Grapiprant (ARY-007) and Pembrolizumab in Patients With Advanced or Metastatic Post-PD-1/L1 NSCLC Adenocarcinoma
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03696212 |
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Recruitment Status :
Terminated
(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.)
First Posted : October 4, 2018
Last Update Posted : February 21, 2021
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Sponsor:
Arrys Therapeutics
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Arrys Therapeutics
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Brief 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 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Non-small Cell Lung Cancer Adenocarcinoma | Drug: grapiprant and pembrolizumab | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 18 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | January 8, 2019 |
| Actual Primary Completion Date : | February 15, 2021 |
| Actual Study Completion Date : | February 15, 2021 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Lung cancer
| Arm | Intervention/treatment |
|---|---|
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Experimental: grapiprant and pembrolizumab combination
Participants will be treated with grapiprant in combination with pembrolizumab.
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Drug: grapiprant and pembrolizumab
Participants will be administered 21-day cycles of oral grapiprant in combination with IV pembrolizumab
Other Names:
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Primary Outcome Measures :
- Safety and tolerability of grapiprant in combination with pembrolizumab [ Time Frame: Up to 90 days after the end of treatment (average of 7 months) ]Number of incidence, severity, relationship, concomitant medications administered, and duration of treatment emergent adverse events using CTCAE v5.0
- Define the recommended phase 2 dose (RP2D) of grapiprant combined with pembrolizumab [ Time Frame: Through Cycle 1 (21 days) ]Number, incidence and severity of treatment related adverse events as assessed by CTCAE 5.0
- Objective response rate (ORR) [ Time Frame: 7 months ]Proportion of participants who achieved PR or better during the study per RECIST 1.1 and iRECIST
Secondary Outcome Measures :
- Progression-free survival (PFS) [ Time Frame: Up to 12 months ]Participants who discontinue treatment without disease progression
- Overall survival (OS) [ Time Frame: Up to 2 years from start of study drug ]Date of study drug to date of death due to any cause
- Duration of treatment (DoT) [ Time Frame: 7 months ]Disease response for time of duration on treatment
- Disease control rate (DCR) [ Time Frame: 7 months ]Percentage of patients who have achieved CR, PR and stable disease
- Duration of response (DoR) [ Time Frame: Up to 12 months ]Time from documentation of tumor response to disease progression per RECIST and iRECIST 1.1
- PK of grapiprant: AUC [ Time Frame: 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). ]Area under the plasma concentration-time curve
- PK of grapiprant: Cmax [ Time Frame: 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). ]Peak serum concentration of grapiprant
- Plasma decay half-life (t1/2) [ Time Frame: 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). ]Measurement of half-life of grapiprant after dosing
- Apparent oral clearance (CL/F) [ Time Frame: 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). ]Rate of elimination of the drug from plasma after oral administration
- Peak to trough ratio [ Time Frame: 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). ]Measure how drug effect is sustained over dose interval
- Observed accumulation ratio [ Time Frame: 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). ]Relationship between the dosing interval and the rate of elimination for the drug
- Pharmacodynamic immune effects in paired tumor biopsies [ Time Frame: Predose through cycle 3 (each cycle is 21 days) ]Asses changes in tumor infiltrating helper T cells, cytoxic T cells and regulatory monocyte/macrophages with study treatment
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Key Inclusion Criteria:
- 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
- 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
Key Exclusion Criteria:
- 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
- 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03696212
Locations
| United States, California | |
| Stanford University Medical Center | |
| Stanford, California, United States, 94305 | |
| United States, Michigan | |
| Barbara Ann Karmanos Cancer Institute | |
| Detroit, Michigan, United States, 48201 | |
| START Midwest | |
| Grand Rapids, Michigan, United States, 49546 | |
| United States, Pennsylvania | |
| University of Pennsylvania Abramson Cancer Center | |
| Philadelphia, Pennsylvania, United States, 19104 | |
| Fox Chase Cancer Center | |
| Philadelphia, Pennsylvania, United States, 19111 | |
| United States, Virginia | |
| Virginia Cancer Specialists | |
| Fairfax, Virginia, United States, 22031 | |
Sponsors and Collaborators
Arrys Therapeutics
Merck Sharp & Dohme Corp.
Investigators
| Study Director: | Jason Sager, MD | Arrys Therapeutics |
| Responsible Party: | Arrys Therapeutics |
| ClinicalTrials.gov Identifier: | NCT03696212 |
| Other Study ID Numbers: |
ARYS-002 KEYNOTE-888 ( Other Identifier: MERCK ) |
| First Posted: | October 4, 2018 Key Record Dates |
| Last Update Posted: | February 21, 2021 |
| Last Verified: | February 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Lung Neoplasms Carcinoma, Non-Small-Cell Lung Adenocarcinoma Adenocarcinoma of Lung Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases |
Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Pembrolizumab Antineoplastic Agents, Immunological Antineoplastic Agents |