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

Arrys Therapeutics

Status and phase

Terminated

Phase 2

Phase 1

Conditions

Non-small Cell Lung Cancer Adenocarcinoma

Treatments

Drug: grapiprant and pembrolizumab

Study type

Interventional

Funder types

Industry

Identifiers

NCT03696212

KEYNOTE-888 (Other Identifier)

ARYS-002

Details and patient eligibility

About

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.

Enrollment

18 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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