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.
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
| Drug | Synonyms | Arms |
|---|
| GR-MD-02 | Galactoarabino-rhamnogalactouronate | 2 mg/kg GR-MD-02 |
| Pembrolizumab | Keytruda | 2 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
| Name | Type | Description | Interventions |
|---|
| 2 mg/kg GR-MD-02 | Experimental | 2 mg/kg GR-MD-02 in combination with standard pembrolizumab treatment. | |
| 4 mg/kg GR-MD-02 | Experimental | 4 mg/kg GR-MD-02 in combination with standard pembrolizumab treatment. | |
| 8 mg/kg GR-MD-02 | Experimental | 8 mg/kg GR-MD-02 in combination with standard pembrolizumab treatment. | |
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: | Active, not recruiting |
| Lead Sponsor: | Providence Health & Services |
Trial Keywords
- Metastatic
- Keytruda
- pembrolizumab
- GR-MD-02
- Galactoarabino-rhamnogalacturonate
- Immunotherapy
Last Updated
March 10, 2021
