Clinical Trials /

Grapiprant and Pembrolizumab in Patients With Advanced or Progressive MSS Colorectal Cancer

NCT03658772

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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)

Clinical Trial IDs

  • ORG STUDY ID: ARYS-001
  • SECONDARY ID: Keynote-878
  • NCT ID: NCT03658772

Conditions

  • Microsatellite Stable Colorectal Cancer

Interventions

DrugSynonymsArms
grapiprantARYS-007Cohort 1
grapiprant and pembrolizumabARYS-007, MK3475, KEYNOTE-878Cohort 1

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Cohort 1ExperimentalSingle Agent run-in with grapiprant and Combination treatment of grapiprant and pembrolizumab.
  • grapiprant
  • grapiprant and pembrolizumab
Cohort 2ExperimentalParticipants will be treated with grapiprant in combination with pembrolizumab.
  • grapiprant and pembrolizumab

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)
Safety Issue:
Description:Number of incidence, severity, and duration of treatment emergent adverse events using CTCAE v5.0

Secondary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:7 months
Safety Issue:
Description:Proportion of participants who achieved PR or better during the study per RECIST 1.1
Measure:Duration of Response (DR)
Time Frame:7 months
Safety Issue:
Description:Time when criteria for response are met, to the first documentation of relapse or progression
Measure:Progression -free survival (PFS)
Time Frame:Up to 12 months
Safety Issue:
Description:Participants who discontinue treatment without disease progression
Measure:Disease control rate
Time Frame:7 months
Safety Issue:
Description:Percentage of partipcants who achieved a CR, PR and stable disease
Measure:Overall survival (OS)
Time Frame:Up to 2 years from start of study drug.
Safety Issue:
Description: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.
Measure:Duration of treatment (DOT)
Time Frame:7 months
Safety Issue:
Description:Disease response for time of duration on treatment
Measure:Pharmacodynamic immune effects in paired tumor biopsies
Time Frame:predose through cycle 3 (each cycle is 21 days)
Safety Issue:
Description:Assess changes in tumor infiltrating helper T cells, cytotoxic T cells and regulatory monocyte/macrophages with study drug treatment

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Arrys Therapeutics

Trial Keywords

  • Keynote-878
  • ARY-007
  • immuneoncology
  • checkpoint inhibitor
  • EP4

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