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

NCT ID: NCT03658772

Last Updated: 2023-10-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-20
• Study Completion Date: 2023-03-07

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.

Conditions

Microsatellite Stable Colorectal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

Single Agent run-in with grapiprant and then combination treatment of grapiprant and pembrolizumab.

Group Type: EXPERIMENTAL

grapiprant

Intervention Type: DRUG

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 pembrolizumab.

grapiprant and pembrolizumab

Intervention Type: DRUG

Cohort 2 will be administered 21-day combination treatment cycles of oral grapiprant in combination with IV pembrolizumab.

Cohort 2

Participants will be treated with grapiprant in combination with pembrolizumab.

Group Type: EXPERIMENTAL

grapiprant and pembrolizumab

Intervention Type: DRUG

Cohort 2 will be administered 21-day combination treatment cycles of oral grapiprant in combination with IV pembrolizumab.

Interventions

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 pembrolizumab.

Intervention Type: DRUG

grapiprant and pembrolizumab

Cohort 2 will be administered 21-day combination treatment cycles of oral grapiprant in combination with IV pembrolizumab.

Intervention Type: DRUG

Other Intervention Names

ARYS-007; IK-007; ARYS-007, MK3475; KEYNOTE-878; IK-007

Eligibility Criteria

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.
• Adequate organ function.
• Able to swallow and absorb oral tablets.

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 and aspirin products within 3 days (preferably 7 days) before treatment initiation or at anytime during the study unless used for management of AE.
• History of severe hypersensitivity reactions to chimeric or humanized antibodies
• Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to treatment, or 5 half-lives, whichever is shorter.
• 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 active Hepatitis C virus infection.
• Clinically significant (i.e. active) cardiovascular disease
• Allogeneic tissue/solid organ transplant
• Medical conditions requiring concomitant administration of strong CYP3A4 or P glycoprotein inhibitors or inducers.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Arrys Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sergio Santillana, MD

Role: STUDY_DIRECTOR

Ikena Oncology

Sergio Santillana, MD

Role: STUDY_CHAIR

Ikena Oncology

Locations

Mayo Clinic Cancer Center - Scottsdale

Phoenix, Arizona, United States

University of Colorado Denver-Anschutz Medical Campus

Aurora, Colorado, United States

Sarah Cannon Research Institute, LLC (SCRI)

Nashville, Tennessee, United States

New Experimental Therapeutics of San Antonio-NEXT Oncology

San Antonio, Texas, United States

Countries

United States

References

Wang D, Cabalag CS, Clemons NJ, DuBois RN. Cyclooxygenases and Prostaglandins in Tumor Immunology and Microenvironment of Gastrointestinal Cancer. Gastroenterology. 2021 Dec;161(6):1813-1829. doi: 10.1053/j.gastro.2021.09.059. Epub 2021 Oct 2.

Reference Type: DERIVED

PMID: 34606846 (View on PubMed)

Other Identifiers

Keynote-878

Identifier Type: OTHER

Identifier Source: secondary_id

ARYS-001

Identifier Type: -

Identifier Source: org_study_id