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

NCT ID: NCT03696212

Last Updated: 2021-02-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-08
• Study Completion Date: 2021-02-15

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.

Conditions

Non-small Cell Lung Cancer Adenocarcinoma

Study Design

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

Study Groups

grapiprant and pembrolizumab combination

Participants will be treated with grapiprant in combination with pembrolizumab.

Group Type: EXPERIMENTAL

grapiprant and pembrolizumab

Intervention Type: DRUG

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

Interventions

grapiprant and pembrolizumab

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

Intervention Type: DRUG

Other Intervention Names

ARYS-007; MK-3475; KEYNOTE-888; IK-007

Eligibility Criteria

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

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

• 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

Jason Sager, MD

Role: STUDY_DIRECTOR

Arrys Therapeutics

Locations

Stanford University Medical Center

Stanford, California, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

START Midwest

Grand Rapids, Michigan, United States

University of Pennsylvania Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Virginia Cancer Specialists

Fairfax, Virginia, United States

Countries

United States

Other Identifiers

KEYNOTE-888

Identifier Type: OTHER

Identifier Source: secondary_id

ARYS-002

Identifier Type: -

Identifier Source: org_study_id