FDA Orphan Drug Designation Granted to ST101 for Advanced Cutaneous Melanomas

The FDA granted a fast track designation to ST101 for the treatment of advanced cutaneous melanoma in patients who have disease progression on or after anti-PD-1/anti-PD-L1 therapy, according to a press release by Sapience Therapeutics, Inc.

ST101 is a peptide antagonist of C/EBPB. The agent has demonstrated clinical proof of concept with a confirmed partial response in a patient with cutaneous melanoma and evidence of long-lasting stable disease in several additional patients. It was previously granted an orphan drug designation.

"This is the second Fast Track designation received for ST101, underscoring the advancement of our ST101 program and its potential therapeutic benefit for both melanoma and glioblastoma multiforme patients. We are grateful for the opportunity to quickly advance the development of ST101 for patients in need,” said Gina Capiaux, PhD, sapience's Head of Regulatory Affairs, in a press release.

The agent is currently being evaluated in a phase 1/2, open-label, non-randomized, study (NCT04478279) with an estimated enrollment of 162 participants and an estimated completion date of January 2024. The primary end points of the study are the rate of dose-limiting toxicities and the rate of adverse events up to 20 months. Secondary end points include area under the curve, Cmax, terminal half-life, overall response, disease control rate, duration of response, and progression-free survival.

During the study, which included patients with solid tumors, ST101 will be administered intravenously once per week. The dose-escalation portion of the study follows a 3 + 3 design. The dose cohorts are 0.5, 1, 2, 4, 8, and 16 mg/kg once weekly with the exception of 16 mg/kg, which will be dosed every other week.

The expansion phase will be made up of 4 specific tumor-types. Fifteen patients will be enrolled in each cohort and treated with the agent, if one or more responses is observed in the cohort, it will be expanded to 30 patients for further efficacy assessment. Cohort 1 will be made up of patients with hormone receptor+ locally advanced/metastatic breast cancer that has progressed after prior 1 to 2 hormone-based therapies. Cohort 2 will include patients with melanoma that has progressed after or on treatment with an immune checkpoint inhibitor that have received 1-2 prior lines of therapy of advanced/metastatic disease. Cohort 3 will include patients with glioblastoma that has recurred on progressed after 1 standard treatment regimen. Cohort 4 will be made up of patients with castration-resistant metastatic prostate cancer that progressed after previous treatment with taxanes.

"Melanoma is the fifth most diagnosed cancer in the United States, with more than 100,000 new cases per year, and no well-established standard of care treatment regimen. We believe we have a significant opportunity to deliver a novel therapeutic option with ST101, which has a durable clinical efficacy and an excellent safety profile, for melanoma patients whose disease has progressed following treatment with anti-PD-1 therapy,” said Barry Kappel, PhD, Sapience's CEO and president, in a press release.

In order to participate in the study, patients must be 18 years of age or older, have an ECOG performance status of 0 or 1, have a locally advanced or metastatic inoperable tumor, evaluable disease, and disease that progressed on, or is not response to previous lines of therapy. Patients with known hypersensitivity to ST1010, known active central nervous system metastases, any other active malignancy requiring systemic therapy, active HIV infection, active autoimmune disease, active immune thrombocytopenic purpura, or active infection requiring systemic therapy are not eligible to participate.

The study is currently recruiting in, or planning on recruiting in, California, Colorado, Illinois, Michigan, New York, North Carolina, and Tennessee.

_REFERENCES:

_{Sapience Therapeutics receives FDA fast track designation for ST101 for advanced cutaneous melanoma. News release. Sapience Therapeutics. December 15, 2021. Accessed December 15, 2021. https://bit.ly/3EYlW6U}

_{A phase 1-2 study of ST101 in patients with advanced solid tumors. ClinicalTrials.gov. Accessed December 15, 2021. https://bit.ly/3IUN9JY}