NCT03696212终止1 期
Open Label, Single Arm, Phase 1b/2 Study to Evaluate the Safety and Efficacy of Grapiprant (ARY-007) in Combination With Pembrolizumab in Patients With Advanced or Metastatic Post-PD-1/L1 Non-Small Cell Lung Cancer (NSCLC) Adenocarcinoma
Arrys Therapeutics6 个研究点 分布在 1 个国家目标入组 18 人开始时间: 2019年1月8日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 18
- 试验地点
- 6
- 主要终点
- Safety and tolerability of grapiprant in combination with pembrolizumab
研究概览
简要总结
This study will be conducted in adult participants diagnosed with NSCLC who have been previously treated for a minimum of 12 weeks with any PD-1 or PD-L1 checkpoint inhibitor. This is a phase 1b/2, 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 disease response with grapiprant based on investigator assessments. Pharmacokinetics, pharmacodynamics and response biomarkers will also be assessed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 at least 18 years of age on day of signing informed consent
- •Histologically confirmed non-small cell lung cancer (NSCLC) adenocarcinoma
- •Advanced (stage IIIb) disease that is not amenable to curative intent treatment with concurrent chemoradiation and metastatic (stage IV) patients
- •Progressed clinically and/or radiographically per RECIST v1.1 after receiving a PD-1 or PD-L1 antagonist for a minimum of 12 weeks
- •Measurable disease per RECIST v1.1
- •Disease that can be safely accessed via bronchoscopic, thoracoscopic or percutaneous biopsy for multiple core biopsies and participant is willing to provide tissue from newly obtain biopsies on study in a subgroup of patients
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- •Adequate organ function
- •Highly effective birth control
- •Able to swallow and absorb oral tablets
排除标准
- •Current use of NSAIDs, COX-2 inhibitors
- •Known epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS gene alteration
- •No history of smoking (≤100 cigarettes lifetime)
- •History of severe hypersensitivity reactions to a PD-1/L1 antibody
- •Received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment or 5 half-lives, whichever is shorter
- •Received prior radiotherapy within 2 weeks of start of study treatment
- •Has received a live vaccine within 30 days prior to the first dose of study treatment
- •Taking strong CYP3A4 or P-glycoprotein inhibitors or inducers
- •Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment
- •Known additional malignancy that is progressing or has required active treatment within the past 3 years (with some permitted exceptions)
- •Known active CNS metastases and/or carcinomatous meningitis
- •Active autoimmune disease that has required systemic treatment in past 2 years
- •History of pneumonitis that required steroids or has current pneumonitis
- •Has an active infection requiring systemic therapy
- •Recent or current GI ulcer, colitis or non-immune colitis
- •Known history of human immunodeficiency virus (HIV) infection, or known active Hepatitis B, or Hepatitis C virus infection
- •Has had an allogeneic tissue/solid organ transplant
- •Clinically significant (i.e.active) cardiovascular disease
研究组 & 干预措施
grapiprant and pembrolizumab combination
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
Safety and tolerability of grapiprant in combination with pembrolizumab
时间窗: Up to 90 days after the end of treatment (average of 7 months)
Number of incidence, severity, relationship, concomitant medications administered, and duration of treatment emergent adverse events using CTCAE v5.0
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
Objective response rate (ORR)
时间窗: 7 months
Proportion of participants who achieved PR or better during the study per RECIST 1.1 and iRECIST
次要结局
- Progression-free survival (PFS)(Up to 12 months)
- Overall survival (OS)(Up to 2 years from start of study drug)
- Duration of treatment (DoT)(7 months)
- Disease control rate (DCR)(7 months)
- Duration of response (DoR)(Up to 12 months)
- PK of grapiprant: AUC(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: Cmax(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).)
- Plasma decay half-life (t1/2)(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).)
- Apparent oral clearance (CL/F)(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(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(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).)
- Pharmacodynamic immune effects in paired tumor biopsies(Predose through cycle 3 (each cycle is 21 days))
研究者
研究点 (6)
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