AzTrials
AzTrials

Non-small Cell Lung Cancer AdenocarcinomaPhase 1/2NCT03696212

Grapiprant (ARY-007) and Pembrolizumab in Patients With Advanced or Metastatic Post-PD-1/L1 NSCLC Adenocarcinoma

A Phase 1/2 study testing grapiprant and pembrolizumab in people with Non-small Cell Lung Cancer Adenocarcinoma, run by Arrys Therapeutics at 6 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This study will be conducted in adult participants diagnosed with NSCLC who have been previously treated for a minimum of 12 weeks with any PD-1 or PD-L1 checkpoint inhibitor. This is a phase 1b/2, multi-center, open label study designed to assess safety and tolerability of grapiprant in combination with… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
grapiprant and pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
6 sitesUnited States
Study dates
8 Jan 2019to 15 Feb 2021
Phase
Phase 1/2
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 at least 18 years of age on day of signing informed consent
  • Histologically confirmed non-small cell lung cancer (NSCLC) adenocarcinoma
  • Advanced (stage IIIb) disease that is not amenable to curative intent treatment with concurrent chemoradiation and metastatic (stage IV) patients
  • Progressed clinically and/or radiographically per RECIST v1.1 after receiving a PD-1 or PD-L1 antagonist for a minimum of 12 weeks
  • Measurable disease per RECIST v1.1
  • Disease that can be safely accessed via bronchoscopic, thoracoscopic or percutaneous biopsy for multiple core biopsies and participant is willing to provide tissue from newly obtain biopsies on study in a subgroup of patients
Show all 10Show fewer
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  • Adequate organ function
  • Highly effective birth control
  • Able to swallow and absorb oral tablets

Who cannot join

  • Current use of NSAIDs, COX-2 inhibitors
  • Known epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS gene alteration
  • No history of smoking (≤100 cigarettes lifetime)
  • History of severe hypersensitivity reactions to a PD-1/L1 antibody
  • Received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment or 5 half-lives, whichever is shorter
  • Received prior radiotherapy within 2 weeks of start of study treatment
Show all 18Show fewer
  • Has received a live vaccine within 30 days prior to the first dose of study treatment
  • Taking strong CYP3A4 or P-glycoprotein inhibitors or inducers
  • Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment
  • Known additional malignancy that is progressing or has required active treatment within the past 3 years (with some permitted exceptions)
  • Known active CNS metastases and/or carcinomatous meningitis
  • Active autoimmune disease that has required systemic treatment in past 2 years
  • History of pneumonitis that required steroids or has current pneumonitis
  • Has an active infection requiring systemic therapy
  • Recent or current GI ulcer, colitis or non-immune colitis
  • Known history of human immunodeficiency virus (HIV) infection, or known active Hepatitis B, or Hepatitis C virus infection
  • Has had an allogeneic tissue/solid organ transplant
  • Clinically significant (i.e.active) cardiovascular disease

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Virginia Cancer Specialists

    Fairfax, Virginia, 22031

  • START Midwest

    Grand Rapids, Michigan, 49546

  • University of Pennsylvania Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Stanford University Medical Center

    Stanford, California, 94305

Other trials in United States

About this study

Official title: Open Label, Single Arm, Phase 1b/2 Study to Evaluate the Safety and Efficacy of Grapiprant (ARY-007) in Combination With Pembrolizumab in Patients With Advanced or Metastatic Post-PD-1/L1 Non-Small Cell Lung Cancer (NSCLC) Adenocarcinoma

This study will be conducted in adult participants diagnosed with NSCLC who have been previously treated for a minimum of 12 weeks with any PD-1 or PD-L1 checkpoint inhibitor. This is a phase 1b/2, 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 disease response with grapiprant based on investigator assessments. Pharmacokinetics, pharmacodynamics and response biomarkers will also be assessed.

Being tested
grapiprant and pembrolizumab

What participants receive

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

  • grapiprant and pembrolizumabDrug

    Also called ARYS-007, MK-3475, KEYNOTE-888, IK-007

    Participants will be administered 21-day cycles of oral grapiprant in combination with IV pembrolizumab

Study groups in NCT03696212
Study groupRoleWhat they receive
grapiprant and pembrolizumab combinationExperimentalParticipants 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 in combination with pembrolizumab

    Number of incidence, severity, relationship, concomitant medications administered, 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)

  3. Objective response rate (ORR)

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

    Measured: 7 months

Secondary outcomes (12)

  1. Progression-free survival (PFS)

    Participants who discontinue treatment without disease progression

    Measured: Up to 12 months

  2. Overall survival (OS)

    Date of study drug to date of death due to any cause

    Measured: Up to 2 years from start of study drug

  3. Duration of treatment (DoT)

    Disease response for time of duration on treatment

    Measured: 7 months

  4. Disease control rate (DCR)

    Percentage of patients who have achieved CR, PR and stable disease

    Measured: 7 months

  5. Duration of response (DoR)

    Time from documentation of tumor response to disease progression per RECIST and iRECIST 1.1

    Measured: Up to 12 months

  6. PK of grapiprant: AUC

    Area under the plasma concentration-time curve

    Measured: 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).

  7. PK of grapiprant: Cmax

    Peak serum concentration of grapiprant

    Measured: 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).

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

    Measurement of half-life of grapiprant after dosing

    Measured: 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).

  9. Apparent oral clearance (CL/F)

    Rate of elimination of the drug from plasma after oral administration

    Measured: 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).

  10. Peak to trough ratio

    Measure how drug effect is sustained over dose interval

    Measured: 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. Observed accumulation ratio

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

    Measured: 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. Pharmacodynamic immune effects in paired tumor biopsies

    Asses changes in tumor infiltrating helper T cells, cytoxic T cells and regulatory monocyte/macrophages with study treatment

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

Timeline

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

  1. First posted4 Oct 2018
  2. Study start8 Jan 2019
  3. Primary completion15 Feb 2021
  4. Study completion15 Feb 2021

Why it stopped: Based on the totality of the generated combined safety and efficacy data in the interim period, the company decided to terminate the combination study in NSCLC patients. There are no subjects on study drug at this time or in the EOT Follow-up period.

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03696212
Sponsor's protocol ID
ARYS-002
Other IDs
KEYNOTE-888
Status last verified
Feb 2021
First submitted
3 Oct 2018
Last updated
21 Feb 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing grapiprant and pembrolizumab in people with Non-small Cell Lung Cancer Adenocarcinoma, run by Arrys Therapeutics at 6 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 10 inclusion and 18 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: stopped early, as of the sponsor's last update on 21 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 was stopped early (reason given: Based on the totality of the generated combined safety and efficacy data in the interim period, the company decided to terminate the combination study in NSCLC patients. There are no subjects on study drug at this time or in the EOT Follow-up period.). Results are not available in the source record.

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 in combination with pembrolizumab (time frame: Up to 90 days after the end of treatment (average of 7 months)). The study lists 3 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 NCT03696212.

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 21 Feb 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in