Clinical trial NCT02575404: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Melanoma
Non-Small Cell Lung Cancer
Squamous Cell Carcinoma of the Head and Neck
Keywords: Metastatic
Keytruda
pembrolizumab
GR-MD-02
Galactoarabino-rhamnogalacturonate
Immunotherapy
Lead sponsor: Providence Health & Services
Sponsor class: OTHER
Collaborators: name: Galectin Therapeutics Inc.
First posted: 2015-10-14
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Primary outcomes:
measure: Frequency and Severity of Treatment-Related Adverse Events Measured by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
timeFrame: 85 Days
Secondary outcomes:
measure: Measure the response rate to combined therapy with GR-MD-02 and pembrolizumab in patients.
timeFrame: Baseline and at Day 85
measure: Assess the biological activity of GR-MD-02 in combination with pembrolizumab.
timeFrame: 85 Days
Other outcomes:
Locations:
city: Portland
country: United States
facility: Providence Cancer Center
state: Oregon
Study officials:
affiliation: Providence Health & Services
name: Brendan Curti, MD
role: PRINCIPAL_INVESTIGATOR
References: