A Phase 1/2 Study of INCB099280 in Combination With Axitinib in Adults With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 12
- 主要终点
- Part 1: Number of participants with Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
This study is being conducted to evaluate the safety and tolerability of INCB099280 in combination with axitinib and to assess the antitumor activity of INCB099280 in combination with axitinib. This study will only be open in the UK and EU.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed advanced solid tumors (protocol-defined select solid tumors) with measurable lesions per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) that are considered non-amenable to surgery or other curative treatments or procedures.
- •Must have disease progression on or after treatment with at least one prior systemic chemotherapy.
- •Eastern Cooperative Oncology Group performance status score of 0 or
- •Life expectancy > 12 weeks.
- •Willingness to avoid pregnancy.
排除标准
- •Known additional malignancy that is progressing or requires active treatment.
- •Central nervous system (CNS) metastases requiring treatment and/or leptomeningeal disease.
- •Toxicity from prior therapy that has not recovered to protocol-defined limits.
- •Prior receipt of an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent; treatment with an immune modulator (eg, CTLA-4, GITR, LAG3, TIM3, OX40, ICOS, IL-2, 4-1BB, CAR-T cell).
- •Prior therapy with antiangiogenic small-molecule TKIs targeting the VEGF pathway
- •Participation in another interventional clinical study while receiving INCB
- •Impaired cardiac function or clinically significant cardiac disease.
- •History or evidence of interstitial lung disease including noninfectious pneumonitis.
- •Presence of gastrointestinal conditions that may affect drug absorption.
- •Any autoimmune disease requiring systemic treatment in the past 5 years.
- •Diagnosis of primary immunodeficiency or receiving chronic systemic steroid therapy at a daily dose exceeding 10 mg of prednisone or equivalent.
- •Active infection requiring systemic therapy.
- •History of organ transplantation, including stem cell transplantation.
- •Receipt of systemic antibiotics within 28 days of first dose of study treatment.
- •Probiotic usage is prohibited during screening and throughout the study treatment period.
- •Received a live vaccine within 28 days of the planned start of study drug.
- •Laboratory values outside the Protocol-defined ranges.
- •Inadequate organ function.
- •Other protocol-defined Inclusion/Exclusion Criteria may apply.
研究组 & 干预措施
Part 1: Dose Escalation
Up to 6 doses of INCB099280 administered twice daily (BID) in combination with axitinib BID will be evaluated to identify dose(s) for further evaluation in the dose expansion phase of the study.
干预措施: INCB099280 (Drug)
Part 2: Dose Expansion
On completion of Part 1, participants will be enrolled in 1 of 2 disease-specific cohorts: Cohort 1: Adults with clear-cell gynecological cancers with at least 50% clear-cell histology whose disease progressed on or following at least 1 prior line of systemic chemotherapy and are not candidates for curative surgery or (chemo)radiation. Cohort 2: Adults with rare histological subtype epithelial cancers of the gynecological tract whose disease progressed on or following at least 1 prior line of systemic chemotherapy and are not candidates for curative surgery or (chemo)radiation. One or two doses may be selected from Part 1 for each cohort in the Part 2 Expansion.
干预措施: INCB099280 (Drug)
Part 1: Dose Escalation
Up to 6 doses of INCB099280 administered twice daily (BID) in combination with axitinib BID will be evaluated to identify dose(s) for further evaluation in the dose expansion phase of the study.
干预措施: axitinib (Drug)
Part 2: Dose Expansion
On completion of Part 1, participants will be enrolled in 1 of 2 disease-specific cohorts: Cohort 1: Adults with clear-cell gynecological cancers with at least 50% clear-cell histology whose disease progressed on or following at least 1 prior line of systemic chemotherapy and are not candidates for curative surgery or (chemo)radiation. Cohort 2: Adults with rare histological subtype epithelial cancers of the gynecological tract whose disease progressed on or following at least 1 prior line of systemic chemotherapy and are not candidates for curative surgery or (chemo)radiation. One or two doses may be selected from Part 1 for each cohort in the Part 2 Expansion.
干预措施: axitinib (Drug)
结局指标
主要结局
Part 1: 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.
Part 1: Number of participants with Dose Limiting Toxicities (DLTs)
时间窗: Up to 21 days
Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.
Part 1: Number of participants with TEAEs leading to dose modification
时间窗: Up to 2 years
Number of participants with TEAEs leading to a dose modification (treatment interruption, dose reduction, and permanent discontinuation of either study drug).
Part 2: Objective response rate (ORR)
时间窗: Up to 2 years
Defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR), as determined by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
次要结局
- Part 2: Number of participants with Treatment-emergent Adverse Events (TEAEs)(Up to 2 years and 90 days)
- INCB099280 and axitinib plasma concentrations.(Up to 2 years)
- Disease Control Rate (DCR)(Up to 2 years)
- Part 1: Objective response rate (ORR)(Up to 2 years)
- Duration of Response (DOR)(Up to 2 years)
- Part 2: Number of participants with TEAEs leading to dose modification(Up to 2 years)