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
Overview
- Phase
- Phase 2
- Intervention
- GR-MD-02
- Conditions
- Metastatic Melanoma
- Sponsor
- Providence Health & Services
- Locations
- 1
- Primary Endpoint
- Overall response rate based on disease imaging
- Status
- Withdrawn
- Last Updated
- 2 years ago
Overview
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.
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.
Investigators
Eligibility 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-
- •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
Arms & Interventions
GR-MD-02 + pembrolizumab
4 mg/kg GR-MD-02 in combination with standard pembrolizumab treatment.
Intervention: GR-MD-02
GR-MD-02 + pembrolizumab
4 mg/kg GR-MD-02 in combination with standard pembrolizumab treatment.
Intervention: Pembrolizumab
Pembrolizumab Monotherapy
4 mg/kg placebo in combination with standard pembrolizumab treatment.
Intervention: Placebo
Pembrolizumab Monotherapy
4 mg/kg placebo in combination with standard pembrolizumab treatment.
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
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 Outcomes
- Evaluation of predictive biomarker(Day 85)
- Evaluation of GAL-3 expression(Screening and Day 68)
- Frequency of Immune-mediated adverse events(From time of informed consent to week 63)
- Evaluation of antiviral immunity(Day 85)