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Microsatellite Stable Colorectal CancerPhase 1NCT03658772

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

A Phase 1 study testing grapiprant and grapiprant and pembrolizumab in people with Microsatellite Stable Colorectal Cancer, run by Arrys Therapeutics at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Microsatellite Stable Colorectal Cancer
What is being tested?
grapiprant and grapiprant and pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
4 sitesUnited States
Study dates
20 Sep 2018to 7 Mar 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  • Adequate organ function.
  • Able to swallow and absorb oral tablets.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • University of Colorado Denver-Anschutz Medical Campus

    Aurora, Colorado, 80045

  • Sarah Cannon Research Institute, LLC (SCRI)

    Nashville, Tennessee, 37203

  • Mayo Clinic Cancer Center - Scottsdale

    Phoenix, Arizona, 85054

  • New Experimental Therapeutics of San Antonio-NEXT Oncology

    San Antonio, Texas, 78240

Other trials in United States

About this study

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)

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.

Being tested
grapiprant, grapiprant and pembrolizumab
Keywords
Keynote-878, ARY-007, Immuno-Oncology, checkpoint inhibitor, EP4, IK-007

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • grapiprantDrug

    Also called ARYS-007, IK-007

    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 pembrolizumabDrug

    Also called ARYS-007, MK3475, KEYNOTE-878, IK-007

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

Study groups in NCT03658772
Study groupRoleWhat they receive
Cohort 1ExperimentalSingle Agent run-in with grapiprant and then combination treatment of grapiprant and pembrolizumab.
Receives: Drug: grapiprant; Drug: grapiprant and pembrolizumab
Cohort 2ExperimentalParticipants will be treated with grapiprant in combination with pembrolizumab.
Receives: Drug: grapiprant and pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

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

  2. 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

    Measured: Through Cycle 1 (21 days)

Secondary outcomes (15)

  1. Overall Response Rate (ORR)

    Proportion of participants who achieved PR or better during the study per RECIST 1.1

    Measured: 7 months

  2. Duration of Response (DOR)

    Time when criteria for response are met, to the first documentation of relapse or progression

    Measured: 7 months

  3. Progression -free survival (PFS)

    Participants who discontinue treatment without disease progression

    Measured: Up to 12 months

  4. Disease control rate (DCR)

    Percentage of participants who achieved a CR, PR and stable disease

    Measured: 7 months

  5. Overall survival (OS)

    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 known to be alive, or the data cutoff date, whichever is earlier.

    Measured: Up to 2 years from start of study drug.

  6. Duration of treatment (DOT)

    Time of duration on treatment

    Measured: 7 months

  7. Serum tumor marker changes

    Assess changes in serum tumor markers including but not limited to carcinoembryonic antigen (CEA), when appropriate (eg. CA-19.9, CA125, and lactate dehyrogenase (LDH)) with disease response.

    Measured: 7 months

  8. Pharmacodynamic immune effects in paired tumor biopsies

    Assess changes in tumor infiltrating helper T cells, cytotoxic T cells and regulatory monocyte/macrophages with study drug treatment

    Measured: predose through cycle 3 (each cycle is 21 days)

  9. PGEM as a pharmacodynamic and predictive biomarker

    Evaluate disease response in all evaluable participants and in those with a positive initial assessment of Urine prostaglandin E2 metabolite (PGEM)

    Measured: PreScreening through 7 months

  10. PK of grapiprant: Tmax

    First time to reach maximum [peak] observed plasma concentration

    Measured: 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)

  11. PK of grapiprant: AUC0 last

    Area under the plasma concentration time curve from time 0 to the end of the dosing interval (AUC0 last)

    Measured: 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).

  12. Plasma decay half-life (t1/2)

    Measurement of half-life of grapiprant after dosing

    Measured: 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)

  13. Apparent oral clearance (CL/F)

    Rate of elimination of the drug from plasma after oral administration

    Measured: 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)

  14. Peak to trough ratio

    Measure how drug effect is sustained over dose interval

    Measured: 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)

  15. Observed accumulation ratio

    Relationship between the dosing interval and the rate of elimination for the drug.

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Sep 2018
  2. Study start20 Sep 2018
  3. Primary completion7 Mar 2023
  4. Study completion7 Mar 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Model description
Cohort 1 to be enrolled before Cohort 2
Masking
None (open label)
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03658772
Sponsor's protocol ID
ARYS-001
Other IDs
Keynote-878
Status last verified
Oct 2023
First submitted
24 Aug 2018
Last updated
24 Oct 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 34606846

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing grapiprant and grapiprant and pembrolizumab in people with Microsatellite Stable Colorectal Cancer, run by Arrys Therapeutics at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03658772, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2023.

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