Grapiprant (ARY-007) and Pembrolizumab in Patients With Advanced or Metastatic Post-PD-1/L1 NSCLC Adenocarcinoma

Sponsor:

Collaborators:

Information provided by (Responsible Party):

，

Tracking Information

First Submitted Date ^ICMJE

October 3, 2018

First Posted Date ^ICMJE

October 4, 2018

Last Update Posted Date

October 4, 2018

Actual Study Start Date ^ICMJE

October 31, 2018

Estimated Primary Completion Date

September 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Safety and tolerability of grapiprant in combination with pembrolizumab[ Time Frame: 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[ Time Frame: Through Cycle 1 (21 days) ]

Number, incidence and severity of treatment related adverse events as assessed by CTCAE 5.0

Objective response rate (ORR)[ Time Frame: 7 months ]

Proportion of participants who achieved PR or better during the study per RECIST 1.1 and iRECIST

Original Primary Outcome Measures ^ICMJE

Same as current

Current Secondary Outcome Measures ^ICMJE

Progression-free survival (PFS)[ Time Frame: Up to 12 months ]
Participants who discontinue treatment without disease progression
Overall survival (OS)[ Time Frame: Up to 2 years from start of study drug ]
Date of study drug to date of death due to any cause
Duration of treatment (DoT)[ Time Frame: 7 months ]
Disease response for time of duration on treatment
Disease control rate (DCR)[ Time Frame: 7 months ]
Percentage of patients who have achieved CR, PR and stable disease
Duration of response (DoR)[ Time Frame: Up to 12 months ]
Time from documentation of tumor response to disease progression per RECIST and iRECIST 1.1
PK of grapiprant: AUC[ Time Frame: 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). ]
Area under the plasma concentration-time curve
PK of grapiprant: Cmax[ Time Frame: 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 serum concentration of grapiprant
Plasma decay half-life (t1/2)[ Time Frame: 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). ]
Measurement of half-life of grapiprant after dosing
Apparent oral clearance (CL/F)[ Time Frame: 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). ]
Rate of elimination of the drug from plasma after oral administration
Peak to trough ratio[ Time Frame: 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). ]
Measure how drug effect is sustained over dose interval
Observed accumulation ratio[ Time Frame: 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). ]
Relationship between the dosing interval and the rate of elimination for the drug
Pharmacodynamic immune effects in paired tumor biopsies[ Time Frame: Predose through cycle 3 (each cycle is 21 days) ]
Asses changes in tumor infiltrating helper T cells, cytoxic T cells and regulatory monocyte/macrophages with study treatment

Descriptive Information

Brief Title ^ICMJE

Grapiprant (ARY-007) and Pembrolizumab in Patients With Advanced or Metastatic Post-PD-1/L1 NSCLC Adenocarcinoma

Official Title ^ICMJE

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

Brief Summary

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.

Detailed Description

Study Type ^ICMJE

Interventional

Study Phase

Phase 1/Phase 2

Study Design ^ICMJE

Allocation:
Intervention Model: Single Group Assignment
Intervention Model Description:
Masking: Interventional
Masking Description:
Primary Purpose: Treatment

Condition ^ICMJE

Intervention ^ICMJE

Drug: grapiprant and pembrolizumab
Participants will be administered 21-day cycles of oral grapiprant in combination with IV pembrolizumab

Study Arms

Experimental: grapiprant and pembrolizumab combination
Participants will be treated with grapiprant in combination with pembrolizumab.

Recruitment Information

Recruitment Status ^ICMJE

Not yet recruiting

Estimated Enrollment ^ICMJE

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date

September 2020

Estimated Primary Completion Date

September 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Key Inclusion Criteria: - 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 Key Exclusion Criteria: - Current use of NSAIDs, COX-2 inhibitors - Known epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS gene alteration, BRAF gene mutation - 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 - 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, Hepatitis B, or active Hepatitis C virus infection - Clinically significant (i.e.active) cardiovascular disease

Sex/Gender

Sexes Eligible for Study:

All

Ages

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Listed Location Countries ^ICMJE

United States

Removed Location Countries

Administrative Information

Has Data Monitoring Committee

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

Plan to Share IPD:

Undecided

Responsible Party

，

Study Sponsor ^ICMJE

Arrys Therapeutics

Collaborators ^ICMJE

Investigators ^ICMJE

Study Director: Jeffrey Ecsedy Arrys Therapeutics
Study Director: Jason Sager, MD Arrys Therapeutics

PRS Account

Verification Date

October 2018

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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