Clinical Trials /

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

NCT02475213

Description:

The purpose of this study is to evaluate the safety of enoblituzumab (MGA271) in combination with Keytruda (pembrolizumab) when given to patients with B7-H3-expressing melanoma, squamous cell carcinoma of the head and neck (SCCHN), non small cell lung cancer (NSCLC), Urothelial Cancer and other B7-H3 expressing cancers. The study will also evaluate what is the highest dose of enoblituzumab that can be given safely when given with pembrolizumab. 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 pembrolizumab.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Melanoma
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

Title

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

    NCT ID: NCT02475213

    ORG ID: CP-MGA271-03

    Trial Conditions

    Melanoma

    Head and Neck Cancer

    Non Small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    The purpose of this study is to evaluate the safety of MGA271 in combination with Keytruda
    (pembrolizumab) when given to patients with B7-H3-expressing melanoma, squamous cell
    carcinoma of the head and neck (SCCHN) or squamous cell non small cell lung cancer (NSCLC).
    The study will also evaluate what is the highest dose of MGA271 that can be given safely
    when given with pembrolizumab. 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 pembrolizumab.

    Detailed Description

    This study is a Phase 1 open-label, dose escalation, cohort expansion, and efficacy
    follow-up study of MGA271 administered intravenously (IV) on a weekly schedule for up to 51
    doses in combination with IV pembrolizumab administered on an every-3-week schedule for up
    to 17 doses.

    The dose escalation phase is designed to characterize the safety and tolerability of the
    combination of MGA271 and pembrolizumab and to define the maximum tolerated or maximum
    administered dose (MTD/MAD). Only patients with melanoma will be enrolled in this study
    phase.

    In 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. Pre- and on-study biopsies are required
    for melanoma patients in the cohort expansion phase.

    The efficacy follow-up period consists of the 2-year period after the final dose of study
    drug.

    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 pembrolizumab Experimental MGA271: Fc-optimized, humanized monoclonal antibody. Pembrolizumab: Keytruda; human programmed death receptor-1 (PD-1)-blocking antibody approved by the US Food and Drug Administration for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor.

    Eligibility Criteria

    Inclusion Criteria:

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

    - Melanoma that has progressed during or following at least 1 and up to 5 prior
    systemic treatments for unresectable locally advanced or metastatic disease, or
    melanoma patients who are intolerable of or have refused standard first line cancer
    therapy. Pre- and on-study biopsy required.

    - SCCHN that has progressed during or following at least 1 and up to 5 prior systemic
    treatments for metastatic or recurrent disease deemed to be incurable. Patient who
    refuse radical resection for recurrent disease or are intolerant of or refused
    standard first line therapy are eligible to enroll

    - Squamous cell NSCLC that has progressed during or following 1 - 5 prior systemic
    therapies for unresectable locally advanced or metastatic disease (at least one
    docetaxel, gemcitabine, or platinum analogue based therapy), or are intolerant of or
    refused standard first line cancer therapy.

    - Measurable disease per RECIST 1.1 criteria

    - Easter Cooperative Oncology Group (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 such as vitiligo,
    resolved chilhood atopic dermatitis, psoriasis not requiring systemic therapy within
    the past 2 years, patients with history of Grave's disease that are now euthyroid
    clinically and by lab testing

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

    - Treatment with systemic cancer therapy or investigational therapy within 4 weeks of
    first study drug administration; radiation within 2 weeks; corticosteroids (greater
    than or equal to 10 mg prednisone or equivalent per day) or other immune suppressive
    drugs within 2 weeks of first study drug administration

    - Trauma or major surgery within 4 weeks of first study drug administration

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

    - Active viral, bacterial, or systemic fungal infection requiring parenteral treatment
    within 7 days of first study drug administration

    - Known history of hepatitis B or C infection or known positive test for hepatitis B
    surface antigen or core antigen, or hepatitis C polymerase chain reaction (PCR)

    - Known positive testing for human immunodeficiency virus or history of acquired immune
    deficiency syndrome

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

    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

    Squamous cell non small cell lung cancer