A Phase 1, Open-Label, Multicenter Study of INCB186748 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 30
- 试验地点
- 9
- 主要终点
- Number of participants with Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The purpose of this study is to evaluate INCB186748 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation.
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 1 and Part 2 Combination Group 1: Disease progression on or after prior standard treatment, or intolerance to or ineligibility for standard treatment, or no standard available treatment to improve the disease outcome.
- •For Part 2 Combination Groups 2 and 3: No more than 1 prior standard treatment.
- •Cohort-specific requirements as follows:
- •Parts 1a and 1d: histologically or cytologically confirmed malignant solid tumor of any tissue origin.
- •Disease Group 1: diagnosis of PDAC and at least 1 but no more than 2 prior standard systemic regimens for pancreatic cancer.
- •Disease Group 2: diagnosis of CRC.
- •Part 1c: Confirmed diagnosis of PDAC or CRC.
- •Parts 2a and 2b
- •Combination Group 1 (INCB186748 in combination with cetuximab):
- •Diagnosis of PDAC or
- •Diagnosis of CRC and ∘ Prior treatment in the advanced setting with a fluoropyrimidine-based chemotherapy regimen containing either oxaliplatin or irinotecan and
- •In Part 2a: ≤ 3 prior standard regimens.
- •In Part 2b: ≤ 2 prior standard regimens.
- •Combination Group 2 (INCB186748 in combination with GEMNabP) and
- •Combination Group 3 (INCB186748 in combination with mFOLFIRINOX):
- •Diagnosis of PDAC.
- •≤ 1 prior standard systemic regimen for pancreatic cancer.
- •Measurable disease according to RECIST v1.
- •ECOG performance status score of 0 or 1.
排除标准
- •Prior treatment with any KRAS 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
INCB186748 at the protocol-defined dose strength based on cohort assignment.
干预措施: INCB186748 (Drug)
Part 1b: Dose Expansion monotherapy
INCB186748 at the protocol-defined dose strength based on cohort assignment.
干预措施: INCB186748 (Drug)
Part 1c: Pharmacodynamic cohort
INCB186748 at the protocol-defined dose strength based on cohort assignment.
干预措施: INCB186748 (Drug)
Part 1d: Food-Effect
Evaluate food effect on drug exposure as defined in the protocol.
干预措施: INCB186748 (Drug)
Part 2a: Dose Escalation combination
INCB186748 in combination at the protocol-defined dose strength based on cohort assignment.
干预措施: INCB186748 (Drug)
Part 2a: Dose Escalation combination
INCB186748 in combination at the protocol-defined dose strength based on cohort assignment.
干预措施: Cetuximab (Drug)
Part 2a: Dose Escalation combination
INCB186748 in combination at the protocol-defined dose strength based on cohort assignment.
干预措施: GEMNabP (Drug)
Part 2a: Dose Escalation combination
INCB186748 in combination at the protocol-defined dose strength based on cohort assignment.
干预措施: mFOLFIRINOX (Drug)
Part 2b: Dose Expansion combination
INCB186748 in combination at the protocol-defined dose strength based on cohort assignment.
干预措施: INCB186748 (Drug)
Part 2b: Dose Expansion combination
INCB186748 in combination at the protocol-defined dose strength based on cohort assignment.
干预措施: Cetuximab (Drug)
Part 2b: Dose Expansion combination
INCB186748 in combination at the protocol-defined dose strength based on cohort assignment.
干预措施: GEMNabP (Drug)
Part 2b: Dose Expansion combination
INCB186748 in combination at the protocol-defined dose strength based on cohort assignment.
干预措施: mFOLFIRINOX (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 Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to approximately 12 months and 60 days
Defined as adverse events reported for the first time or worsening of a pre-existing event occurring after the first dose of study drug up to 30 days (for INCB186748 as monotherapy and in combination with GEMNabP or mFOLFIRINOX) and 60 days (for INCB186748 in combination with cetuximab) after the last dose of INCB186748.
Number of participants with TEAEs leading to dose modification or discontinuation
时间窗: Up to approximately 12 months and 60 days
Number of participants with TEAEs leading to dose modification or discontinuation.
次要结局
- INCB186748 pharmacokinetic (PK) in Plasma(Up to approximately 12 months)
- Objective Response Rate (ORR)(Up to approximately 12 months)
- Disease Control Response (DCR)(Up to approximately 12 months)
- Duration of Response (DOR)(Up to approximately 12 months)