FDA Grants Fast Track Designation to ST101 for Recurrent Glioblastoma

Barry Kappel, PhD, MBA

The FDA has granted a fast track designation to ST101, a peptide antagonist of C/EBPβ, for the treatment of patients with recurrent glioblastoma, according to an announcement from Sapience Therapeutics, Inc., the drug developer.¹

The decision is supported by data from a phase 1/2 trial (NCT04478279) that is currently examining ST101 in patients with advanced unresectable and metastatic solid tumors; this includes an expansion cohort of patients with glioblastoma.²

Data showcased the clinical proof-of-concept of the agent. A confirmed partial response (PR) was reported in 1 patient with cutaneous melanoma per RECIST v1.1 criteria, and evidence of long-lasting stable disease was observed in several additional patients with refractory solid tumors.

"Glioblastoma is the most aggressive, fatal form of brain cancer with limited-to-no therapeutic options,” Barry Kappel, PhD, MBA, chief executive officer and president of Sapience Therapeutics, Inc., stated in a press release. “With the efficacy data from solid tumors and its ability to cross the blood–brain barrier, ST101 could meaningfully improve outcomes for patients battling this debilitating disease and we look forward to advancing it into phase 2.”

ST101 was developed to substantially reduce the expression of C/EBPβ target genes/proteins involved in cell survival, proliferation, and differentiation, including BCL-2, MCL-1, BIRC5/survivin, cyclins, and the ID family of proteins.3 The agent has been shown to have selective cancer cell cytotoxicity spanning several cancer types, including glioblastoma, breast cancer, melanoma, prostate cancer, lung cancer, and acute myeloid leukemia.

In the open-label, 2-part, dose-finding study, investigators have set out to identify the safety, tolerability, pharmacokinetics, pharmacodynamics, and proof-of-concept of ST101, given intravenously, to patients with advanced solid tumors. The trial is comprised of 2 phases, the dose-escalation and -expansion phases, and it is slated to enroll up to 162 patients.

To be eligible for enrollment, patients had to be 18 years of age or older and an ECOG performance status of 0 or 1. For the dose-escalation phase of the research, patients needed to have locally advanced or metastatic inoperable melanoma, carcinoma, or sarcoma. In the expansion phase of the research, they needed to have hormone receptor (HR)–positive locally advanced or metastatic breast cancer, castration-resistant prostate cancer (CRPC), melanoma, or glioblastoma. Those enrolled also needed to have evaluable disease per RECIST v1.1 criteria, and disease that had progressed on, or was not responsive to, the previous lines of therapy.

Those who had received a small molecule TKI within 2 weeks of initiating the study drug, or who had any other active malignancy were excluded. Additionally, those enrolled to the glioblastoma cohort could not have received any prior treatment for their disease that was not considered to be standard of care.

The primary end points of the trial were dose-limiting toxicities and adverse effects, and key secondary end points focused on area under the plasma concentration time curve of ST101, peak plasma concentration of the agent, elimination half-life of the agent, as well as overall response, disease control rate, duration of response, and progression-free survival.

Once the final dose-escalation cohort is completed, Sapience Therapeutics, Inc. shared plans to initiate 4 phase 2 expansion cohorts, which will include patients with refractory, locally advanced and metastatic cutaneous melanoma, HR-positive breast cancer, CRPC, and glioblastoma. This phase of the study is estimated to begin in the second half of 2021.

“This is an exciting regulatory milestone for our program,” Gina Capiaux, PhD, head of Regulatory Affairs at Sapience Therapeutics, Inc., added in the release. “Fast track designation for ST101 highlights this unmet need and allows us to work closely with the FDA to deliver this novel therapy to people with GBM as soon as possible.”

Previously, ST101 was granted an orphan drug designation from the FDA, as well as an orphan medicinal product designation from the European Commission, for the treatment of glioma.

References

1. Sapience Therapeutics receives FDA fast track designation for ST101 for the treatment of recurrent glioblastoma multiforme (GBM). News release. Sapience Therapeutics, Inc.; December 6, 2021. Accessed December 6, 2021. https://prn.to/3lGZTdj
2. A phase 1-2 study of ST101 in patients with advanced solid tumors. ClinicalTrials.gov. Updated November 10, 2021. Accessed December 6, 2021. https://clinicaltrials.gov/ct2/show/NCT04478279