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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Metastatic Melanoma; Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: GR-MD-02; Drug: Pembrolizumab; Drug: Placebo

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97213
      • Portland Providence Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: Galactoarabino-rhamnogalactouronate; Drug: Pembrolizumab; Patients will receive 200mg doses of pembrolizumab intravenously over 85 Days.; Other Names: Keytruda
Placebo Comparator: Pembrolizumab Monotherapy; 4 mg/kg placebo in combination with standard pembrolizumab treatment.	Drug: Pembrolizumab; Patients will receive 200mg doses of pembrolizumab intravenously over 85 Days.; Other Names: Keytruda; Drug: Placebo; Patients will receive up to seventeen doses of placebo intravenously over 85 Days.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of GAL-3 expression	Compare GAL-3 expression in paired biopsies after GR-MD-02 + pembrolizumab or pembrolizumab monotherapy.	Screening and Day 68
Evaluation of predictive biomarker	Characterize MDSC expression over time as a predictive biomarker of response after GRMD02 + pembrolizumab or pembrolizumab monotherapy	Day 85
Frequency of Immune-mediated adverse events	Compare the frequency of immune-mediated adverse events after GR-MD-02 + pembrolizumab versus pembrolizumab + placebo	From time of informed consent to week 63
Evaluation of antiviral immunity	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+/-).	Day 85
Evaluation of antiviral immunity	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+).	Day 85
Evaluation of antiviral immunity	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.	Day 85

Collaborators and Investigators

• Sponsor: Providence Health & Services
• Collaborators: Providence Cancer Center, Earle A. Chiles Research Institute
• Investigators: Principal Investigator: Brendan D. Curti, MD, Providence Health & Services

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2031

Study Registration Dates

• First Submitted: July 14, 2021
• First Submitted That Met QC Criteria: July 23, 2021
• First Posted (Actual): August 3, 2021

Study Record Updates

• Last Update Posted (Actual): June 6, 2023
• Last Update Submitted That Met QC Criteria: June 2, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: HNSCC; MM; pembrolizumab; GR-MD-02; Galectin Inhibitor; GRMD-02; GRMD002
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Neoplasms, Squamous Cell; Carcinoma; Melanoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: 2020000655

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No