Clinical Trials /

Safety Study of Enoblituzumab (MGA271) in Combination With Pembrolizumab or MGA012 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. Safety and efficacy of enoblituzumab in combination with MGA012 (anti-PD-1 monoclonal antibody; also known as INCMGA00012) will also be evaluated.

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

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety Study of Enoblituzumab (MGA271) in Combination With Pembrolizumab or MGA012 in Refractory Cancer
  • Official Title: A Phase 1, Open-Label, Dose Escalation Study of MGA271 in Combination With Pembrolizumab and in Combination With MGA012 in Patients With Melanoma, Squamous Cell Cancer of the Head and Neck, Non-Small Cell Lung Cancer, Urothelial Cancer, and Other Cancers

Clinical Trial IDs

  • ORG STUDY ID: CP-MGA271-03
  • NCT ID: NCT02475213

Conditions

  • Melanoma
  • Head and Neck Cancer
  • Non Small Cell Lung Cancer
  • Urethelial Carcinoma

Interventions

DrugSynonymsArms
EnoblituzumabMGA271enoblituzumab plus pembrolizumab
PembrolizumabKeytrudaenoblituzumab plus pembrolizumab
MGA012INCMGA00012enoblituzumb plus MGA012

Purpose

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. Safety and efficacy of enoblituzumab in combination with MGA012 (anti-PD-1 monoclonal antibody; also known as INCMGA00012) will also be evaluated.

Detailed Description

      This study is a Phase 1 open-label, dose escalation, cohort expansion, and efficacy follow-up
      study of enoblituzumab 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 enoblituzumab and pembrolizumab and to define the maximum tolerated or maximum
      administered dose (MTD/MAD). Patients with methothelioma, urethelial cancer, NSCLC, SCCHN,
      clear cell renal cell carcinoma (ccRCC), ovarian cancer, melanoma, thyroid cancer, triple
      negative breast cancer (TBNC), pancreatic cancer, colon cancer, soft tissue sarcoma, or
      prostate cancer will be enrolled in this study phase. An additional dose escalation cohort of
      up to 15 patients is designed to characterize the safety and tolerability of the combination
      of enoblituzumab and MGA012 in patients with melanoma, SCCHN, NSCLC, urothelial cancer, and
      other cancers, and any dose level not exceeding the MTD may be expanded to further evaluate
      safety and efficacy of this combination.

      During the Cohort Expansion Phase, additional cohorts of patients with B7-H3 expressing
      unresectable, locally-advanced or metastatic melanoma (up to n=16), 2 cohorts of NSCLC (n= up
      to 20 in each cohort), 2 cohorts of SCCHN (up to n=20 in each cohort) or urothelial cancer
      (up to n=16) will be enrolled to receive MGA271 in combination with pembrolizumab at the MTD
      (or MAD) established from the Dose Escalation Phase of the study.

      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

NameTypeDescriptionInterventions
enoblituzumab plus pembrolizumabExperimentalEnoblituzumab: 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, or with advanced (metastatic) non-small cell lung cancer (NSCLC) whose disease has progressed after other treatments and with tumors that express a protein called PD-L1. Keytruda is approved for use with a companion diagnostic, the PD-L1 IHC 22C3 pharmDx test, the first test designed to detect PD-L1 expression in non-small cell lung tumors.
  • Enoblituzumab
  • Pembrolizumab
enoblituzumb plus MGA012ExperimentalEnoblituzumab: Fc-optimized, humanized monoclonal antibody. MGA012: anti-PD-1 monoclonal antibody.
  • Enoblituzumab
  • MGA012

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically-proven, unresectable, locally advanced or metastatic melanoma, SCCHN,
             NSCLC, and other cancers 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 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

          -  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 cancer therapy. For squamous cell carcinoma, or adenocarcinoma without known
             activating mutation: the prior systemic therapy is at least one platinum analogue. For
             adenocarcinoma with known activating driver mutation: the prior systemic therapy is at
             least TKI directed

          -  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.

          -  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.
      
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:one 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 pembrolizumab
Measure:Number of participants that develop anti-drug antibodies
Time Frame:One year
Safety Issue:
Description:Proportion of patients who develop anti-MGA271 antibodies, immunogenicity
Measure:Change in tumor volume
Time Frame:Weeks 6, 15, 24, 33, 42, 51
Safety Issue:
Description:Anti-tumor activity of MGA271 in combination with pembrolizumab and in combination with MGA012 using both conventional RECIST 1.1 and immune-related RECIST criteria.

Details

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

Trial Keywords

  • Melanoma, Non small cell lung cancer, SCCHN
  • Other B7-H3 expressing cancers

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