NCT03658772

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
54

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Sep 2018

Longer than P75 for phase_1

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 24, 2018

Completed
12 days until next milestone

First Posted

Study publicly available on registry

September 5, 2018

Completed
15 days until next milestone

Study Start

First participant enrolled

September 20, 2018

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 7, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 7, 2023

Completed
Last Updated

October 24, 2023

Status Verified

October 1, 2023

Enrollment Period

4.5 years

First QC Date

August 24, 2018

Last Update Submit

October 23, 2023

Conditions

Microsatellite Stable Colorectal Cancer

Keywords

Keynote-878ARY-007Immuno-Oncologycheckpoint inhibitorEP4IK-007

Outcome Measures

Primary Outcomes (2)

  • Safety and tolerability of grapiprant alone and in combination with pembrolizumab

    Number of incidence, severity, and duration of treatment emergent adverse events using CTCAE v5.0

    Up to 90 days after the end of treatment (average of 7 months)

  • Define the recommended phase 2 dose (RP2D) of grapiprant combined with pembrolizumab

    Number, incidence and severity of treatment related adverse events as assessed by CTCAE 5.0

    Through Cycle 1 (21 days)

Secondary Outcomes (15)

  • Overall Response Rate (ORR)

    7 months

  • Duration of Response (DOR)

    7 months

  • Progression -free survival (PFS)

    Up to 12 months

  • Disease control rate (DCR)

    7 months

  • Overall survival (OS)

    Up to 2 years from start of study drug.

  • +10 more secondary outcomes

Study Arms (2)

Cohort 1

EXPERIMENTAL

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

Drug: grapiprantDrug: grapiprant and pembrolizumab

Cohort 2

EXPERIMENTAL

Participants will be treated with grapiprant in combination with pembrolizumab.

Drug: grapiprant and pembrolizumab

Interventions

grapiprantDRUG

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.

Also known as: ARYS-007, IK-007
Cohort 1
grapiprant and pembrolizumabDRUG

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

Also known as: ARYS-007, MK3475, KEYNOTE-878, IK-007
Cohort 1Cohort 2

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Mayo Clinic Cancer Center - Scottsdale

Phoenix, Arizona, 85054, United States

Location

University of Colorado Denver-Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Sarah Cannon Research Institute, LLC (SCRI)

Nashville, Tennessee, 37203, United States

Location

New Experimental Therapeutics of San Antonio-NEXT Oncology

San Antonio, Texas, 78240, United States

Location

Related Publications (1)

  • 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.

    PMID: 34606846DERIVED

MeSH Terms

Interventions

grapiprantpembrolizumab

Study Officials

  • Sergio Santillana, MD

    Ikena Oncology

    STUDY DIRECTOR

  • Sergio Santillana, MD

    Ikena Oncology

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: Cohort 1 to be enrolled before Cohort 2
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 24, 2018

First Posted

September 5, 2018

Study Start

September 20, 2018

Primary Completion

March 7, 2023

Study Completion

March 7, 2023

Last Updated

October 24, 2023

Record last verified: 2023-10

Locations

US(4)