A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Efficacy of INCB001158 in Combination With Chemotherapy, in Subjects With Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 149
- 试验地点
- 10
- 主要终点
- Phases 1 and 2: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
研究概览
简要总结
The purpose of this open-label nonrandomized Phase 1/2 study is to evaluate INCB001158 in combination with chemotherapy in participants with advanced/metastatic solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Histologically or cytologically confirmed diagnosis of selected advanced or metastatic solid tumors.
- •Presence of measurable disease per RECIST v1.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Baseline archival tumor specimen available or willingness to undergo a pretreatment tumor biopsy to obtain the specimen.
- •Resolution of treatment-related toxicities.
- •Adequate hepatic, renal, cardiac, and hematologic function.
- •Additional cohort-specific criteria may apply.
排除标准
- •Subjects who participated in any other study in which receipt of an investigational study drug or device occurred within 28 days or 5 half-lives (whichever is longer) prior to first dose.
- •Has received a prior monoclonal antibody within 4 weeks or 5 half-lives (whichever is shorter) before administration of study drug.
- •Has had prior chemotherapy or targeted small molecule therapy within 2 weeks before administration of study treatment.
- •Has received prior approved radiotherapy within 14 days of study therapy.
- •Has had known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry.
- •Has an active autoimmune disease that has required systemic treatment in past 2 years.
- •Has an active infection requiring systemic therapy.
- •Has known active CNS metastases and/or carcinomatous meningitis.
- •Women who are pregnant or breastfeeding.
研究组 & 干预措施
Treatment Group B
INCB001158 + gemcitabine/cisplatin
干预措施: Gemcitabine (Drug)
Treatment Group B
INCB001158 + gemcitabine/cisplatin
干预措施: Cisplatin (Drug)
Treatment Group A
INCB001158 + FOLFOX
干预措施: INCB001158 (Drug)
Treatment Group A
INCB001158 + FOLFOX
干预措施: Oxaliplatin (Drug)
Treatment Group A
INCB001158 + FOLFOX
干预措施: Leucovorin (Drug)
Treatment Group A
INCB001158 + FOLFOX
干预措施: 5-Fluorouracil (Drug)
Treatment Group B
INCB001158 + gemcitabine/cisplatin
干预措施: INCB001158 (Drug)
Treatment Group C
INCB001158 + paclitaxel
干预措施: INCB001158 (Drug)
Treatment Group C
INCB001158 + paclitaxel
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Phases 1 and 2: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
时间窗: up to 1385 days
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.
Phase 1: Number of Participants With Any Dose-limiting Toxicity (DLT)
时间窗: up to Day 28
A DLT was defined as the occurrence of any protocol-defined toxicity occurring up to and including Day 28, except those with a clear alternative explanation (e.g., disease progression) or transient (≤72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination. All DLTs were assessed by the investigator using Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria.
Recommended Phase 2 Dose (RP2D) of INCB001158 When Given in Combination With Each Chemotherapy Regimen
时间窗: up to Day 580
The RP2D of the combination of INCB001158 and chemotherapy in 21-day (for gemcitabine/cisplatin) or 28-day (for mFOLFOX6 or paclitaxel) treatment cycles in participants with advanced or metastatic solid tumors was determined. After the dose escalation was completed, the INCB001158 dose level that was pharmacologically active and tolerable in combination with each chemotherapy regimen (i.e., maximum tolerated dose or lower) was determined to be the RP2D. The RP2D was then further assessed in tumor expansion cohorts in Phase 2.
Phase 2: Objective Response Rate (ORR)
时间窗: up to 1385 days
ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR), as determined by investigator assessment of radiographic disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Analysis was conducted by cohort (tumor type) in Phase 2 because different tumor types could have different response criteria or different background response rates.
次要结局
- Phase 1: ORR(up to 580 days)
- Phases 1 and 2: Duration of Response(up to 368 days)
- Phases 1 and 2: Disease Control Rate(up to 1385 days)
- Phases 1 and 2: Progression-free Survival(up to 1385 days)
- Cmin of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy on Cycle 2 Day 1 Following Repeated Dose Administration(Day 1 of Cycle 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycle 2: predose; 1 and 4 hours post-dose for sparse sample collection)
- Cmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration(Day 1 of Cycles 1 and 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycles 1 and 2: predose; 1 and 4 hours post-dose for sparse sample collection)
- Tmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration(Day 1 of Cycles 1 and 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycles 1 and 2: predose; 1 and 4 hours post-dose for sparse sample collection)
- AUC0-t of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration(Day 1 of Cycles 1 and 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycles 1 and 2: predose; 1 and 4 hours post-dose for sparse sample collection)
- Tlast of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration(Day 1 of Cycles 1 and 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycles 1 and 2: predose; 1 and 4 hours post-dose for sparse sample collection)