BXQ-350, a nanovesicle formulation of saposin C, has shown promising tolerability and clinical activity in patients with advanced solid tumors or high-grade glioma, according to data from a first-in-human phase 1 trial (NCT02859857) published in Clinical Cancer Research. The study suggests that BXQ-350, a first-in-class biologic, may offer a new therapeutic avenue for patients with limited treatment options.
Safety and Tolerability
The dose-escalation portion of the phase 1 study (n = 18) revealed no dose-limiting toxicities, and the maximum tolerated dose (MTD) was not reached. Across the entire study population (n = 86), including 68 patients who received the agent at 2.4 mg/kg, adverse events (AEs) led to treatment discontinuation in 10% of patients. The most common treatment-related AEs were nausea (24%) and fatigue (23%).
Efficacy Signals
Notably, 8 patients achieved a progression-free survival (PFS) of at least 6 months. Among these, 2 patients experienced a partial response, and 6 had stable disease. Impressively, 7 patients remained on the study for over 12 months, 5 for over 24 months, and 2 patients remained on study without disease progression for 7 years.
Robert Wesolowski, MD, a clinical professor of internal medicine at the Ohio State University Comprehensive Cancer Center—James in Columbus, commented, "These data provide a large body of work on the use of BXQ-350 in patients. In a population with such advanced disease, the fact that 2 patients are alive without disease progression 7 years after initiating BXQ-350 treatment is remarkable."
Study Design and Patient Population
The open-label, dose-escalation study enrolled patients aged 18 to 80 with histologically or cytologically confirmed advanced solid tumors who had exhausted standard therapy options or had contraindications to such therapies. Patients with high-grade glioma were required to have unequivocal evidence of recurrence or disease progression per MRI, or histologically proven tumor recurrence, and prior treatment with radiotherapy and temozolomide. Key inclusion criteria included measurable or non-measurable disease per RECIST 1.1 or RANO criteria, an ECOG performance status of 0 to 2, and acceptable organ function.
During dose escalation, BXQ-350 was administered at doses ranging from 0.7 mg/kg to 2.4 mg/kg. Subsequent evaluation involved administering the agent at 2.4 mg/kg to patients with ependymoma, gastrointestinal tumors, or advanced solid tumors other than high-grade glioma.
The primary endpoint in the dose-escalation phase was determining the MTD. In subsequent phases, primary endpoints included preliminary antitumor efficacy per RECIST 1.1 or RANO criteria and antitumor efficacy per RECIST 1.1 criteria. Secondary endpoints included pharmacokinetics, PFS, time to response, and duration of response.
Future Directions
"We are excited to have our phase 1 monotherapy data published in Clinical Cancer Research," stated Jim Beach, chief executive officer and president of Bexion Pharmaceuticals. "These data demonstrate the safety and tolerability of BXQ-350 in a large population with advanced solid tumor disease and high-grade glioma. We are now generating data on the use of BXQ-350 in metastatic colorectal cancer [mCRC]."
Bexion Pharmaceuticals is currently evaluating BXQ-350 in combination with standard-of-care therapy (mFOLFOX7 and bevacizumab) in patients with newly diagnosed mCRC in the ongoing phase 1b/2 ASIST trial (NCT05322590).
