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History of Changes for Study: NCT03658772
Grapiprant and Pembrolizumab in Patients With Advanced or Progressive MSS Colorectal Cancer
Latest version (submitted April 21, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 September 3, 2018 None (earliest Version on record)
2 September 20, 2018 Recruitment Status, Study Status, Outcome Measures, Contacts/Locations, Arms and Interventions, Conditions and Oversight
3 December 3, 2018 Study Status and Contacts/Locations
4 January 14, 2019 Study Status and Contacts/Locations
5 May 24, 2019 Recruitment Status, Study Status and Contacts/Locations
6 September 3, 2019 Recruitment Status, Study Status, Contacts/Locations, Eligibility, Arms and Interventions and Study Design
7 October 30, 2019 Contacts/Locations and Study Status
8 July 31, 2020 Contacts/Locations, Study Status, Outcome Measures, Arms and Interventions, Eligibility and Conditions
9 May 21, 2021 Contacts/Locations, Outcome Measures, Study Status, Eligibility and Study Design
10 October 28, 2021 Contacts/Locations and Study Status
11 January 4, 2022 Contacts/Locations and Study Status
12 March 17, 2022 Recruitment Status, Study Status, Contacts/Locations and Study Design
13 April 21, 2022 Study Status
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Study NCT03658772
Submitted Date:  September 3, 2018 (v1)

Open or close this module Study Identification
Unique Protocol ID: ARYS-001
Brief Title: Grapiprant and Pembrolizumab in Patients With Advanced or Progressive MSS Colorectal Cancer
Official Title: 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)
Secondary IDs: Keynote-878 [Merck Sharp & Dohme Corp.]
Open or close this module Study Status
Record Verification: September 2018
Overall Status: Not yet recruiting
Study Start: September 30, 2018
Primary Completion: August 2020 [Anticipated]
Study Completion: August 2020 [Anticipated]
First Submitted: August 24, 2018
First Submitted that
Met QC Criteria:
September 3, 2018
First Posted: September 5, 2018 [Actual]
Last Update Submitted that
Met QC Criteria:
September 3, 2018
Last Update Posted: September 5, 2018 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Arrys Therapeutics
Responsible Party: Sponsor
Collaborators: Merck Sharp & Dohme LLC
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
Brief Summary: 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.
Detailed Description:
Open or close this module Conditions
Conditions: Microsatellite Stable Colorectal Cancer
Keywords: Keynote-878
ARY-007
immuneoncology
checkpoint inhibitor
EP4
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Single Group Assignment
Cohort 1 to be enrolled before Cohort 2
Number of Arms: 2
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 25 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Cohort 1
Single Agent run-in with grapiprant and Combination treatment of grapiprant and pembrolizumab.
Drug: grapiprant
Cohort 1 will be treated for 1 week with oral grapiprant as a single agent, followed by 21-day combination treatment cycles of oral grapiprant in combination with IV pembolizumab.
Other Names:
  • ARYS-007
Drug: grapiprant and pembrolizumab
Cohort 2 will be administered 21-day combination treatment cycles of oral grapiprant in combination with IV pembolizumab.
Other Names:
  • ARYS-007, MK3475
  • KEYNOTE-878
Experimental: Cohort 2
Participants will be treated with grapiprant in combination with pembrolizumab.
Drug: grapiprant and pembrolizumab
Cohort 2 will be administered 21-day combination treatment cycles of oral grapiprant in combination with IV pembolizumab.
Other Names:
  • ARYS-007, MK3475
  • KEYNOTE-878
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Safety and tolerability of grapiprant alone and in combination with pembrolizumab
[ Time Frame: 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
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. Pharmacokinetics of grapiprant: Tmax
[ Time Frame: 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) ]

First time to reach maximum [peak] observed plasma concentration
4. PK of grapiprant: AUC0-Last
[ Time Frame: 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) ]

Area under the plasma concentration- time curve from time 0 to the end of the dosing interval (AUC0-last)
5. Plasma decay half-life (t1/2)
[ Time Frame: 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) ]

Measurement of half-life of grapiprant after dosing
6. Apparent oral clearance (CL/F)
[ Time Frame: 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) ]

Rate of elimination of the drug from plasma after oral administration inistration
7. Peak to trough ratio
[ Time Frame: 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) ]

Measure how drug effect is sustained over dose interval
8. Observed accumulation ratio
[ Time Frame: 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) ]

Relationship between the dosing interval and the rate of elimination for the drug.
Secondary Outcome Measures:
1. Overall Response Rate (ORR)
[ Time Frame: 7 months ]

Proportion of participants who achieved PR or better during the study per RECIST 1.1
2. Duration of Response (DR)
[ Time Frame: 7 months ]

Time when criteria for response are met, to the first documentation of relapse or progression
3. Progression -free survival (PFS)
[ Time Frame: Up to 12 months ]

Participants who discontinue treatment without disease progression
4. Disease control rate
[ Time Frame: 7 months ]

Percentage of partipcants who achieved a CR, PR and stable disease
5. 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. If no documentation of death at time of the analysis will be censored as of the date last know to be alive, or the data cutoff date, whichever is earlier.
6. Duration of treatment (DOT)
[ Time Frame: 7 months ]

Disease response for time of duration on treatment
7. Pharmacodynamic immune effects in paired tumor biopsies
[ Time Frame: predose through cycle 3 (each cycle is 21 days) ]

Assess changes in tumor infiltrating helper T cells, cytotoxic T cells and regulatory monocyte/macrophages with study drug treatment
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Key Inclusion Criteria:

  • 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 1.
  • Be able to swallow and absorb oral tablets.
  • Adequate organ function.

Key Exclusion Criteria:

  • 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.
  • History of severe hypersensitivity reactions to chimeric or humanized antibodies.
  • 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 Hepatitis C virus infection.
  • Clinically significant (i.e. active) cardiovascular disease
  • Medical conditions requiring concomitant administration of strong CYP3A4 or P glycoprotein inhibitors or inducers.
Open or close this module Contacts/Locations
Central Contact Person: Janine McDermott
Telephone: 781-392-5556
Email: Janine.mcdermott@arrystherapeutics.com
Study Officials: Jeffrey Ecsedy
Study Director
Arrys Therapeutics
Jason Sager, MD
Study Director
Arrys Therapeutics
Locations: United States, Arizona
Mayo Clinic Cancer Center - Scottsdale
Phoenix, Arizona, United States, 85054
Contact:Contact: Mayo Clinical Trials Office 855-776-0015
United States, Colorado
University of Colorado Denver-Anschutz Medical Campus
Aurora, Colorado, United States, 80045
Contact:Contact: Elizabeth Freas elizabeth.freas@ucdenver.edu
United States, Tennessee
Sarah Cannon Research Institute, LLC (SCRI)
Nashville, Tennessee, United States, 37203
Contact:Contact: Lisa Morris Lisa.MorrisLaperriere@SarahCannon.com
United States, Texas
New Experimental Therapeutics of San Antonio-NEXT Oncology
San Antonio, Texas, United States, 78240
Contact:Contact: Sarah Gomez sgomez@nextsat.com
Open or close this module IPDSharing
Plan to Share IPD: Undecided
Open or close this module References
Links:
Available IPD/Information:

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