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

• ClinicalTrials.gov Identifier: NCT03454451
• Recruitment Status: Recruiting
• First Posted: March 6, 2018
• Last Update Posted: February 2, 2021
• Sponsor: Corvus Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Corvus Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: February 5, 2018
• First Posted Date: March 6, 2018
• Last Update Posted Date: February 2, 2021
• Actual Study Start Date: April 25, 2018
• Estimated Primary Completion Date: March 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 16, 2020)

• Incidence of dose-limiting toxicities (DLTs) of CPI-006 as a single agent and in combination with ciforadenant and with pembrolizumab. [ Time Frame: 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. [ Time Frame: From start of treatment to end of treatment, up to 36 months ]
• Identify the MDL(maximum dose level) of single agent CPI-006 [ Time Frame: From start of treatment to end of treatment, up to 36 months ]

Original Primary Outcome Measures (submitted: March 2, 2018)

• Incidence of dose-limiting toxicities (DLTs) of CPI-006 as a single agent and in combination with CPI-444 and with pembrolizumab. [ Time Frame: 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 CPI-444 and with pembrolizumab. [ Time Frame: From start of treatment to end of treatment, up to 36 months ]
• Identify the MDL(maximum dose level) of single agent CPI-006 [ Time Frame: From start of treatment to end of treatment, up to 36 months ]

Current Secondary Outcome Measures (submitted: January 16, 2020)

• Area under the curve (AUC) of CPI-006 [ Time Frame: Day 1, 2, 8 , and 15 of Cycle 1 & 4 (each cycle is 21 days). ]
• Maximum serum concentration (Cmax) of CPI-006 [ Time Frame: 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. [ Time Frame: From start of treatment to end of treatment, up to 36 months ]

Original Secondary Outcome Measures (submitted: March 2, 2018)

• Area under the curve (AUC) of CPI-006 [ Time Frame: Day 1, 2, 8 , and 15 of Cycle 1 & 4 (each cycle is 21 days). ]
• Maximum serum concentration (Cmax) of CPI-006 [ Time Frame: 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 CPI-444 and with pembrolizumab. [ Time Frame: From start of treatment to end of treatment, up to 36 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: CPI-006 Alone and in Combination With Ciforadenant and With Pembrolizumab for Patients With Advanced Cancers
• Official Title: A PHASE 1/1b MULTICENTER STUDY TO EVALUATE THE HUMANIZED ANTI-CD73 ANTIBODY, CPI-006, AS A SINGLE AGENT OR IN COMBINATION WITH CIFORADENANT, WITH PEMBROLIZUMAB, AND WITH CIFORADENANT PLUS PEMBROLIZUMAB IN ADULT SUBJECTS WITH ADVANCED CANCERS
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Non-Small Cell Lung Cancer
• Renal Cell Cancer
• Colorectal Cancer
• Triple Negative Breast Cancer
• Cervical Cancer
• Ovarian Cancer
• Pancreatic Cancer
• Endometrial Cancer
• Sarcoma
• Squamous Cell Carcinoma of the Head and Neck
• Bladder Cancer
• Metastatic Castration Resistant Prostate Cancer
• Non-hodgkin Lymphoma

Intervention

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

Study Arms

• Experimental: Cohort 1a
  CPI-006
  Intervention: Drug: CPI-006
• Experimental: Cohort1b
  CPI-006 + ciforadenant
  Intervention: Drug: CPI-006 + ciforadenant
• Experimental: Cohort 1c
  CPI-006 + pembrolizumab
  Intervention: Drug: CPI-006 + pembrolizumab
• Experimental: Cohort 2a
  CPI-006
  Intervention: Drug: CPI-006
• Experimental: Cohort 2b
  CPI-006 + ciforadenant
  Intervention: Drug: CPI-006 + ciforadenant
• Experimental: Cohort 2c
  CPI-006 + pembrolizumab
  Intervention: Drug: CPI-006 + pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 2, 2018): 378
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2023
• Estimated Primary Completion Date: March 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Listed Location Countries: Australia, United States

Administrative Information

• NCT Number: NCT03454451
• Other Study ID Numbers: CPI-006-001
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Corvus Pharmaceuticals, Inc.
• Study Sponsor: Corvus Pharmaceuticals, Inc.
• Collaborators: Not Provided

Investigators

• Study Chair: S Mahabhashyam, MD; Corvus Pharmaceuticals

• PRS Account: Corvus Pharmaceuticals, Inc.
• Verification Date: February 2021