grapiprant (ary-007) and pembrolizumab in patients with advanced or metastatic post-pd-1/l1 nsclc adenocarcinoma

Conditions: Non-small Cell Lung Cancer 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 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