NCT03658772已完成1 期
An Open-label, Single-arm, Phase 1b Study to Evaluate the Safety and Efficacy of Grapiprant (ARY-007) in Combination With Pembolizumab in Patients With Advanced or Progressive Microsatellite Stable (MSS) Colorectal Cancer (CRC)
Arrys Therapeutics4 个研究点 分布在 1 个国家目标入组 54 人开始时间: 2018年9月20日最近更新:
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 54
- 试验地点
- 4
- 主要终点
- Define the recommended phase 2 dose (RP2D) of grapiprant combined with pembrolizumab
研究概览
简要总结
This study will be conducted in adult participants diagnosed with any form of an advanced or progressive MSS CRC for which 1st and 2nd line standard therapy (at least one of which contained fluorouracil) is no longer effective or is intolerable. This is a phase 1b, multi-center, open label study designed to assess safety and tolerability of grapiprant in combination with pembrolizumab, to determine the recommended phase 2 dose (RP2D) with pembrolizumab, and to evaluate and characterize the PK of grapiprant alone and in combination with pembrolizumab. Disease response, pharmacodynamics, and response biomarkers will also be assessed.
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
- •Male and female adult patients 18 years of age or older on day of signing informed consent.
- •Patients must have a histologically confirmed advanced, metastatic, or progressive Microsatellite Stable (MSS) Colorectal Cancer (CRC) per institutional standards.
- •Patient has received at least two prior lines of therapy for advanced or metastatic CRC, at least one of which included fluorouracil.
- •Highly effective birth control.
- •Measurable disease.
- •Accessible tumor that can be safely accessed for multiple core biopsies and patient is willing to provide tissue from newly obtain biopsies before and during treatment.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Adequate organ function.
- •Able to swallow and absorb oral tablets.
排除标准
- •Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
- •Current use of NSAIDs, COX-2 inhibitors and aspirin products within 3 days (preferably 7 days) before treatment initiation or at anytime during the study unless used for management of AE.
- •History of severe hypersensitivity reactions to chimeric or humanized antibodies
- •Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to treatment, or 5 half-lives, whichever is shorter.
- •Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
- •Known additional malignancy that is progressing or has required active treatment within the past 3 years.
- •Known active CNS metastases and/or carcinomatous meningitis.
- •Active autoimmune disease that has required systemic treatment in past 2 years.
- •History of non-infectious pneumonitis that required steroids or has current pneumonitis.
- •Active infection requiring systemic therapy.
- •Recent (within the last 12 months) or current GI ulcer, colitis or non-immune colitis.
- •Known history of human immunodeficiency virus (HIV) infection, Hepatitis B, or active Hepatitis C virus infection.
- •Clinically significant (i.e. active) cardiovascular disease
- •Allogeneic tissue/solid organ transplant
- •Medical conditions requiring concomitant administration of strong CYP3A4 or P glycoprotein inhibitors or inducers.
研究组 & 干预措施
Cohort 1
Experimental
Single Agent run-in with grapiprant and then combination treatment of grapiprant and pembrolizumab.
干预措施: grapiprant (Drug)
Cohort 1
Experimental
Single Agent run-in with grapiprant and then combination treatment of grapiprant and pembrolizumab.
干预措施: grapiprant and pembrolizumab (Drug)
Cohort 2
Experimental
Participants will be treated with grapiprant in combination with pembrolizumab.
干预措施: grapiprant and pembrolizumab (Drug)
结局指标
主要结局
Define the recommended phase 2 dose (RP2D) of grapiprant combined with pembrolizumab
时间窗: Through Cycle 1 (21 days)
Number, incidence and severity of treatment related adverse events as assessed by CTCAE 5.0
Safety and tolerability of grapiprant alone and in combination with pembrolizumab
时间窗: Up to 90 days after the end of treatment (average of 7 months)
Number of incidence, severity, and duration of treatment emergent adverse events using CTCAE v5.0
次要结局
- Plasma decay half-life (t1/2)(Safety Run-in (7 days); Days 1 and 2 of first 2 cycles (every 21 days), followed by Day 1 of every even cycle beginning with cycle 4 (every 42 days) through end of treatment (average of 4 months))
- PGEM as a pharmacodynamic and predictive biomarker(PreScreening through 7 months)
- Duration of Response (DOR)(7 months)
- Duration of treatment (DOT)(7 months)
- Overall Response Rate (ORR)(7 months)
- Progression -free survival (PFS)(Up to 12 months)
- Overall survival (OS)(Up to 2 years from start of study drug.)
- PK of grapiprant: AUC0 last(Safety Run-in (7 days); Days 1 and 2 of first 2 cycles (every 21 days), followed by Day 1 of every even cycle beginning with cycle 4 (every 42 days) through end of treatment (average of 4 months).)
- Peak to trough ratio(Safety Run-in (7 days); Days 1 and 2 of first 2 cycles (every 21 days), followed by Day 1 of every even cycle beginning with cycle 4 (every 42 days) through end of treatment (average of 4 months))
- PK of grapiprant: Tmax(Safety Run-in (7 days); Days 1 and 2 of first 2 cycles (every 21 days), followed by Day 1 of every even cycle beginning with cycle 4 (every 42 days) through end of treatment (average of 4 months))
- Disease control rate (DCR)(7 months)
- Serum tumor marker changes(7 months)
- Pharmacodynamic immune effects in paired tumor biopsies(predose through cycle 3 (each cycle is 21 days))
- Apparent oral clearance (CL/F)(Safety Run-in (7 days); Days 1 and 2 of first 2 cycles (every 21 days), followed by Day 1 of every even cycle beginning with cycle 4 (every 42 days) through end of treatment (average of 4 months))
- Observed accumulation ratio(Safety Run-in (7 days); Days 1 and 2 of first 2 cycles (every 21 days), followed by Day 1 of every even cycle beginning with cycle 4 (every 42 days) through end of treatment (average of 4 months))
研究者
研究点 (4)
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