Interim clinical data from a phase 1/2 clinical trial of ST101 in refractory solid tumors leads to the expansion of the phase 2 glioblastoma arm of the study.
Expansion of the phase 2 glioblastoma study arm has been announced for the phase 1/2 clinical trial (NCT04478279) of ST101 in patients with advanced unresectable and metastatic solid tumors, according to a press release from Sapience Therapeutics, Inc.1
Interim clinical data is the basis of the expansion, as a patient with glioblastoma enrolled in the trial demonstrated a confirmed partial response (PR) per mRANO (>50% reduction in tumor measurements) when given the first-in-class antagonist of C/EBPβ, ST101.
Currently, 14 patients have been enrolled in the phase 2 expansion portion of the ongoing study. Among the 14 patients are 1 who has achieved a confirmed PR after treatment with ST101 for 18 weeks, 7 who have not yet reached the first on-study assessment, and 6 patients who have experienced progression.
"ST101 is showing promising results in glioblastoma with a PR, which we have confirmed with repeat scans per mRANO and using an independent radiology reviewer. The tumor shrinkage we are seeing is especially encouraging given the significant unmet medical need in this disease and its poor prognosis," Fabio Iwamoto, principal investigator at Columbia University, stated in the press release. "Our team at Columbia is thrilled to be a part of this work and to deliver meaningful therapeutic benefits to [patients with] cancer."
Within the phase 1 portion of the study, 25 patients with multimetastatic disease who were refractory to standard therapy were enrolled.2 Patients had refractory solid tumors with varying histologies and were enrolled to determine the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and proof-of-concept efficacy of ST101.
A 3+3 dose-escalation design was used in the study with ST101 being given intravenously at a dose of 0.5, 1, 2, 4, 6, 9 mg/kg or a flat dose of 500 mg. The primary end point of the study was to evaluate safety and tolerability of ST101 as well as to determine the recommended phase 2 dose. Secondary and exploratory end points included PK, preliminary efficacy per RECIST 1.1, and PD evaluation.
Data from the phase 1 portion of the ongoing ST101 study were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, and by February 15, 2022, 5 patients remained on the study with a median treatment duration of 27 weeks (range, 16-77).2
Findings revealed that no dose-limiting toxicities, dose modifications, or serious adverse events (AEs) related to ST101 were seen in the study patients. Of note, the most common and only consistent AE was G1-2 histaminergic infusion-related reactions (IRRs), consisting of mostly pruritus and urticaria. This was managed with antihistamines, montelukast, and interruption/slowing of infusion.
A total of 93% of patients on the first dose at 4 mg/kg or more were affected with IRRs which led to a prolonged time of infusion. Both the intensity and the frequency of IRRs decreased with repeat dosing. Further, no other AEs were consistently reported, and no evidence of accumulation upon continued exposure of ST101 or anti-drug antibodies were seen in patients.
Additionally, several patients with decreased Ki67 expression had tumor immunohistochemistry which showed dose-proportionate staining for ST101 as well as a decreased tumor proliferation. Flat dosing was supported in the population PK analysis in phase 2.
Overall, the results of the phase 1 portion of the study have demonstrated ST101 to have a favorable safety profile. Based on these findings and the confirmed PR found in the glioblastoma patients, the phase 2 portion of the study intends to expand the recurrent glioblastoma cohort and enroll additional patients.
"The confirmed response in glioblastoma is very exciting news, which along with the continuing clinical benefit we are seeing from some of the phase 1 patients, suggests that ST101 could make a major contribution to the treatment of cancer. Based on its novel mechanism of action, ST101 is the first in a new class of peptide therapeutics, and we look forward to advancing our phase 2 study," Alice Bexon, MD, chief medical officer of Sapience, said in the press release.