Description:
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.
Title
- Brief Title: GR-MD-02 + Pembrolizumab Versus Pembrolizumab Monotherapy in Melanoma and Squamous Cell Head and Neck Cancer Patients
- 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
Clinical Trial IDs
- ORG STUDY ID:
2020000655
- NCT ID:
NCT04987996
Conditions
- Metastatic Melanoma
- Head and Neck Squamous Cell Carcinoma
Interventions
Drug | Synonyms | Arms |
---|
GR-MD-02 | Galactoarabino-rhamnogalactouronate | GR-MD-02 + pembrolizumab |
Placebo | | Pembrolizumab Monotherapy |
Pembrolizumab | Keytruda | GR-MD-02 + pembrolizumab |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
GR-MD-02 + pembrolizumab | Experimental | 4 mg/kg GR-MD-02 in combination with standard pembrolizumab treatment. | |
Pembrolizumab Monotherapy | Placebo Comparator | 4 mg/kg placebo in combination with standard pembrolizumab treatment. | |
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 0-2.
- 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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | 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. |
Safety Issue: | |
Description: | Determine the objective response of GR-MD-02 + pembrolizumab versus pembrolizumab monotherapy in patients with advanced MM or HNSCC |
Secondary Outcome Measures
Measure: | Evaluation of GAL-3 expression |
Time Frame: | Screening and Day 68 |
Safety Issue: | |
Description: | Compare GAL-3 expression in paired biopsies after GR-MD-02 + pembrolizumab or pembrolizumab monotherapy. |
Measure: | Evaluation of predictive biomarker |
Time Frame: | Day 85 |
Safety Issue: | |
Description: | Characterize MDSC expression over time as a predictive biomarker of response after GRMD02 + pembrolizumab or pembrolizumab monotherapy |
Measure: | Frequency of Immune-mediated adverse events |
Time Frame: | From time of informed consent to week 63 |
Safety Issue: | |
Description: | Compare the frequency of immune-mediated adverse events after GR-MD-02 + pembrolizumab versus pembrolizumab + placebo |
Measure: | Evaluation of antiviral immunity |
Time Frame: | Day 85 |
Safety Issue: | |
Description: | 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+/-). |
Measure: | Evaluation of antiviral immunity |
Time Frame: | Day 85 |
Safety Issue: | |
Description: | 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+). |
Measure: | Evaluation of antiviral immunity |
Time Frame: | Day 85 |
Safety Issue: | |
Description: | 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. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Not yet recruiting |
Lead Sponsor: | Providence Health & Services |
Trial Keywords
- HNSCC
- MM
- pembrolizumab
- GR-MD-02
- Galectin Inhibitor
- GRMD-02
- GRMD002
Last Updated
August 3, 2021