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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

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.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Adenocarcinoma Drug: grapiprant and pembrolizumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : January 8, 2019
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: grapiprant and pembrolizumab combination
Participants will be treated with grapiprant in combination with pembrolizumab.
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




Primary Outcome Measures :
  1. 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

  2. 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

  3. 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


Secondary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: Up to 12 months ]
    Participants who discontinue treatment without disease progression

  2. 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

  3. Duration of treatment (DoT) [ Time Frame: 7 months ]
    Disease response for time of duration on treatment

  4. Disease control rate (DCR) [ Time Frame: 7 months ]
    Percentage of patients who have achieved CR, PR and stable disease

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03696212


Contacts
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Contact: Janine McDermott, MS 781-392-5556 janine.mcdermott@arrystherapeutics.com

Locations
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United States, California
Stanford University Medical Center Recruiting
Stanford, California, United States, 94305
Contact: Melanie San Pedro    650-724-1388    msanpedro@stanford.edu   
United States, Michigan
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Amanda Newman    313-576-8411    newmana@karmanos.org   
United States, Pennsylvania
University of Pennsylvania Abramson Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Melissa Volpe    215-220-9703    Melisssa.volpe@uphs.upenn.edu   
Contact: Alison Berry, MBA    215-662-2847    Alison.Berry@uphs.upenn.edu   
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Irini Jorgi    215-728-5623    Irini.jorgi@fccc.edu   
Contact: Halyna Matviyishyn, RN, BSN    215-214-1727    Halyna.Matviyishyn@fccc.edu   
United States, Virginia
Virginia Cancer Specialists Recruiting
Fairfax, Virginia, United States, 22031
Contact: Claudia Phillips, RN, BSN, OCN, CCRP    703-208-9268    claudia.phillops@usoncology.com   
Sponsors and Collaborators
Arrys Therapeutics
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Jeffrey Ecsedy Arrys Therapeutics
Study Director: Jason Sager, MD Arrys Therapeutics

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Responsible Party: Arrys Therapeutics
ClinicalTrials.gov Identifier: NCT03696212     History of Changes
Other Study ID Numbers: ARYS-002
First Posted: October 4, 2018    Key Record Dates
Last Update Posted: April 5, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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

Additional relevant MeSH terms:
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Pembrolizumab
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Adenocarcinoma
Adenocarcinoma of Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antineoplastic Agents, Immunological
Antineoplastic Agents