Clinical Trials /

Safety Study of Enoblituzumab (MGA271) in Combination With Ipilimumab in Refractory Cancer

NCT02381314

Description:

The purpose of this study is to evaluate the safety of enoblituzumab (MGA271) in combination with Yervoy (ipilimumab) when given to patients with B7-H3-expressing melanoma, squamous cell carcinoma of the head and neck (SCCHN), non small cell lung cancer (NSCLC) and other B7-H3 expressing cancers. The study will also evaluate what is the best dose of enoblituzumab to use when given with ipilimumab. Assessments will also be done to see how the drug acts in the body (pharmacokinetics (PK), pharmacodynamics) and to evaluate potential anti-tumor activity of enoblituzumab in combination with ipilimumab.

Related Conditions:
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Thyroid Gland Neoplasm
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Pancreatic Carcinoma
  • Peritoneal Mesothelioma
  • Pleural Mesothelioma
  • Prostate Carcinoma
  • Renal Cell Carcinoma
  • Soft Tissue Sarcoma
  • Urothelial Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Safety Study of MGA271 in Combination With <span class="go-doc-concept go-doc-intervention">Ipilimumab</span> in Refractory Cancer

Title

  • Brief Title: Safety Study of MGA271 in Combination With Ipilimumab in Refractory Cancer
  • Official Title: A Phase 1, Open-Label, Dose Escalation Study of MGA271 in Combination With Ipilimumab in Patients With B7-H3-Expressing Melanoma, Squamous Cell Cancer of the Head and Neck, Non Small Cell Lung Cancer, and Other B7H3 Expressing Cancers
  • Clinical Trial IDs

    NCT ID: NCT02381314

    ORG ID: CP-MGA271-02

    Trial Conditions

    Melanoma

    Head and Neck Cancer

    Non Small Cell Lung Cancer

    Mesothelioma

    Urothelial Carcinoma

    Clear Cell Renal Cell Carcinoma

    Ovarian Cancer

    Thyroid Cancer

    Triple Negative Breast Cancer

    Pancreatic Cancer

    Colon Cancer

    Soft Tissue Sarcoma

    Prostate Cancer

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    The purpose of this study is to evaluate the safety of MGA271 in combination with Yervoy
    (ipilimumab) when given to patients with B7-H3-expressing melanoma, squamous cell carcinoma
    of the head and neck (SCCHN), non small cell lung cancer (NSCLC) and other B7H3 expressing
    cancers. The study will also evaluate what is the best dose of MGA271 to use when given with
    ipilimumab. Assessments will also be done to see how the drug acts in the body
    (pharmacokinetics (PK), pharmacodynamics) and to evaluate potential anti-tumor activity of
    MGA271 in combination with ipilimumab.

    Detailed Description

    This study is a Phase 1 open-label, dose escalation, and cohort expansion study of MGA271
    administered intravenously (IV) on a weekly schedule for up to 51 doses in combination with
    IV ipilimumab administered on an every-3-week schedule for 4 doses.

    The dose escalation phase is designed to characterize the safety and tolerability of the
    combination of MGA271 and ipilimumab and to define the maximum tolerated or administered
    dose (MTD/MAD) in patients with B7-H3 expressing mesothelioma, urothelial cancer, NSCLC,
    SCCHN, Clear cell renal cell carcinoma (ccRCC), ovarian cancer, melanoma, thyroid cancer,
    Triple negative breast cancer (TNBC), pancreatic cancer, colon cancer, soft tissue sarcoma,
    or prostate cancer.

    The cohort expansion phase, 3 cohorts of 16 patients each will be enrolled to further
    evaluate the safety and potential efficacy of the combination administered at the MTD/MAD
    dose in patients with melanoma, NSCLC, and SCCHN.

    All tumor evaluations will be carried out by both Response Evaluation Criteria in Solid
    Tumors (RECIST) and immune-related response criteria (irRC).

    Trial Arms

    Name Type Description Interventions
    MGA271 plus ipilimumab Experimental MGA271: Fc-optimized, humanized monoclonal antibody. Ipilimumab: Yervoy; recombinant, fully humanized IgG-1 CTLA-4 blocking antibody approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of unresectable or metastatic melanoma.

    Eligibility Criteria

    Inclusion Criteria:

    - Histologically-proven, unresectable, locally advanced or metastatic melanoma, SCCHN,
    or NSCLC that express B7-H3.

    - Melanoma that has progressed within 90 days with progression on a checkpoint
    inhibitor (e.g., anti-PD-L1, anti-PD-1, anti-CTLA-4) as the most recent prior therapy

    - SCHNN or NSCLC that has progressed during or following 1 - 5 prior systemic regimens

    - Mesothelioma that has progressed during or following at least 1 and up to 3 prior
    systemic treatments for unresectable locally advanced or metastatic disease. The
    prior systemic chemotherapy must have included a pemetrexed (anti-folate)-based
    regimen in combination with platinum agent. For patients in whom pemetrexed was
    contraindicated or not tolerated or not an approved therapy (e.g., peritoneal
    mesothelioma), prior therapy with a first-line platinum-based regimen is required.

    - Urothelial cancer arising in the bladder, renal pelvis, ureter or urethra that has
    progressed during or following at least 1 and up to 5 prior systemic treatments for
    unresectable locally advanced or metastatic disease (includes anti-PD-L1,anti-PD-1,
    but excludes other experimental therapies). Patients must have received at least one
    platinum-containing regimen (e.g., gemcitabine/cisplatin [GC], dose-dense
    methotrexate/vinblastine/doxorubicin/cisplatin [DDMVAC], or
    carboplatinum/gemcitabine). No more than 5 prior systemic regimens allowed.

    - Thyroid cancer that has progressed during or following at least 1 and up to 5 prior
    chemotherapy regimen(s). Prior therapy excludes experimental therapies given in Phase
    1 trials.

    - Pancreatic cancer that has progressed during or following at least 1 and up to 3
    prior chemotherapy regimens. Prior therapy excludes experimental therapies given in
    Phase 1 trials.

    - Ovarian cancer that has progressed during or following at least 2 and up to 4 prior
    therapeutic regimens (e.g., 2 prior platinum containing regimens or if platinum
    resistant, a liposomal doxorubicin or topotecan containing regimen). Prior therapy
    excludes experimental therapies given in Phase 1 trials

    - Colon cancer that has progressed during or following at least 2 and up to 4 prior
    therapeutic regimens (e.g., fluoropyrimidine and/or irinotecan and/or oxaliplatin
    and/or anti-EGFR antibody containing regimens). Prior therapy excludes experimental
    therapies given in Phase 1 trials.

    - Prostate cancer that has progressed during or following at least 1 and up to 5 prior
    therapeutic regimens (e.g., abiraterone, enzalutamide, docetaxel). Prior therapy
    excludes experimental therapies given in Phase 1 trials.

    - Soft tissue sarcoma that has progressed during or following at least 1 and up to 5
    prior therapeutic regimens. Prior therapy excludes experimental therapies given in
    Phase 1 trials.

    - TNBC that has progressed during or following at least 1 and up to 5 prior therapeutic
    regimens. Prior therapy excludes experimental therapies given in Phase 1 trials.

    - ccRCC that has progressed during or following at least 1 and up to 5 prior
    therapeutic regimens. Prior therapy excludes experimental therapies given in Phase 1
    trials.

    - Measurable disease per RECIST 1.1 criteria

    - ECOG performance status 0 or 1

    - Acceptable laboratory parameters and adequate organ reserve.

    Exclusion Criteria:

    - Patients with a history of symptomatic central nervous system metastases, unless
    treated and asymptomatic

    - Patients with history of autoimmune disease with certain exceptions

    - History of allogeneic bone marrow, stem cell, or solid organ transplant

    - Treatment with systemic cancer therapy or investigational therapy within 4 weeks;
    radiation within 2 weeks; trauma or major surgery within 4 weeks

    - History of clinically-significant cardiovascular disease; gastrointestinal
    perforation; gastrointestinal bleeding, acute pancreatitis or diverticulitis within 4
    weeks;

    - Active viral, bacterial, or systemic fungal infection requiring parenteral treatment
    within 7 days; positive for human immunodeficiency virus or AIDS, hepatitis B or C.

    - Known hypersensitivity to recombinant proteins, polysorbate 80, or any excipient
    contained in the drug or vehicle formulation for MGA271 or ipilimumab.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Number of participants with adverse events

    Secondary Outcome Measures

    Peak plasma concentration

    Number of participants that develop anti-drug antibodies

    Change in tumor volume

    Trial Keywords

    B7-H3-expressing neoplasms