Clinical trial NCT04987996: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Metastatic Melanoma
Head and Neck Squamous Cell Carcinoma
Keywords: HNSCC
MM
pembrolizumab
GR-MD-02
Galectin Inhibitor
GRMD-02
GRMD002
Lead sponsor: Providence Health & Services
Sponsor class: OTHER
Collaborators: name: Providence Cancer Center, Earle A. Chiles Research Institute
First posted: 2021-08-03
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Overall response rate based on disease imaging
timeFrame: From date of randomization until the date of first documented progression, assessed up to 63 weeks.
Secondary outcomes:
measure: Evaluation of GAL-3 expression
timeFrame: Screening and Day 68
measure: Evaluation of predictive biomarker
timeFrame: Day 85
measure: Frequency of Immune-mediated adverse events
timeFrame: From time of informed consent to week 63
measure: Evaluation of antiviral immunity
timeFrame: Day 85
measure: Evaluation of antiviral immunity
timeFrame: Day 85
measure: Evaluation of antiviral immunity
timeFrame: Day 85
Other outcomes:
Locations:
city: Portland
country: United States
facility: Portland Providence Medical Center
state: Oregon
Study officials:
affiliation: Providence Health & Services
name: Brendan D. Curti, MD
role: PRINCIPAL_INVESTIGATOR
References: