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Trial record 1 of 1 for:    NCT03696212
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Grapiprant (ARY-007) and Pembrolizumab in Patients With Advanced or Metastatic Post-PD-1/L1 NSCLC Adenocarcinoma

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ClinicalTrials.gov Identifier: NCT03696212
Recruitment Status : Recruiting
First Posted : October 4, 2018
Last Update Posted : April 5, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Arrys Therapeutics

Tracking Information
First Submitted Date  ICMJE October 3, 2018
First Posted Date  ICMJE October 4, 2018
Last Update Posted Date April 5, 2019
Actual Study Start Date  ICMJE January 8, 2019
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 3, 2018)
  • 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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 3, 2018)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
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 Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-small Cell Lung Cancer Adenocarcinoma
Intervention  ICMJE Drug: grapiprant and pembrolizumab
Participants will be administered 21-day cycles of oral grapiprant in combination with IV pembrolizumab
Other Names:
  • ARYS-007
  • MK-3475
  • KEYNOTE-888
Study Arms  ICMJE Experimental: grapiprant and pembrolizumab combination
Participants will be treated with grapiprant in combination with pembrolizumab.
Intervention: Drug: grapiprant and pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 3, 2018)
25
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE 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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Janine McDermott, MS 781-392-5556 janine.mcdermott@arrystherapeutics.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03696212
Other Study ID Numbers  ICMJE ARYS-002
Has Data Monitoring Committee No
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  ICMJE
Plan to Share IPD: Undecided
Responsible Party Arrys Therapeutics
Study Sponsor  ICMJE Arrys Therapeutics
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Study Director: Jeffrey Ecsedy Arrys Therapeutics
Study Director: Jason Sager, MD Arrys Therapeutics
PRS Account Arrys Therapeutics
Verification Date January 2019

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