Clinical Trials /

GR-MD-02 Plus Pembrolizumab in Melanoma, Non-small Cell Lung Cancer, and Squamous Cell Head and Neck Cancer Patients

NCT02575404

Description:

This study is a dose escalation of GR-MD-02 with the standard therapeutic dose of pembrolizumab in patients with advanced melanoma, non-small cell lung cancer, and head and neck squamous cell cancer.

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

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: GR-MD-02 Plus Pembrolizumab in Melanoma, Non-small Cell Lung Cancer, and Squamous Cell Head and Neck Cancer Patients
  • Official Title: Phase IB Study of a Galectin Inhibitor (GR-MD-02) and Pembrolizumab in Patients With Metastatic Melanoma, Non-Small Cell Lung Cancer, and Head and Neck Squamous Cell Carcinoma.

Clinical Trial IDs

  • ORG STUDY ID: 15-166
  • NCT ID: NCT02575404

Conditions

  • Melanoma
  • Non-Small Cell Lung Cancer
  • Squamous Cell Carcinoma of the Head and Neck

Interventions

DrugSynonymsArms
GR-MD-02Galactoarabino-rhamnogalactouronate2 mg/kg GR-MD-02
PembrolizumabKeytruda2 mg/kg GR-MD-02

Purpose

This study is a dose escalation of GR-MD-02 with the standard therapeutic dose of pembrolizumab in patients with advanced melanoma, non-small cell lung cancer, and head and neck squamous cell cancer.

Detailed Description

      This study will employ a 3+3 phase I design with dose escalation of GR-MD-02 in conjunction
      with the standard therapeutic dose of pembrolizumab in patients with advanced melanoma who
      have had progression after ipilimumab and/or BRAF targeted therapy when a BRAF mutation is
      present, non-small cell lung cancer patients with disease progression after targeted therapy,
      or head and neck squamous cell carcinoma patients with disease progression after at least one
      platinum-containing regimen.

      In addition to monitoring for toxicity and clinical response, blood and tumor samples will be
      obtained to assess immunologic measures relevant to galectin biology and pembrolizumab T-cell
      checkpoint inhibition.
    

Trial Arms

NameTypeDescriptionInterventions
2 mg/kg GR-MD-02Experimental2 mg/kg GR-MD-02 in combination with standard pembrolizumab treatment.
  • GR-MD-02
  • Pembrolizumab
4 mg/kg GR-MD-02Experimental4 mg/kg GR-MD-02 in combination with standard pembrolizumab treatment.
  • GR-MD-02
  • Pembrolizumab
8 mg/kg GR-MD-02Experimental8 mg/kg GR-MD-02 in combination with standard pembrolizumab treatment.
  • GR-MD-02
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with metastatic or unresectable melanoma for whom treatment with
             pembrolizumab is indicated. Histological confirmation of melanoma will be required by
             previous biopsy or cytology.

          -  Patients with non-small cell lung cancer for whom treatment with pembrolizumab is
             indicated.

          -  Patients with squamous cell carcinoma of the head and neck for whom treatment with
             pembrolizumab is indicated

          -  Patients who have radiographic progression using Response Evaluation Criteria In Solid
             Tumors (RECIST) currently on pembrolizumab are also eligible.

          -  Patients must be ≥ 18 years of age.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

          -  Women of childbearing potential must have a serum or urine pregnancy test performed
             within 72 hours prior to the start of protocol treatment. The results of this test
             must be negative in order for the patient to be eligible. In addition, women of
             childbearing potential as well as male patients must agree to take appropriate
             precautions to avoid pregnancy.

          -  No active bleeding.

          -  Anticipated lifespan greater than 12 weeks.

          -  Patients must sign a study-specific consent document.

        Exclusion Criteria:

          -  Patients who have previously received a galectin antagonist

          -  Patients with active autoimmune disease except for autoimmune thyroiditis or vitiligo

          -  Patients with history of colitis

          -  Patients with untreated brain metastases. Patients with treated brain metastases who
             demonstrate control of brain metastases with follow-up imaging 4 or more weeks after
             initial therapy are eligible.

          -  Other active metastatic cancer requiring treatment.

          -  Patients with active infection requiring antibiotics.

          -  Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo
             or fetus.

          -  Need for chronic steroids. Inhaled corticosteroids are acceptable.

          -  Laboratory values (to be performed within 28 days of enrollment) outside of
             protocol-specified ranges.

          -  Inability to give informed consent and comply with the protocol. Patients with a
             history of psychiatric illness must be judged able to understand fully the
             investigational nature of the study and the risks associated with the therapy.

          -  Any medical condition that in the opinion of the Principal Investigator would
             compromise the safety or conduct of the study procedures.

          -  Unresolved immune-mediated pneumonitis, diarrhea, elevation of hepatocellular enzymes
             or other toxicities requiring greater than physiological replacement doses of
             steroids.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Frequency and Severity of Treatment-Related Adverse Events Measured by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Time Frame:85 Days
Safety Issue:
Description:Patients are seen in clinic 7 times over 85 days. At each visit, a research nurse performs a toxicity check. Patients have 5 physical exams during the 85-day period.

Secondary Outcome Measures

Measure:Measure the response rate to combined therapy with GR-MD-02 and pembrolizumab in patients.
Time Frame:Baseline and at Day 85
Safety Issue:
Description:Patients will have PET and CT scans at baseline and after 85 days to assess response to treatment.
Measure:Assess the biological activity of GR-MD-02 in combination with pembrolizumab.
Time Frame:85 Days
Safety Issue:
Description:Patients will provide 5 blood samples over 85 days to measure the absolute number of CD4+T Cells, CD8+ T cells and melanoma-specific T cells

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Providence Health & Services

Trial Keywords

  • Metastatic
  • Keytruda
  • pembrolizumab
  • GR-MD-02
  • Galactoarabino-rhamnogalacturonate
  • Immunotherapy

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