Phase 1/1b Study to Evaluate the Safety and Tolerability of Ciforadenant Alone and in Combination With Atezolizumab in Advanced Cancers

• ClinicalTrials.gov Identifier: NCT02655822
• Recruitment Status: Completed
• First Posted: January 14, 2016
• Last Update Posted: August 30, 2021
• Sponsor: Corvus Pharmaceuticals, Inc.
• Collaborator: Genentech, Inc.
• Information provided by (Responsible Party): Corvus Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: January 8, 2016
• First Posted Date: January 14, 2016
• Last Update Posted Date: August 30, 2021
• Study Start Date: January 2016
• Actual Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 23, 2019)

• Incidence of dose-limiting toxicities (DLTs) of ciforadenant as a single agent and in combination with atezolizumab [ Time Frame: 28 days following first administration of ciforadenant ]
• Objective response rate per RECIST v1.1 criteria of ciforadenant as a single agent and in combination with atezolizumab [ Time Frame: From start of treatment to end of treatment, up to 72 months ]
• Incidence of treatment-emergent adverse events, as assessed by NCI CTCAE v.4.03, of ciforadenant as a single agent and in combination with atezolizumab [ Time Frame: Continuously, up to 72 months ]
• Mean and median Area under the curve (AUC) of ciforadenant [ Time Frame: Up to 12 months ]
• Mean and median Maximum concentration (Cmax) of ciforadenant [ Time Frame: Up to 12 months ]
• Identify the MDL (maximum dose level) of single agent ciforadenant [ Time Frame: From start of treatment to end of treatment, up to 72 months. ]

Original Primary Outcome Measures (submitted: January 13, 2016)

• Incidence of dose-limiting toxicities (DLTs) of CPI-444 as a single agent and in combination with atezolizumab [ Time Frame: 28 days following first administration of CPI-444 ]
• Objective response rate per RECIST v1.1 criteria of CPI-444 as a single agent and in combination with atezolizumab [ Time Frame: From start of treatment to end of treatment, up to 24 months ]
• Incidence of treatment-emergent adverse events, as assessed by NCI CTCAE v.4.03, of CPI-444 as a single agent and in combination with atezolizumab [ Time Frame: Continuously, up to 24 months ]
• Mean and median Area under the curve (AUC) of CPI-444 [ Time Frame: Day 14 of Cycle 1 ]
• Mean and median Maximum concentration (Cmax) of CPI-444 [ Time Frame: Day 14 of Cycle 1 ]

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

Descriptive Information

• Brief Title: Phase 1/1b Study to Evaluate the Safety and Tolerability of Ciforadenant Alone and in Combination With Atezolizumab in Advanced Cancers
• Official Title: A Phase 1/1b, Open-Label, Multicenter, Repeat-Dose, Dose-Selection Study of Ciforadenant as Single Agent and in Combination With Atezolizumab in Patients With Selected Incurable Cancers
• Brief Summary: This is a phase 1/1b open-label, multicenter, dose-selection study of ciforadenant, an oral small molecule targeting the adenosine-A2A receptor on T-lymphocytes and other cells of the immune system. This trial will study the safety, tolerability, and anti-tumor activity of ciforadenant as a single agent and in combination with atezolizumab, a PD-L1 inhibitor against various solid tumors. Ciforadenant blocks adenosine from binding to the A2A receptor. Adenosine suppresses the anti-tumor activity of T cells and other immune cells.
• Detailed Description: This is a phase 1/1b open-label, multicenter, dose-selection study of ciforadenant, an oral small molecule targeting the adenosine-A2A receptor on T-lymphocytes and other cells of the immune system. This trial will study the safety, tolerability, and anti-tumor activity of ciforadenant as a single agent and in combination with atezolizumab, an intravenous PD-L1 inhibitor. Ciforadenant blocks adenosine from binding to the A2A receptor. Adenosine suppresses the anti-tumor activity of T cells and other immune cells.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Renal Cell Cancer
• Metastatic Castration Resistant Prostate Cancer

Intervention

• Drug: Ciforadenant
  100 mg orally twice daily for the first 14 days of each 28-day cycle.
• Drug: Ciforadenant
  100 mg orally twice daily for 28 days of each 28-day cycle.
• Drug: Ciforadenant
  200 mg orally once daily for the first 14 days of each 28-day cycle.
• Drug: Ciforadenant + atezolizumab
  Ciforadenant 100 mg orally twice daily in combination with atezolizumab intravenously.
• Drug: Ciforadenant
  Start with 150mg orally twice daily for 28-day cycles; then, increase increments by 100mg/day for 6 dose levels.

Study Arms

• Experimental: Cohort 1 - Closed
  Ciforadenant
  Intervention: Drug: Ciforadenant
• Experimental: Cohort 2 - Closed
  Ciforadenant
  Intervention: Drug: Ciforadenant
• Experimental: Cohort 3 - Closed
  Ciforadenant
  Intervention: Drug: Ciforadenant
• Experimental: Cohort 4
  Ciforadenant + atezolizumab
  Intervention: Drug: Ciforadenant + atezolizumab
• Experimental: Cohort 5 - Closed
  Ciforadenant
  Intervention: Drug: Ciforadenant

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 27, 2021): 502
• Original Estimated Enrollment (submitted: January 13, 2016): 534
• Actual Study Completion Date: July 2021
• Actual Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Renal Cell Carcinoma Inclusion Criteria

1. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
2. Documented pathologic diagnosis of clear cell RCC.
3. Relapsed or refractory to 1-2 prior lines of therapy containing at least an anti-PD-(L)1 agent.
4. Measurable disease according to RECIST v1.1
5. Mandatory newly collected tumor biopsy sample obtained prior to treatment initiation.

Renal Cell Carcinoma Exclusion Criteria

1. History of severe hypersensitivity reaction to monoclonal antibodies.
2. Has immunodeficiency or requires treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressant medication during study treatment.
3. Has an active autoimmune disease requiring systemic treatment with in the past 2 years OR a documented history of clinically severe autoimmune disease.

Metastatic Castration-Resistant Prostate Cancer Inclusion Criteria

1. Documentation of disease: progressive CRPC with histologically or cytologically confirmed adenocarcinoma of the prostate.

2. Patients must have radiologically evident metastatic disease, but it can be measurable or non-measurable disease:

   • Measurable disease: nodal, visceral, or extra nodal lesions according to RECIST v1.1 using a diagnostic computed tomography
   • Non-measurable disease: bone only disease (up to 1/3 of study population) per PCWG3 criteria
3. 1-3 prior lines of therapy, including at least one newer generation androgen synthesis inhibitor (e.g., abiraterone) or androgen receptor antagonist (e.g., enzalutamide, apalutamide, darolutamide).
4. Mandatory newly collected tumor biopsy sample obtained prior to treatment initiation.
5. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.

Metastatic Castration-Resistant Prostate Cancer Exclusion Criteria

1. Has pure small-cell histology and variants with predominant (≥ 50%) neuroendocrine differentiation.
2. Has a history of severe hypersensitivity reaction to monoclonal antibodies.
3. Has immunodeficiency or requires treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressant medication during study treatment.
4. Has an active autoimmune disease requiring systemic treatment with in the past 2 years OR a documented history of clinically severe autoimmune disease.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, United States

Administrative Information

• NCT Number: NCT02655822
• Other Study ID Numbers: CPI-444-001
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Corvus Pharmaceuticals, Inc.
• Study Sponsor: Corvus Pharmaceuticals, Inc.
• Collaborators: Genentech, Inc.

Investigators

• Study Director: Mehrdad Mobasher, MD, MPH; Corvus Pharmaceuticals

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