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A Phase 1 Safety Study of Evexomostat (SDX-7320) in Patients with Late-Stage Cancer: An Antiangiogenic,
Monica M Mita1, Alain C Mita1, Bradley J Carver2
1Hoag, Newport Beach, California.
Purpose:
To investigate the safety and tolerability of evexomostat (SDX-7320) in patients with late-stage cancer.
Patients And Methods:
This phase 1 dose-escalation safety study used an accelerated titration followed by a 3 + 3 design on 7- or 14-day administration, with dose expansion at the recommended phase 2 dose in 32 patients with late-stage, solid tumors. Measurements included standard assessments of safety, tolerability, target engagement in whole blood, plasma levels of protein biomarkers, and drug exposure. Tumor response was measured using RECIST v.1.1.
Results:
Thirty-two patients were dosed with evexomostat (SDX-7320), starting at 1.7 mg/m2 once per week and escalated to 65 mg/m2 (once every 2 weeks, 28 days/cycle). Dose escalation and expansion confirmed the maximum tolerated dose at 49 mg/m2 once every 2 weeks with reversible thrombocytopenia as the dose-limiting toxicity. Most treatment-emergent adverse events were of grade 1 or 2 in severity and nonserious, with no grade 5 adverse events. Eighty percent of patients (n = 20/25 evaluable) had stable disease, and the average treatment duration was 87 days (3.1 cycles). Key angiogenic biomarkers VEGF-C and bFGF (FGF2) improved in response to evexomostat. Patients with baseline insulin resistance (i.e., fasting insulin >20 µU/mL; n = 11) exhibited significant decreased fasting insulin after treatment. Decreases in leptin were observed in 27/31 patients (87%), whereas adiponectin increased in 28/31 patients (90%). Plasma lipid profiles showed increased high-density lipoprotein (HDL) and decreased low-density lipoprotein (LDL) cholesterol.
Conclusions:
Evexomostat (SDX-7320) was well-tolerated with prolonged stable disease and metastatic control in an open-label, phase I safety study. Improvements were observed in angiogenic and metabolic biomarkers.
Significance:
Obesity and insulin resistance are known to promote tumor growth and accelerate the mortality of patients with cancer. Evexomostat is a novel antiangiogenic and antimetastatic drug candidate which also has insulin-sensitizing and antiobesity properties that is being developed for use in combination with standard-of-care therapies for obese patients with cancer.
Insights
Evexomostat (SDX-7320) showed good tolerability in a Phase 1 study for advanced cancer patients. The drug demonstrated prolonged stable disease and improved metabolic and angiogenic biomarkers.
Area of Science:
- Oncology
- Pharmacology
- Metabolic Syndrome
Background:
- Obesity and insulin resistance are linked to increased cancer progression and mortality.
- Evexomostat (SDX-7320) is a novel drug candidate with antiangiogenic, antimetastatic, insulin-sensitizing, and antiobesity properties.
- The drug is being developed for combination therapy in obese cancer patients.
Purpose of the Study:
- To evaluate the safety and tolerability of evexomostat (SDX-7320) in patients with advanced-stage cancer.
- To determine the maximum tolerated dose (MTD) and dose-limiting toxicities.
- To assess preliminary efficacy, including tumor response and biomarker modulation.
Main Methods:
- Phase 1, open-label, dose-escalation safety study with dose expansion.
- Utilized an accelerated titration followed by a 3+3 design.
- 32 patients with late-stage solid tumors received evexomostat with varying schedules and doses.
Main Results:
- The MTD was determined to be 49 mg/m2 every 2 weeks, with reversible thrombocytopenia as the dose-limiting toxicity.
- 80% of evaluable patients achieved stable disease, with an average treatment duration of 87 days.
- Significant improvements were observed in angiogenic biomarkers (VEGF-C, bFGF) and metabolic markers (insulin, leptin, adiponectin, HDL, LDL).
Conclusions:
- Evexomostat (SDX-7320) is well-tolerated in patients with advanced cancer.
- The drug demonstrated potential for prolonged stable disease and metastatic control.
- Observed improvements in angiogenic and metabolic biomarkers suggest a multifaceted therapeutic benefit.
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