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

Title

  • Brief Title: Safety Study of Enoblituzumab (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 Melanoma, Non-Small Cell Lung Cancer, and Other Cancers

Clinical Trial IDs

  • ORG STUDY ID: CP-MGA271-02
  • NCT ID: NCT02381314

Conditions

  • Melanoma
  • Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
enoblituzumab plus ipilimumabenoblituzumab (MGA271); ipilimumab (Yervoy)enoblituzumab plus ipilimumab

Purpose

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.

Detailed Description

      This study is a Phase 1 open-label, dose escalation, and cohort expansion study of
      enoblituzumab 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 enoblituzumab 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, 2 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 and NSCLC.

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

Trial Arms

NameTypeDescriptionInterventions
enoblituzumab plus ipilimumabExperimentalEnoblituzumab: 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.
  • enoblituzumab plus ipilimumab

Eligibility Criteria

        Inclusion Criteria - Cohort Expansion Phase:

          -  Histologically-proven, unresectable, locally advanced or metastatic melanoma or NSCLC

               -  Melanoma: Advanced or metastatic melanoma patients may be systemic therapy naïve
                  or may have received systemic treatment for unresectable locally advanced or
                  metastatic disease. A patient who previously received systemic therapy must have
                  had progression on a checkpoint inhibitor (e.g., anti-PD-L1, anti-PD-1,
                  anti-CTLA-4) as the most recent prior therapy.

               -  NSCLC: NSCLC that has progressed during or following 1 or more prior systemic
                  therapies for unresectable locally advanced or metastatic disease. Patients who
                  are intolerant of, or have refused treatment with standard first line cancer
                  therapy, will be allowed to enroll. Patients must not have had more than 5 prior
                  systemic regimens (excluding experimental therapies) for unresectable locally
                  advanced or metastatic disease.

          -  B7-H3 expression is not required for eligibility in this study; however, tumor
             expression of B7-H3 will be evaluated for all patients.

          -  Measurable disease per RECIST 1.1 criteria

          -  ECOG performance status 0 or 1

          -  Acceptable laboratory parameters and adequate organ reserve.

        Exclusion Criteria - Cohort Expansion Phase:

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with adverse events
Time Frame:1 year
Safety Issue:
Description:Adverse events, serious adverse events

Secondary Outcome Measures

Measure:Peak plasma concentration
Time Frame:7 weeks
Safety Issue:
Description:PK of MGA271 in combination with ipilimumab
Measure:Number of participants that develop anti-drug antibodies
Time Frame:7 weeks
Safety Issue:
Description:Proportion of patients who develop anti-MGA271 antibodies, immunogenicity
Measure:Change in tumor volume
Time Frame:Weeks 9, 18, 27, 39, and 51
Safety Issue:
Description:Anti-tumor activity of MGA271 in combination with ipilimumab using both conventional RECIST 1.1 and immune-related RECIST criteria.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:MacroGenics

Trial Keywords

  • Other B7-H3 expressing cancers

Last Updated

March 25, 2019