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Phase 1/1b Study to Evaluate the Safety and Tolerability of CPI-444 Alone and in Combination With Atezolizumab in Advanced Cancers

NCT02655822

Description:

This is a phase 1/1b open-label, multicenter, dose-selection study of CPI-444, 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 CPI-444 as a single agent and in combination with atezolizumab, a PD-L1 inhibitor against various solid tumors. CPI-444 blocks adenosine from binding to the A2A receptor. Adenosine suppresses the anti-tumor activity of T cells and other immune cells.

Related Conditions:
  • Bladder Carcinoma
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Head and Neck Carcinoma
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Prostate Carcinoma
  • Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Phase 1/1b Study to Evaluate the Safety and Tolerability of CPI-444 Alone and in Combination With <span class="go-doc-concept go-doc-intervention">Atezolizumab</span> in Advanced Cancers

Title

  • Brief Title: Phase 1/1b Study to Evaluate the Safety and Tolerability of CPI-444 Alone and in Combination With Atezolizumab in Advanced Cancers
  • Official Title: A Phase 1/1b, Open-Label, Multicenter, Repeat-Dose, Dose-Selection Study of CPI-444 as Single Agent and in Combination With Atezolizumab in Patients With Selected Incurable Cancers
  • Clinical Trial IDs

    NCT ID: NCT02655822

    ORG ID: CPI-444-001

    Trial Conditions

    Non-Small Cell Lung Cancer

    Malignant Melanoma

    Renal Cell Cancer

    Triple Negative Breast Cancer

    Prostate Cancer

    Head and Neck Cancer

    Colorectal Cancer

    Bladder Cancer

    Trial Interventions

    Drug Synonyms Arms
    CPI-444 Cohort 1
    CPI-444 Cohort 2
    CPI-444 Cohort 3
    CPI-444 + atezolizumab Cohort 4

    Trial Purpose

    This is a phase 1/1b open-label, multicenter, dose-selection study of CPI-444, 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 CPI-444
    as a single agent and in combination with atezolizumab, a PD-L1 inhibitor against various
    solid tumors. CPI-444 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 CPI-444, 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 CPI-444
    as a single agent and in combination with atezolizumab, an intravenous PD-L1 inhibitor.
    CPI-444 blocks adenosine from binding to the A2A receptor. Adenosine suppresses the
    anti-tumor activity of T cells and other immune cells.

    Trial Arms

    Name Type Description Interventions
    Cohort 1 Experimental CPI-444 CPI-444
    Cohort 2 Experimental CPI-444 CPI-444
    Cohort 3 Experimental CPI-444 CPI-444
    Cohort 4 Experimental CPI-444 + atezolizumab CPI-444 + atezolizumab

    Eligibility Criteria

    Inclusion Criteria

    1. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.

    2. Documented incurable cancer with one of the following histologies: non-small cell
    lung cancer, malignant melanoma, renal cell cancer, triple negative breast cancer,
    and metastatic castration-resistant prostate cancer, head and neck cancer, colorectal
    cancer, and bladder cancer.

    3. At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST
    1.1).

    4. At least 1 but not more than 5 prior systemic therapies for advanced/recurrent or
    progressing disease.

    Exclusion Criteria

    1. History of severe hypersensitivity reaction to monoclonal antibodies.

    2. Any active autoimmune disease or a documented history of serious autoimmune disease
    within the past 5 years requiring immunosuppressive therapy.

    3. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
    pneumonitis, idiopathic pneumonitis, or clinical symptoms of active pneumonitis.

    4. The use of any investigational medication or device in the 30 days prior to screening
    and throughout the study is prohibited.

    5. If a patient is currently receiving denosumab, this must be discontinued prior to
    enrollment. Substitution with biphosphonates are acceptable.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Incidence of dose-limiting toxicities (DLTs) of CPI-444 as a single agent and in combination with atezolizumab

    Objective response rate per RECIST v1.1 criteria of CPI-444 as a single agent and in combination with atezolizumab

    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

    Mean and median Area under the curve (AUC) of CPI-444

    Mean and median Maximum concentration (Cmax) of CPI-444

    Secondary Outcome Measures

    Trial Keywords

    NSCLC

    MEL

    RCC

    TNBC

    Breast Cancer

    Metastatic Castration-Resistant Prostate Cancer

    mCRPC

    Triple Negative Breast Neoplasms

    Neoplasms

    CRC

    Lung Cancer

    Prostate Cancer

    Kidney Cancer

    Colon Cancer

    Rectal Cancer

    Skin Cancer