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GR-MD-02 + Pembrolizumab Versus Pembrolizumab Monotherapy in Melanoma and Squamous Cell Head and Neck Cancer Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04987996
Recruitment Status : Suspended (Study delayed due to ongoing discussions with the owner of one of the investigational agents.)
First Posted : August 3, 2021
Last Update Posted : May 9, 2022
Sponsor:
Collaborator:
Providence Cancer Center, Earle A. Chiles Research Institute
Information provided by (Responsible Party):
Providence Health & Services

Brief Summary:
The purpose of this study is to test the safety & efficacy of combination drugs versus placebo to treat metastatic melanoma and head and neck squamous cell carcinoma.

Condition or disease Intervention/treatment Phase
Metastatic Melanoma Head and Neck Squamous Cell Carcinoma Drug: GR-MD-02 Drug: Placebo Drug: Pembrolizumab Phase 2

Detailed Description:

Eligible patients will be registered, stratified by diagnosis (melanoma versus OHN cancer), and the number of prior systemic therapies, and randomized to receive either GR-MD-02 + pembrolizumab or pembrolizumab + placebo.

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 92 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Randomized Double-Blind Placebo Controlled Phase II Study of a Galectin Inhibitor (GR-MD-02) and Pembrolizumab Versus Pembrolizumab and Placebo in Patients With Metastatic Melanoma and Head and Neck Squamous Cell Carcinoma
Estimated Study Start Date : July 1, 2022
Estimated Primary Completion Date : August 1, 2026
Estimated Study Completion Date : August 1, 2030


Arm Intervention/treatment
Experimental: GR-MD-02 + pembrolizumab
4 mg/kg GR-MD-02 in combination with standard pembrolizumab treatment.
Drug: GR-MD-02
Patients will receive up to seventeen doses of GR-MD-02 intravenously over 85 Days.
Other Name: Galactoarabino-rhamnogalactouronate

Drug: Pembrolizumab
Patients will receive 200mg doses of pembrolizumab intravenously over 85 Days.
Other Name: Keytruda

Placebo Comparator: Pembrolizumab Monotherapy
4 mg/kg placebo in combination with standard pembrolizumab treatment.
Drug: Placebo
Patients will receive up to seventeen doses of placebo intravenously over 85 Days.

Drug: Pembrolizumab
Patients will receive 200mg doses of pembrolizumab intravenously over 85 Days.
Other Name: Keytruda




Primary Outcome Measures :
  1. Overall response rate based on disease imaging [ Time Frame: From date of randomization until the date of first documented progression, assessed up to 63 weeks. ]
    Determine the objective response of GR-MD-02 + pembrolizumab versus pembrolizumab monotherapy in patients with advanced MM or HNSCC


Secondary Outcome Measures :
  1. Evaluation of GAL-3 expression [ Time Frame: Screening and Day 68 ]
    Compare GAL-3 expression in paired biopsies after GR-MD-02 + pembrolizumab or pembrolizumab monotherapy.

  2. Evaluation of predictive biomarker [ Time Frame: Day 85 ]
    Characterize MDSC expression over time as a predictive biomarker of response after GRMD02 + pembrolizumab or pembrolizumab monotherapy

  3. Frequency of Immune-mediated adverse events [ Time Frame: From time of informed consent to week 63 ]
    Compare the frequency of immune-mediated adverse events after GR-MD-02 + pembrolizumab versus pembrolizumab + placebo

  4. Evaluation of antiviral immunity [ Time Frame: Day 85 ]
    Assess the biological activity of GR-MD-02 + pembrolizumab and in comparison to pembrolizumab monotherapy by measuring CD4+T cells with a memory phenotype (CD3+CD4+Ki67+CD25+FoxP3-CCR7-CD45RA-CD27+CD28+/-).

  5. Evaluation of antiviral immunity [ Time Frame: Day 85 ]
    Assess the biological activity of GR-MD-02 + pembrolizumab and in comparison to pembrolizumab monotherapy by measuring CD8+ T cells with effector phenotype (CD3+CD8+CD28-CD95+).

  6. Evaluation of antiviral immunity [ Time Frame: Day 85 ]
    Assess the biological activity of GR-MD-02 + pembrolizumab and in comparison to pembrolizumab monotherapy by measuring tumor-specific T cells using autologous and/or HLA-matched tumor when available.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with unresectable or metastatic melanoma including unknown primary, mucosal or uveal melanomas. Histological confirmation of melanoma will be required by previous biopsy or cytology. Patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression during or after platinum-containing chemotherapy are eligible. PD-L1 testing is not needed for OHN cancers.
  • Patients who have received anti-PD1 or anti-PD-L1 in the past are eligible if it has been at least 6 months since the last anti-PD-1 or PD-L1 dose, they meet all other eligibility criteria and progression of malignancy has been documented on imaging. Progression for this patient subset is defined as the appearance of one or more new metastatic sites, or a 5% or greater increase in the sum of diameter of target lesions or an unequivocal increase in non-target site. Treatment naïve melanoma patients are eligible.
  • Patients must be ≥ 18 years of age.
  • 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 (see Appendix C).
  • Patients with history of autoimmune 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.
  • Patients requiring other systemic oncologic therapy, including experimental therapies.
  • Patients with active infection requiring antibiotics.
  • Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo or fetus.
  • Need for steroids at greater than physiologic replacement doses. Inhaled corticosteroids are acceptable.
  • Laboratory exclusions (to be performed within 28 days of enrollment):

    • WBC < 3.0 x 109/L
    • Hgb < 9.0 g/dL
    • AST or ALT > 1.5 times ULN
    • Total bilirubin > 1.9 g/dL, unless due to Gilbert's Syndrome. If Gilbert's Syndrome is present by clinical history, then direct bilirubin must by < 3.0 g/dl.
    • Known history of HIV
    • Known history of Hepatitis B
    • Known history of Hepatitis C
    • INR > 1.5x ULN
  • Inability to give informed consent and comply with the protocol. Patients 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04987996


Locations
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United States, Oregon
Portland Providence Medical Center
Portland, Oregon, United States, 97213
Sponsors and Collaborators
Providence Health & Services
Providence Cancer Center, Earle A. Chiles Research Institute
Investigators
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Principal Investigator: Brendan D. Curti, MD Providence Health & Services
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Responsible Party: Providence Health & Services
ClinicalTrials.gov Identifier: NCT04987996    
Other Study ID Numbers: 2020000655
First Posted: August 3, 2021    Key Record Dates
Last Update Posted: May 9, 2022
Last Verified: May 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Providence Health & Services:
HNSCC
MM
pembrolizumab
GR-MD-02
Galectin Inhibitor
GRMD-02
GRMD002
Additional relevant MeSH terms:
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Carcinoma
Melanoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents