Patient case: 72-year-old male with lung adenocarcinoma; genetic feature: EZR-ROS1 fusion

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

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.


Eligibility: 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
  Key Exclusion Criteria:
  -  Current use of NSAIDs, COX-2 inhibitors
  -  Known epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS gene alteration, BRAF gene mutation
  -  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
  -  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, Hepatitis B, or active Hepatitis C virus infection
  -  Clinically significant (i.e.active) cardiovascular disease

Relevance to patient case: not relevant