On September 20, 2018 Galectin Therapeutics Inc. (NASDAQ:GALT), the leading developer of therapeutics that target galectin proteins, and Providence Cancer Institute, reported additional preliminary clinical data from cohort 3 of an investigator-initiated Phase 1b clinical trial of GR-MD-02 used in combination with KEYTRUDA (pembrolizumab) in patients with metastatic melanoma for which KEYTRUDA is indicated or those patients whose melanoma progressed during or recently after KEYTRUDA monotherapy (Press release, Galectin Therapeutics, SEP 20, 2018, View Source [SID1234530280]).

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The Providence Cancer Institute (Portland, OR) translational medicine team is conducting this phase 1b clinical trial, initiated under direction of principal investigator Brendan D. Curti, M.D., Director, Providence Melanoma Program. The objectives of this study were to determine a safe dose of GR-MD-02 used in combination with KEYTRUDA and to measure the response rate to combined therapy. "We are very encouraged by the objective response rate and the disease control rate observed in patients with advanced melanoma. These response rates were higher than expected with KEYTRUDA alone," said Dr. Curti. "An objective response rate of seven out of fourteen patients (50%) and a disease control rate of nine out of fourteen patients (64%) with advanced melanoma is very encouraging. The published objective response rates in randomized studies using KEYTRUDA in patients with advanced melanoma range from 21% in patients who have had prior therapy to 39% in patients who had not received prior systemic therapy. Importantly, the combination was also very well tolerated, and treatment appears to be associated with fewer adverse events than expected with KEYTRUDA alone."

When aggregated with the cohorts previously reported, the data shows a 50% objective response rate in advanced melanoma with GR-MD-02 in combination with KEYTRUDA and a significant decrease in the frequency of suppressive myeloid-derived suppressor cells (MDSC) following treatment in the responding patients (on day 85 post-treatment) was observed. The published data on KEYTRUDA alone have shown an objective response rate of 33% in this patient population.

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Fourteen advanced melanoma patients across three dose cohorts now have Objective Response Rate (ORR) and Disease Control Rate (DCR) data. Six patients in cohort 3 (8 mg/kg GR-MD-02) have now been added to the three patients in cohort 2 (4 mg/kg GR-MD-02) and the five patients in cohort 1 (2 mg/kg GR-MD-02). Cohorts 1 and 3 each had two patients with an objective response. All three patients in cohort 2 had an objective response.
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N=13; 1 patient in cohort 3 not depicted due to clinical progression prior to scans. Dotted line at -30% change from baseline indicates the RECIST 1.1 threshold for definition of partial response.

Generally, the U.S. Food and Drug Administration has defined objective response rate as the sum of partial responses plus complete responses. Disease control rate is the objective responses plus those with stable disease.

In addition to the fourteen advanced melanoma patients, six patients with head and neck cancer were enrolled in this phase 1b trial with a 33% objective response rate and a 67% disease control rate. Dr. Curti states "the response rates observed overall in advanced melanoma and head and neck cancer patients were better than expected with KEYTRUDA alone and are the basis for moving forward with both tumor types, particularly given the low response rates of anti-PD-1 monotherapy in head and neck cancer. There is a significant clinical need for better options for these patients and our initial objective response rates were encouraging enough to warrant inclusion of additional patients to help determine whether we should also pursue these challenging patient populations in a phase 2 trial. Taken together with the observed favorable safety and tolerability of the combination, these results provide a compelling rationale to move forward with this approach." Given that all three melanoma patients (100%) were responders at 4 mg/kg dose, the investigators plan to continue the trial with expansion of the 4 mg/kg GR-MD-02 and KEYTRUDA cohort to include additional advanced melanoma patients and additional head and neck cancer patients.

"In addition to the encouraging clinical responses seen thus far, we continue to make progress on identifying immunological biomarkers that correlate with favorable responses," said William L. Redmond, Ph.D., Associate Member, Laboratory of Cancer Immunotherapy, and Director, Immune Monitoring Laboratory at the Earle A. Chiles Research Institute, a division of Providence Cancer Institute. "We have observed a significant decrease in the frequency of suppressive myeloid-derived suppressor cells (MDSC) following treatment in the responding patients (on day 85 post-treatment). Comprehensive laboratory studies are being performed to further identify the biological mechanisms associated with this response."

"Galectin Therapeutics is very pleased with our continuing collaboration with Providence Cancer Institute, and we are encouraged that Dr. Curti and his team are expanding the trial to include additional patients," said Harold Shlevin, Ph.D., CEO and President of Galectin Therapeutics. "The planned expansion of the size of the 4 mg/kg dose cohort, and inclusion of both advanced melanoma patients and patients with head and neck cancer, will permit further evaluation that the use of GR-MD-02 in combination with KEYTRUDA has a better objective response rate and fewer adverse events than KEYTRUDA alone. We believe this collaboration with Providence to be a fruitful approach to helping to determine the potential of GR-MD-02 in combination immuno-therapy, and it also leverages our ability to collect additional data related to the immunological monitoring of these patients before potentially proceeding to the next phase of development."

Additional information about this clinical trial may be found at www.clinicaltrials.gov/ct2/show/NCT02575404

About GR-MD-02

GR-MD-02 is a complex carbohydrate drug that targets galectin-3, a critical protein in the pathogenesis of fatty liver disease and fibrosis. Galectin-3 plays a major role in diseases that involve scarring of organs including fibrotic disorders of the liver, lung, kidney, heart and vascular system. The drug binds to galectin-3 proteins and disrupts its function. Preclinical data in animals have shown that GR-MD-02 has robust treatment effects in reversing liver fibrosis and cirrhosis. GR-MD-02 also has robust efficacy in pre-clinical cancer models in combination with immunotherapy agents.