ImmunoMet Therapeutics announced updated clinical data from its Phase 1b trial of Lixumistat in combination with gemcitabine and nab-paclitaxel as a frontline therapy for advanced pancreatic cancer (PDAC). The study, led by Dr. Shubham Pant at The University of Texas MD Anderson Cancer Center, suggests that Lixumistat, a metabolic inhibitor, may offer a novel approach to overcoming resistance and improving outcomes in this challenging disease.
The single-arm Phase 1b trial (NCT05497778) included a dose escalation phase followed by an expansion phase. Fourteen patients were treated, with eight receiving Lixumistat at 400 mg QD and six at 800 mg QD. The recommended Phase 2 dose (RP2D) of Lixumistat was determined to be 400 mg once daily when combined with gemcitabine and nab-paclitaxel.
Clinical Efficacy
Among the eight response-evaluable patients treated at the RP2D, the results showed promising clinical activity:
- Objective Partial Response (PR): 5 patients (62.5%)
- Stable Disease (SD): 3 patients (37.5%)
- Disease Control Rate (DCR): 100%
The estimated median Progression-free Survival (PFS) was 9.7 months (5.75-NA), and the median Overall Survival (OS) was 18 months (8.5-NA). The patient group had a mean age of 66.5 + 8 years, and 63% were female.
Expert Commentary
Dr. Pant commented on the findings: "Our study of Lixumistat at its RP2D in combination with gemcitabine/nab-paclitaxel shows quite encouraging clinical effects in this small signal-finding study. These findings suggest that the Lixumistat combination may provide a viable novel therapeutic option for advanced PDAC, warranting further investigation in larger studies."
Addressing Unmet Needs in Pancreatic Cancer
Pancreatic ductal adenocarcinoma (PDAC) remains a highly aggressive cancer with significant unmet needs. Dean Welsch, CEO of ImmunoMet Therapeutics, highlighted the importance of targeting cancer cell metabolism, particularly oxidative phosphorylation (OxPhos), in overcoming resistance to current therapies. "Based on these early clinical data, we are hopeful that this best-in-class OxPhos inhibitor can improve outcomes for these patients," Welsch stated.
Lixumistat: A Novel Metabolic Inhibitor
Lixumistat is a Protein Complex 1 (PC1) inhibitor that targets the oxidative phosphorylation (OXPHOS) pathway, crucial for tumor growth and proliferation in certain cancers. ImmunoMet is also exploring additional indications for Lixumistat, guided by a precision medicine approach.
Orphan Drug Designation
ImmunoMet has received Orphan Drug Designation for Lixumistat in patients with pancreatic cancer and glioblastoma multiforme (GBM), further supporting its potential in treating these rare and aggressive malignancies.
