A Phase 1, Open-Label, Multicenter Study of INCB161734 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 710
- 试验地点
- 49
- 主要终点
- Number of participants with Dose Limiting Toxicities (DLTs)
研究概览
简要总结
This study is conducted to determine the safety and tolerability of INCB161734 as a single agent or in combination with other anticancer therapies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •≥18 years old.
- •Locally advanced or metastatic solid tumor with KRAS G12D mutation.
- •For Part 1a and Part 2 Combination Groups 1, 2, and 7: Disease progression on prior standard treatment, intolerance to or ineligibility for standard treatment, declined available therapies that are known to confer clinical benefit, or no standard available treatment to improve the disease outcome.
- •Cohort specific requirements aas defined in the protocol.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
排除标准
- •Prior treatment with any KRAS G12D inhibitor
- •Known additional invasive malignancy within 1 year of the first dose of study drug
- •History of organ transplant, including allogeneic stem cell transplantation
- •Significant, uncontrolled medical condition
- •History or presence of an ECG abnormality
- •Inadequate organ function
- •Other protocol-defined Inclusion/Exclusion Criteria may apply
研究组 & 干预措施
Part 1a: Dose Escalation monotherapy
INCB161734 at the protocol-defined dose strength based on cohort assignment.
干预措施: INCB161734 (Drug)
Part 2b: Dose Expansion combination
INCB161734 in combination at the protocol-defined dose strength based on cohort assignment.
干预措施: Retifanlimab (Drug)
Part 2a: Dose Escalation combination
INCB161734 in combination at the protocol-defined dose strength based on cohort assignment.
干预措施: GEMNabP (Drug)
Part 2a: Dose Escalation combination
INCB161734 in combination at the protocol-defined dose strength based on cohort assignment.
干预措施: mFOLFIRINOX (Drug)
Part 2a: Dose Escalation combination
INCB161734 in combination at the protocol-defined dose strength based on cohort assignment.
干预措施: FOLFOX (Drug)
Part 2a: Dose Escalation combination
INCB161734 in combination at the protocol-defined dose strength based on cohort assignment.
干预措施: INCB161734 (Drug)
Part 2a: Dose Escalation combination
INCB161734 in combination at the protocol-defined dose strength based on cohort assignment.
干预措施: Cetuximab (Drug)
Part 2a: Dose Escalation combination
INCB161734 in combination at the protocol-defined dose strength based on cohort assignment.
干预措施: FOLFIRI (Drug)
Part 2a: Dose Escalation combination
INCB161734 in combination at the protocol-defined dose strength based on cohort assignment.
干预措施: Retifanlimab (Drug)
Part 1b: Dose Expansion monotherapy
INCB161734 at the protocol-defined dose strength based on cohort assignment.
干预措施: INCB161734 (Drug)
Part 1c: Pharmacodynamic cohort
INCB161734 at the protocol-defined dose strength based on cohort assignment.
干预措施: INCB161734 (Drug)
Part 2b: Dose Expansion combination
INCB161734 in combination at the protocol-defined dose strength based on cohort assignment.
干预措施: GEMNabP (Drug)
Part 2b: Dose Expansion combination
INCB161734 in combination at the protocol-defined dose strength based on cohort assignment.
干预措施: mFOLFIRINOX (Drug)
Part 2b: Dose Expansion combination
INCB161734 in combination at the protocol-defined dose strength based on cohort assignment.
干预措施: FOLFOX (Drug)
Part 2b: Dose Expansion combination
INCB161734 in combination at the protocol-defined dose strength based on cohort assignment.
干预措施: Cetuximab (Drug)
Part 2b: Dose Expansion combination
INCB161734 in combination at the protocol-defined dose strength based on cohort assignment.
干预措施: FOLFIRI (Drug)
Part 1d: Food-Effect
Evaluate food effect on drug exposure as defined in the protocol.
干预措施: INCB161734 (Drug)
Part 2b: Dose Expansion combination
INCB161734 in combination at the protocol-defined dose strength based on cohort assignment.
干预措施: INCA33890 (Drug)
Part 2a: Dose Escalation combination
INCB161734 in combination at the protocol-defined dose strength based on cohort assignment.
干预措施: INCA33890 (Drug)
Part 2b: Dose Expansion combination
INCB161734 in combination at the protocol-defined dose strength based on cohort assignment.
干预措施: INCB161734 (Drug)
结局指标
主要结局
Number of participants with Dose Limiting Toxicities (DLTs)
时间窗: Up to 28 days
Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.
Number of participants with TEAEs leading to dose modification or discontinuation
时间窗: Up to 2 years and 90 days
Number of participants with TEAEs leading to dose modification or discontinuation.
Number of participants with Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to 2 years and 90 days
Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug monotherapy and in combination with cetuximab and retifanlimab.
次要结局
- INCB161734 pharmacokinetic (PK) in Plasma(Up to approximately 90 days)
- Duration of Response (DOR)(Up to 2 years)
- Objective Response Rate (ORR)(Up to 2 years)
- Disease Control Response (DCR)(Up to 2 years)