combination Cohorts)
Part 1 will enroll participants with a confirmed, relapsed/refractory malignancy with documented diagnosis of HER2 alterations including participants with brain metastases. Once a provisional maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) has been determined, Part 2 will enroll additional cohorts to optimize dose selection and to further evaluate the safety and preliminary efficacy of IAM1363. Following completion of Dose Optimization, Part 3 will be opened to enroll tumor-specific cohorts utilizing a Simon 2-Stage Minimax Design to evaluate IAM1363 at the selected dose(s).
Part 4 will enroll 4 cohorts of participants who will receive IAM1363 in combination with other anti-cancer agents.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Have relapsed/refractory HER2-altered malignancy; for selected cohorts, prospective confirmation of HER2 alteration by central testing is required
- •Have progression of disease after the last systemic therapy, or be intolerant of last systemic therapy
- •Have radiographically measurable disease by RECIST v1.1 and/or RANO-BM
- •Eastern Cooperative Oncology Group (ECOG) performance score 0-1
- •Have adequate baseline hematologic, liver and renal function
- •Have left ventricular ejection fraction (LVEF) ≥ 50%
- •Able to swallow oral medication
排除标准
- •Clinically significant cardiac disease
- •Infection with human immunodeficiency virus (HIV)-1 or HIV-
- •Exception: Participants with well-controlled HIV (e.g., CD4 >350/mm3 and undetectable viral load) are eligible
- •Current active liver disease including hepatitis A, hepatitis B , or hepatitis C
- •Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant small bowel resection that would preclude adequate absorption
- •Uncontrolled diabetes
- •History of solid organ transplantation
- •History of Grade ≥2 CNS hemorrhage, or any CNS hemorrhage within 28 days before C1D1
- •Prior history of non-infectious interstitial lung disease (ILD). (Exceptions: participants with prior grade 1 ILD that has completely resolved are eligible)
- •Participants requiring immediate local therapy for brain metastases
研究组 & 干预措施
IAM1363 Monotherapy or Combination Therapy
Treatment with IAM1363 capsules, dosed orally alone or in combination with other anti-cancer agents, in 14- or 21-day cycles.
干预措施: IAM1363 (Drug)
结局指标
主要结局
Pharmacokinetic (PK) parameters (Parts 1 and 2 only)
时间窗: Up to 42 days
PK parameters in participants in Parts 1 and 2. Includes but is not limited to assessment of maximum concentration (Cmax).
Incidence and severity of dose limiting toxicities (DLTs) (Part 1 only)
时间窗: 21 days
Incidence and severity of DLTs during the first cycle of treatment in participants in Part 1
Incidence and severity of adverse events (AEs) (Parts 1 and 2 only)
时间窗: Through 30 days after the last dose of study drug
Incidence of treatment emergent AEs (TEAEs) and serious adverse events (SAEs) in participants in Parts 1 and 2
Confirmed objective response rate (cORR) (Part 3 only)
时间窗: Through study completion, estimated as 46 months
Percentage of participants in Part 3 who achieve a confirmed objective response (complete response \[CR\] + partial response \[PR\]) per the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
Confirmed central nervous system ORR (CNS-cORR) (Part 3 Only)
时间窗: Through study completion, estimated as 46 months
Percentage of participants in Part 3 who achieve a confirmed CNS-cORR (CNS-CR + CNS-PR) per the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) Criteria
Incidence and severity of adverse events (AEs)
时间窗: Through 30 days after the last dose of study drug
Incidence of treatment emergent AEs (TEAEs) and serious adverse events (SAEs)
Pharmacokinetic (PK) parameters
时间窗: Up to 42 days
PK parameters. Includes but is not limited to assessment of maximum concentration (Cmax).
Confirmed objective response rate (cORR)
时间窗: Through study completion, estimated as 46 months
Percentage of participants who achieve a confirmed objective response (complete response \[CR\] + partial response \[PR\]) per the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
Confirmed central nervous system ORR (CNS-cORR)
时间窗: Through study completion, estimated as 46 months
Percentage of participants who achieve a confirmed CNS-cORR (CNS-CR + CNS-PR) per the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) Criteria
Frequency of IAM1363 dose modifications, including treatment discontinuations
时间窗: Through 30 days after the last dose of study drug
Incidence and severity of clinical laboratory abnormalities
时间窗: Through 30 days post last dose of study drug
Incidence of ECG abnormalities
时间窗: Through 30 days after the last dose of study drug
As measured using standard ECG parameters, including pulse rate, QT intervals, and QRS duration.
次要结局
- PK parameters (Part 3 only)(Up to 42 days)
- Incidence and severity of clinical laboratory abnormalities(Through 30 days after the last dose of study drug)
- Incidence of electrocardiogram (ECG) abnormalities(Through 30 days after the last dose of study drug)
- cORR (Parts 1 and 2 only)(Through study completion, estimated as 46 months)
- Overall survival (OS)(Through study completion, estimated as 46 months)
- Incidence and severity of AEs (Part 3 Only)(Through 30 days after the last dose of study drug)
- Anti-tumor activity against CNS/brain metastases(Through study completion, estimated as 46 months)
- Clinical benefit rate (CBR)(Through study completion, estimated as 46 months)
- Best overall response (BoR) rate(Through study completion, estimated as 46 months)
- Duration of response (DoR)(Through study completion, estimated as 46 months)
- Disease control rate (DCR)(Through study completion, estimated as 46 months)
- Progression-free survival (PFS)(Through study completion, estimated as 46 months)