This is a Phase 1/1b open-label, dose escalation and dose expansion study of CPI-006, a humanized monoclonal antibody (mAb) targeting the CD73 cell-surface ectonucleotidase in adult subjects with select advanced cancers. CPI-006 will be evaluated as a single agent, in combination with ciforadenant (an oral adenosine 2A receptor antagonist), in combination with pembrolizumab (an anti-PD1 antibody), and in combination with ciforadenant and pembrolizumab.

Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
2. Documented incurable cancer with one of the following histologies: nonsmall cell lung cancer, renal cell cancer, triple negative breast cancer, colorectal cancer with microsatellite instability(MSI), bladder cancer, cervical cancer, uterine cancer, sarcoma, endometrial cancer, and metastatic castration resistant prostate cancer.
3. At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
4. For Escalation: At least 1 but not more than 5 prior systemic therapies for advanced/ recurrent or progressing disease. For Expansion: Subject must have progressed on, be refractory to, or intolerant to 1-3 prior systemic therapies.
5. Willingness to provide tumor biopsies.

Exclusion Criteria

1. History of severe hypersensitivity reaction to monoclonal antibodies.
2. Subjects who have received prior therapy with regimens containing cytotoxicT-lymphocyte antigen-4 (CTLA-4), programmed cell death ligand 1 (PDL1), or PD1 antagonists are NOT permitted to enroll unless all adverse events (AEs) while receiving prior immunotherapy have resolved to Grade 1 or baseline prior to screening.
3. History of (non-infectious) pneumonitis that required steroids or subject has current pneumonitis.
4. The use of any investigational medication or device in the 30 days prior to screening and throughout the study is prohibited.
5. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.