A Phase 1b/2a study to evaluate the efficacy and safety of BXQ-350 in combination with mFOLFOX7 and bevacizumab in newly diagnosed metastatic colorectal carcinoma patients (mCRC): Interim efficacy subset analyses

Background: Dysregulated sphingolipid metabolism is common to many cancer types, including mCRC, and leads to elevated concentrations of gangliosides (GM3), lactosylceramides (LacCer), glucosylceramides (GluCer) and sphingosine-1-phosphate (S1P) and lower concentration of ceramides (Cer). In mCRC patients, several studies have shown elevated concentrations of these sphingolipids are associated with worse prognosis and poor survival. Therefore, targeting dysregulated sphingolipid metabolism and returning sphingolipid metabolism to homeostasis could be a promising therapeutic approach. BXQ-350 is a nanovesicle of Saposin C, an allosteric activator of sphingolipid metabolism, that affects dysregulated sphingolipid metabolism. BXQ-350 lowers GM3, GluCer and S1P levels while it also increases ceramide levels promoting a return to homeostasis. Also, it is well documented that, in mCRC patients, sidedness, oncogenic mutations and sex have a significant impact on prognosis. Multiple reports suggest that right-sided patients have a worse prognosis than left-sided patients and post-menopausal females have, overall, a worse prognosis than male patients of a similar age. Method: BXQ-350 is being investigated in a Phase 1b/2a study in combination with mFOLFOX7 and Bevacizumab (SoC) in newly diagnosed mCRC patients (NCT05322590) to assess the efficacy and safety of BXQ-350. The Phase 1b/2a is a safety dose escalation part to establish the RP2D exploring 1.8 and 2.4 mg/kg BXQ-350 in combination with SoC. Primary objectives are to assess safety and preliminary efficacy of BXQ-350 in this combination. Secondary objectives include longitudinal analysis of several biomarkers, including sphingolipid profiling. Results: A total of 32 evaluable patients were enrolled, and all 32 patients have completed SoC treatment schedule plus BXQ-350. Amongst these 32 patients, 21(66%) are alive and in active follow-up. Of the 32 patients, 19 are female (59%) of which 15 are 55 years or older (79%); 15 are right-sided colon cancer (47%) and 17 are left-sided and rectal cancer patients. The disease control rate was 91% (30 pts had SD, PR or CR). As of September 2025, overall ORR and mPFS are 61% and 10.6 months; ORR for male and female patients are respectively 64.3% and 52.6% while mPFS 9.1 and 10.6 months respectively. ORR and mPFS for right-sided and left-sided patients are 60% and 52.9% respectively and mPFS 10.6 and 10.8 months. These results suggest a better than expected clinical outcome in female and right-sided subpopulations. Conclusions: BXQ-350 was safe and well tolerated in the combination. Interim analyses and ongoing monitoring of patients suggests that BXQ-350 may provide additional clinical benefits, especially in right-sided or female patients as illustrated by surprisingly better than expected ORR or mPFS in these patient populations compared to left-sided or male patients