Clinical Trials /

A Study to Assess the Safety and Tolerability of Atezolizumab in Combination With Other Immune-Modulating Therapies in Participants With Locally Advanced or Metastatic Solid Tumors

NCT02174172

Description:

This global, multicenter, open-label study will evaluate the safety and tolerability of atezolizumab in combination with other immune-modulating therapies in the treatment of selected advanced or metastatic malignancies. The atezolizumab plus ipilimumab arm (Arm A) will focus primarily on participants with advanced or metastatic non-small cell lung cancer (NSCLC). The atezolizumab plus interferon alfa-2b arm (Arm B), plus pegylated interferon alfa-2a (PEG−interferon alfa-2a, Arm C), and atezolizumab plus PEG-interferon Alfa-2a plus bevacizumab (Arm D) will enroll participants with advanced or metastatic renal cell carcinoma (RCC), metastatic NSCLC and melanoma. The atezolizumab plus obinutuzumab) (Arm E) will enroll participants with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Atezolizumab will be administered as intravenous (IV) infusion every 3 weeks (q3w).

Related Conditions:
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Renal Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

A Study to Assess the Safety and Tolerability of <span class="go-doc-concept go-doc-intervention">MPDL3280A</span> in Combination With Other Immune-modulating Therapies in Patients With Locally Advanced or Metastatic Solid Tumors

Title

  • Brief Title: A Study to Assess the Safety and Tolerability of MPDL3280A in Combination With Other Immune-modulating Therapies in Patients With Locally Advanced or Metastatic Solid Tumors
  • Official Title: A PHASE I STUDY OF THE SAFETY AND PHARMACOLOGY OF MPDL3280A ADMINISTERED WITH IPILIMUMAB OR INTERFERON-ALPHA IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC SOLID TUMORS
  • Clinical Trial IDs

    NCT ID: NCT02174172

    ORG ID: GO29322

    NCI ID: 2014-000812-33

    Trial Conditions

    Solid Cancers

    Trial Interventions

    Drug Synonyms Arms
    Interferon alfa-2b Arm B: MPDL3280A + interferon alfa-2b
    Ipilimumab Arm A: MPDL3280A + ipilimumab
    MPDL3280A Arm A: MPDL3280A + ipilimumab, Arm B: MPDL3280A + interferon alfa-2b

    Trial Purpose

    This global, multicenter, open-label study will evaluate the safety and tolerability of
    MPDL3280A in combination with other immune-modulating therapies in the treatment of selected
    advanced or metastatic malignancies. The MPDL3280A plus ipilimumab arm (Arm A) will focus
    primarily on patients with advanced or metastatic NSCLC. The MPDL3280A plus interferon
    alfa-2b arm (Arm B) will enroll patients with advanced or metastatic RCC and melanoma.
    MPDL3280A will be administered intravenously every 3 weeks (q3w).

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Arm A: MPDL3280A + ipilimumab Experimental Ipilimumab, MPDL3280A
    Arm B: MPDL3280A + interferon alfa-2b Experimental Interferon alfa-2b, MPDL3280A

    Eligibility Criteria

    Inclusion Criteria:

    - Age >/= 18 years

    - Histologically or cytologically documented locally advanced or metastatic solid
    tumors meeting the following study drug-specific criteria:

    Inclusion criteria specific to Arm A: MPDL3280A + ipilimumab

    - Escalation stage: NSCLC patients

    - Expansion stage: NSCLC patients

    - Mandatory biopsy cohort: NSCLC or melanoma patients

    - Prior MPDL3280A-treated cohort: NSCLC or melanoma patients

    Inclusion criteria specific to Arm B: MPDL3280A + interferon alfa-2b

    - Escalation stage: RCC or melanoma patients

    - Expansion stage: RCC or melanoma patients

    - Mandatory biopsy cohort: RCC or melanoma patients

    - Prior MPDL3280A-treated cohort: RCC or melanoma patients

    Inclusion criteria specific to prior MPDL3280A-treated cohorts

    Patients who have previously received MPDL3280A as monotherapy or in combination with
    other agents (except those outlined as exclusions) are eligible if they meet the following
    criteria:

    - Radiologic evidence of progression after having derived stable disease, partial
    response, or complete response; patients without evidence of clinical benefit may be
    enrolled only after approval by the Medical Monitor.

    - Minimum of 21 days from the last dose of MPDL3280A

    - No permanent discontinuation of MPDL3280A due to a treatment-related adverse event

    - Recovery from all MPDL3280A-related adverse events to Grade </= 1 or baseline at the
    time of consent

    - No history of Grade >/= 3 immune-related adverse events from MPDL3280A, of Grade >/=
    3 elevated total bilirubin, of usage of additional immunosuppression or ongoing use
    of > 10 mg prednisone or corticosteroid dose-equivalent.

    - Disease progression during or after at least one previous systemic, anti-cancer
    treatment for locally advanced or metastatic NSCLC and RCC

    - Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

    - Life expectancy >/= 12 weeks

    - Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors
    (RECIST) v1.1

    - Adequate hematologic and end organ function as confirmed by laboratory results within
    14 days prior to the first study treatment

    - For women who are not postmenopausal or surgically sterile and for men with partners
    of childbearing potential, the agreement to remain abstinent or to use single or
    combined contraceptive methods that result in a failure rate of <1% per year during
    the treatment period and for at least 6 months after the last dose of study drug.

    Exclusion Criteria:

    General Medical Exclusions:

    - Pregnant and lactating women

    - Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within
    3 weeks prior to initiation of study treatment, with the following exception: (1)
    hormone-replacement therapy or oral contraceptives; (2) tyrosine kinase inhibitors
    (TKIs) that have been discontinued > 7 days prior to Cycle 1, Day 1, baseline scans
    must be obtained after discontinuation of prior TKIs

    - Investigational therapy within 28 days prior to initiation of study treatment

    - History of severe allergic, anaphylactic, or other hypersensitivity reactions to
    chimeric or humanized antibodies or fusion proteins

    - Known hypersensitivity or allergy to Chinese hamster ovary cell products or any
    component of the MPDL3280A formulation

    - History of or active autoimmune disease

    - History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced
    pneumonitis, organizing pneumonia, risk of pulmonary toxicity, or evidence of active
    pneumonitis on screening chest computed tomography (CT) scan

    - Prior allogeneic bone marrow transplantation or prior solid organ transplantation

    - History of human immunodeficiency virus (HIV)

    - Patients with active hepatitis B

    - Patients with active hepatitis C

    - Patients with active tuberculosis

    - Any serious medical condition, physical examination finding, or abnormality in
    clinical laboratory tests that, in the investigator's judgment, precludes the
    patient's safe participation in and completion of the study

    Cancer-Specific Exclusions:

    - NSCLC with sensitizing mutations in EGFR or ALK rearrangements

    - Melanoma with BRAF mutations

    - Active or untreated central nervous system (CNS) metastases, as determined by CT or
    MRI evaluation during screening and prior radiographic assessments

    - Spinal cord compression not definitively treated with surgery and/or radiation or
    previously diagnosed and treated spinal cord compression without evidence that
    disease has been clinically stable for >/= 2 weeks prior to screening

    - Leptomeningeal disease

    - Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
    drainage procedures (once monthly or more frequently); patients with indwelling
    catheters are allowed.

    - Uncontrolled/unstable tumor-related pain

    - Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of
    bisphosphonate therapy or denosumab

    - History of other malignancy within 2 years prior to screening, except for
    appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma,
    Stage I uterine cancer, localized prostate cancer treated with curative intent,
    ductal carcinoma in situ treated surgically with curative intent, or other cancers
    with a similar outcome

    Exclusion Criteria Related to Medications:

    - Prior treatment with CD137 agonists or immune checkpoint blockade therapies (Note:
    Patients who enroll in the prior MPDL3280A-treated cohorts will have previously
    received MPDL3280A)

    - Treatment with systemic immunostimulatory agents within four weeks or five half-lives
    of the drug, whichever is shorter, prior to Cycle 1, Day 1

    - Treatment with systemic immunosuppressive medications within 2 weeks prior to Cycle
    1, Day 1 (the use of inhaled corticosteroids and mineralocorticoids is allowed)

    Exclusion Criteria Specific to Arm B (MPDL3280A + Interferon Alfa-2b):

    - History of depression, suicidal ideation or behavior, bipolar disorder, or psychosis

    - Hypersensitivity to interferon alpha or any component of the product

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Incidence of dose-limiting toxicities (DLTs)

    Incidence of adverse events (AEs)

    Secondary Outcome Measures

    Best overall response, as determined by investigator assessment using conventional RECIST v1.1 and modified RECIST criteria

    Duration of objective response

    Overall survival

    Progression-free survival

    Objective response (partial response plus complete response), confirmed by repeat assessments >/= 4 weeks after initial documentation and determined by investigator assessment using conventional RECIST v1.1 and modified RECIST criteria

    Serum concentrations of study drugs, MPDL3280A and ipilimumab administered in combination

    Serum concentrations of study drugs, MPDL3280A and interferon alfa-2b administered in combination

    Trial Keywords