NCT03522142终止1 期
A Phase 1a/1b Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 83
- 试验地点
- 18
- 主要终点
- Part 2 (2A & B): RDE in combination with INCMGA00012
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics, pharmacodynamics, and early clinical activity of single-agent INCB081776 (Part 1) and INCB081776 in combination with INCMGA00012 (Part 2).
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
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female participants at least 18 years of age with advanced malignancies who have received or been intolerant to standard therapy:
- •Parts 1A and 2A:
- •Histologically confirmed advanced or metastatic gastric or GEJ adenocarcinoma, HCC, melanoma, NSCLC, RCC, soft-tissue sarcoma, SCCHN (recurrent or metastatic), TNBC, or urothelial carcinoma. Additional tumor histologies, including MSI-H tumors, may be allowed with approval from the medical monitor.
- •Measurable disease per RECIST v1.
- •Parts 1B and 2B:
- •Histologic confirmation of the cohort-specific tumor types specified below: Cohort 1 - Advanced or metastatic melanoma Cohort 2 - Advanced or metastatic NSCLC Cohort 3 - Recurrent or metastatic SCCHN Cohort 4 - Advanced or metastatic soft-tissue sarcoma
- •Cohorts 1-3 must have received 1 prior PD-1/L1 treatment and have experienced PD during or after that treatment and have progressed on other SOC therapy(ies); Cohort 4 must be PD-1/L1 treatment naïve but have progressed on SOC therapy(ies).
- •Measurable disease per RECIST v1.
- •Must be willing to submit to a fresh baseline tumor biopsy and an on-treatment biopsy between Cycle 2 Day 1 and Cycle 3 Day
- •Care should be taken to biopsy the same lesion for the baseline and on-treatment samples. If a participant has a solitary target lesion, this should not be biopsied.
- •Participants with relapsed/refractory AML following standard therapy; acute promyelocytic leukemia (M3) and therapy-related AML are excluded.
- •FLT3-ITD and IDH1/2 wild-type or mutated are eligible; appropriate targeted therapy for participants with actionable mutations must have been received.
排除标准
- •Laboratory values not within the protocol-defined range.
- •History of retinal disease as defined in the protocol.
- •Clinically significant cardiac disease as per protocol-defined criteria.
- •History or presence of an ECG that, in the investigator's opinion, is clinically meaningful as per protocol-defined criteria.
- •Untreated brain or central nervous system (CNS) metastases or brain or CNS metastases that have progressed as per protocol-defined criteria.
- •Active or inactive autoimmune disease or syndrome that has required systemic treatment in the past 2 years or receiving systemic therapy for an autoimmune or inflammatory disease.
- •Prior Grade 3 or higher immune-related AEs or any ocular toxicity on prior immunotherapy as per protocol-defined criteria.
- •Receipt of any vitamin K antagonists, systemic corticosteroids, live vaccines, or treatment with any anticancer medications or investigational drugs within the protocol-defined intervals.
- •Has not recovered to ≤ Grade 1 or baseline from toxic effects of prior therapy and/or complications from prior surgical intervention before starting study treatment.
- •Active infection requiring systemic therapy.
- •Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.
- •Known history of HIV (HIV 1/2 antibodies).
研究组 & 干预措施
INCB081776
Experimental
Single-agent INCB081776.
干预措施: INCB081776 (Drug)
INCB081776 + INCMGA00012
Experimental
INCB081776 in combination with INCMGA00012.
干预措施: INCB081776 (Drug)
INCB081776 + INCMGA00012
Experimental
INCB081776 in combination with INCMGA00012.
干预措施: INCMGA00012 (Drug)
结局指标
主要结局
Part 2 (2A & B): RDE in combination with INCMGA00012
时间窗: Up to one year
Recommended dose as a combination as measured by safety, PK and data
Part 1 (1A and 1B): Recommended Dose for Expansion (RDE)
时间窗: Up to one year
Recommended dose as a monotherapy as measured by safety, PK and data
Part 2 (2A & 2B): Number of treatment-emergent adverse events
时间窗: Screening through 90 days after end of treatment, up to approximately 1 year
A TEAE is any adverse event (AE) either reported for the first time or worsening of a pre-existing event after first dose of study drug.
Part 1 (1A and 1B): Number of treatment-emergent adverse events (TEAEs)
时间窗: Screening through 90 days after end of treatment, up to approximately 1 year.
A TEAE is any adverse event (AE) either reported for the first time or worsening of a pre-existing event after first dose of study drug.
次要结局
- Part 1 and Part 2: Cmax of INCB081776(Up to approximately 3 weeks.)
- Part 1 and Part 2: Disease control rate(Up to approximately 1 year.)
- Part 1 and Part 2: Cmin of INCB081776(Up to approximately 3 weeks.)
- Part 1 and Part 2: Pharmacokinetic/ pharmacodynamic correlation(Up to approximately 3 weeks.)
- Part 1 and Part 2: Duration of response(Up to approximately 1 year.)
- Part 1 and Part 2 : λz of INCB081776(Up to approximately 3 weeks.)
- Part 1 and Part 2: Tmax of INCB081776(Up to approximately 3 weeks.)
- Part 1 and Part 2: AUC0-t of INCB081776(Up to approximately 3 weeks.)
- Part 1 and Part 2: t½ of INCB081776(Up to approximately 3 weeks.)
- Part 1 and Part 2: Overall response rate(Up to approximately 1 year.)
- Part 1 and Part 2: AUC0-∞ of INCB081776(Up to approximately 3 weeks.)
- Part 1 and Part 2 : CL/F of INCB081776(Up to approximately 3 weeks.)
- Part 1 and Part 2 : Vz/F of INCB081776(Up to approximately 3 weeks.)
研究者
研究点 (18)
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