Grapiprant and Pembrolizumab in Patients With Advanced or Progressive MSS Colorectal Cancer

Key Inclusion Criteria:

• Male and female adult patients 18 years of age or older on day of signing informed consent.
• Patients must have a histologically confirmed advanced, metastatic, or progressive Microsatellite Stable (MSS) Colorectal Cancer (CRC) per institutional standards.
• Patient has received at least two prior lines of therapy for advanced or metastatic CRC, at least one of which included fluorouracil.
• Highly effective birth control.
• Measurable disease.
• Accessible tumor that can be safely accessed for multiple core biopsies and patient is willing to provide tissue from newly obtain biopsies before and during treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Adequate organ function.
• Able to swallow and absorb oral tablets.

Key Exclusion Criteria:

• Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
• Current use of NSAIDs, COX-2 inhibitors and aspirin products within 3 days (preferably 7 days) before treatment initiation or at anytime during the study unless used for management of AE.
• History of severe hypersensitivity reactions to chimeric or humanized antibodies
• Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to treatment, or 5 half-lives, whichever is shorter.
• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
• Known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Known active CNS metastases and/or carcinomatous meningitis.
• Active autoimmune disease that has required systemic treatment in past 2 years.
• History of non-infectious pneumonitis that required steroids or has current pneumonitis.
• Active infection requiring systemic therapy.
• Recent (within the last 12 months) 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
• Allogeneic tissue/solid organ transplant
• Medical conditions requiring concomitant administration of strong CYP3A4 or P glycoprotein inhibitors or inducers.