CPI-006 Alone and in Combination With Ciforadenant and With Pembrolizumab for Patients With Advanced Cancers

• CPI-006 (Drug): Subjects will receive escalating doses of CPI-006 administered intravenously once every 21 days until MTD is reached or until disease progression.
• CPI-006 + ciforadenant (Drug): Subjects will receive escalating doses of CPI-006 administered intravenously once every 21 days in combination with CPI-444 orally twice daily until MTD is reached for CPI-006 or until disease progression.
• CPI-006 + pembrolizumab (Drug): Subjects will receive escalating doses of CPI-006 in combination with pembrolizumab administered intravenously once every 21 days until MTD is reached for CPI-006 or until disease progression.
• CPI-006 (Drug): Selected dose of CPI-006 administered intravenously once every 21 days until disease progression.
• CPI-006 + ciforadenant (Drug): Selected dose of CPI-006 administered intravenously once every 21 days, in combination with CPI-444 orally twice daily until disease progression.
• CPI-006 + pembrolizumab (Drug): Selected dose of CPI-006 in combination with pembrolizumab administered intravenously once every 21 days until disease progression.

Primary outcomes

• Incidence of dose-limiting toxicities (DLTs) of CPI-006 as a single agent and in combination with ciforadenant and with pembrolizumab. [From start of treatment to end of treatment, up to 36 months]
• Incidence of treatment-emergent adverse events as assessed by NCI CTCAE v.4.03, of CPI-006 as single agent and in combination with ciforadenant and with pembrolizumab. [From start of treatment to end of treatment, up to 36 months]
• Identify the MDL(maximum dose level) of single agent CPI-006 [From start of treatment to end of treatment, up to 36 months]

Secondary outcomes

• Area under the curve (AUC) of CPI-006 [Day 1, 2, 8 , and 15 of Cycle 1 & 4 (each cycle is 21 days).]
• Maximum serum concentration (Cmax) of CPI-006 [Day 1, 2, 8 , and 15 of Cycle 1 & 4 (each cycle is 21 days).]
• Objective response rate per RECIST v.1.1 criteria of CPI-006 as single agent and in combination with ciforadenant and with pembrolizumab. [From start of treatment to end of treatment, up to 36 months]

Sex: All, ages: 18 Years to any

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.

• Results publication: Miller RA, Luke JJ, Hu S, Mahabhashyam S, Jones WB, Marron T, Merchan JR, Hughes BGM, Willingham SB. Anti-CD73 antibody activates human B cells, enhances humoral responses and induces redistribution of B cells in patients with cancer. J Immunother Cancer. 2022 Dec;10(12):e005802. doi: 10.1136/jitc-2022-005802. PMID 36600561

• S Mahabhashyam, MD, Study chair, Corvus Pharmaceuticals