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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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.

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

Intervention / Treatment
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* Drug: GR-MD-02
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2 mg/kg GR-MD-02<br>2 mg/kg GR-MD-02 in combination with standard pembrolizumab treatment. | Drug: GR-MD-02<br>* Patients will receive five doses of GR-MD-02 intravenously over 85 Days.<br>* Other names: Galactoarabino-rhamnogalactouronate;Drug: Pembrolizumab<br>* Patients will receive five 200mg doses of pembrolizumab intravenously over 85 days. After 85 days, patients may continue to receive pembrolizumab every 3 weeks if clinical benefit is noted.<br>* Other names: Keytruda;|
| Experimental: 4 mg/kg GR-MD-02<br>4 mg/kg GR-MD-02 in combination with standard pembrolizumab treatment. | Drug: GR-MD-02<br>* Patients will receive five doses of GR-MD-02 intravenously over 85 Days.<br>* Other names: Galactoarabino-rhamnogalactouronate;Drug: Pembrolizumab<br>* Patients will receive five 200mg doses of pembrolizumab intravenously over 85 days. After 85 days, patients may continue to receive pembrolizumab every 3 weeks if clinical benefit is noted.<br>* Other names: Keytruda;|
| Experimental: 8 mg/kg GR-MD-02<br>8 mg/kg GR-MD-02 in combination with standard pembrolizumab treatment. | Drug: GR-MD-02<br>* Patients will receive five doses of GR-MD-02 intravenously over 85 Days.<br>* Other names: Galactoarabino-rhamnogalactouronate;Drug: Pembrolizumab<br>* Patients will receive five 200mg doses of pembrolizumab intravenously over 85 days. After 85 days, patients may continue to receive pembrolizumab every 3 weeks if clinical benefit is noted.<br>* Other names: Keytruda;|
| Experimental: 4 mg/kg GR-MD-02 17 Cycles Maximum<br>4 mg/kg GR-MD-02 in combination with standard pembrolizumab treatment up to a maximum of 17 cycles. | Drug: GR-MD-02<br>* Patients will receive five doses of GR-MD-02 intravenously over 85 Days.<br>* Other names: Galactoarabino-rhamnogalactouronate;Drug: Pembrolizumab<br>* Patients will receive five 200mg doses of pembrolizumab intravenously over 85 days. After 85 days, patients may continue to receive pembrolizumab every 3 weeks if clinical benefit is noted.<br>* Other names: Keytruda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and Severity of Treatment-Related Adverse Events Measured by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | 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. | 85 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure the response rate to combined therapy with GR-MD-02 and pembrolizumab in patients. | Patients will have PET and CT scans at baseline and after 85 days to assess response to treatment. | Baseline and at Day 85 | 
| Assess the biological activity of GR-MD-02 in combination with pembrolizumab. | 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 | 85 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic, Keytruda, pembrolizumab, GR-MD-02, Galactoarabino-rhamnogalacturonate, Immunotherapy