BXQ-350 Is Well Tolerated, Shows Clinical Activity in Advanced Solid Tumors

Robert Wesolowski, MD

Treatment with the BXQ-350, a nanovesicle formulation of saposin C, was well tolerated and generated signals of efficacy 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.^1,2

Findings showed that patients treated during the dose-escalation portion of the study (n = 18) did not experience any dose-limiting toxicities, and the maximum tolerated dose (MTD) was not reached. Including an additional 68 patients who received the agent at 2.4 mg/kg, adverse effects (AEs) led to treatment discontinuation in 10% of patients. The most common treatment-related AEs included nausea (24%) and fatigue (23%).²

Regarding efficacy, 8 patients achieved a progression-free survival (PFS) of at least 6 months. Two of these patients experienced a partial response, and 6 of these patients had stable disease. In this group of patients, 7 stayed on study for more than 12 months, 5 remained on study for more than 24 months, and 2 patients remained on study without disease progression for 7 years.

“These data provide a large body of work on the use of BXQ-350 in patients,” Robert Wesolowski, MD, a clinical professor of internal medicine at the Ohio State University Comprehensive Cancer Center—James in Columbus, stated in a news release.¹ “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.”

BXQ-350 is a first-in-class biologic that contains the multifunctional, sphingolipid activator protein Saposin C along with a phospholipid.

The first-in-human, open-label, dose-escalation study enrolled patients 18 to 80 years of age with histologically or cytologically confirmed advanced solid tumors who did not have further standard therapy available or had a contraindication for standard therapy.³ Patients with high-grade glioma were required to have unequivocal evidence of recurrence or disease progression per MRI, or histologically proven tumor recurrence. Those with high-grade glioma were also required to have received prior treatment with radiotherapy and temozolomide (Temodar).

Other key inclusion criteria for all patients included measurable or non-measurable disease per RECIST 1.1 criteria or RANO criteria; an ECOG performance status of 0 to 2; and acceptable liver, renal, and bone marrow function.

During dose escalation, patients received BXQ-350 at doses ranging from 0.7 mg/kg to 2.4 mg/kg.² In part 2, the agent was further evaluated at the highest planned dose from the dose-escalation portion of the study, and in part 3, patients with ependymoma, gastrointestinal tumors, or advanced solid tumors other than high-grade glioma were given BXQ-350 at 2.4 mg/kg.³

Determining the MTD was the primary end point in part 1 of the study. In part 2, the primary end point was preliminary antitumor efficacy per RECIST 1.1 or RANO criteria. Antitumor efficacy per RECIST 1.1 criteria was the primary end point in part 3. Secondary end points in part 2 included pharmacokinetics, PFS, time to response, and duration of response.

“We are excited to have our phase 1 monotherapy data published in Clinical Cancer Research,” Jim Beach, chief executive officer and president of Bexion Pharmaceuticals, stated in a news release.¹ “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].”

The ongoing phase 1b/2 ASIST trial (NCT05322590) is evaluating BXQ-350 in combination with standard-of-care therapy consisting of mFOLFOX7 (leucovorin calcium, fluorouracil, and oxaliplatin) and bevacizumab (Avastin) in patients with newly diagnosed mCRC.^1,4

References

1. Bexion Pharmaceuticals, Inc. announces publication of phase 1 data for BXQ-350 in advanced solid tumors. News release. Bexion Pharmaceuticals. October 31, 2024. Accessed November 4, 2024. https://www.prnewswire.com/news-releases/bexion-pharmaceuticals-inc-announces-publication-of-phase-1-data-for-bxq-350-in-advanced-solid-tumors-302293463.html
2. Rixe O, Villano JL, Wesolowski R, et al. A first-in-human phase 1 study of BXQ-350, a first-in-class sphingolipid metabolism regulator, in patients with advanced/recurrent solid tumors or high-grade gliomas. Clin Cancer Res. Published online September 12, 2024. doi:10.1158/1078-0432.CCR-24-1721
3. Phase 1 study of BXQ-350 in adult patients with advanced solid tumors. ClinicalTrials.gov. Updated July 22, 2021. Accessed November 4, 2024. https://clinicaltrials.gov/study/NCT02859857
4. BXQ-350 in newly diagnosed metastatic colorectal carcinoma (ASIST). ClinicalTrials.gov. Updated August 28, 2024. Accessed November 4, 2024. https://clinicaltrials.gov/study/NCT05322590