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

• Status: Terminated
• Trial end date: 2021-02-15
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Arrys Therapeutics
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Pembrolizumab

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