Early Data for OMX-0407 Fuel Expansion Cohorts in RCC, Angiosarcoma

Treatment with the first-in-class SIK inhibitor OMX-0407 was safe and demonstrated evidence of anticancer activity in heavily pretreated patients with advanced solid tumors, according to data from the dose-escalation portion of a phase 1a/b trial (NCT05826600).¹

Topline data from the dose-escalation portion of the study showed that 1 patient with a solid tumor that was resistant to multiple prior lines of chemotherapy experienced a durable complete response (CR). Based on these data, expansion cohorts will be opened to further investigate OMX-047 for the treatment of patients with renal cell carcinoma (RCC) and angiosarcoma.

“We are now focusing on generating efficacy data in the dose-expansion segment of the study. The first two indications, kidney cancer and angiosarcoma, amongst other prioritized key solid tumor indications, have a high potential for objective response to OMX-0407 based on the results of the dose escalation and the preclinical data package,” Hannes Loferer, PhD, chief operations officer of iOmx Therapeutics, stated in a news release.

OMX-0407 is designed to directly disrupt tumor cell proliferation via the modulation of tyrosine kinase signaling. The agent is intended to enhance tumor cell apoptosis in response to death receptor ligands such as tumor necrosis factor, thereby causing changes in the tumor microenvironment.

The open-label study is enrolling patients at least 18 years of age with cytologically or pathologically confirmed advanced cancer who completed or were unsuitable for licensed therapies for their primary tumor, unless those treatments were not available.² All patients are required to have an ECOG performance status of 0 to 2, an evaluable tumor per RECIST 1.1 criteria, and resolution of all toxicities from prior anticancer therapy to grade 1 or stable grade 2.

Patients with RCC need to have histologically confirmed clear cell histology with at least 70% of the reviewed tumor presenting as clear cell. Prior treatment with PD-1 and VEGF inhibition is required. Those with renal vascular involvement should be receiving stable anticoagulation at the start of study treatment. Those with squamous non–small cell lung cancer (NSCLC) must have histologically confirmed disease and prior treatment with a PD-1 inhibitor and platinum chemotherapy; prior targeted therapy is also required for patients with NSCLC harboring EGFR mutations or ALK rearrangements. Patients with urothelial carcinoma must have histologically confirmed disease and prior treatment with a PD-1 inhibitor and a NECTIN-4–targeted agent.

Key exclusion criteria for all patients include untreated central nervous system metastases; an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level higher than 2.5 times the upper limit of normal (ULN), except for those with hepatic metastases where AST or ALT levels are not allowed to be more than 5 times the ULN; an activated partial thromboplastin time higher than 1.5 times the ULN; persistent fever or other signs of uncontrolled infection; and personal or family history of long QT syndrome or sudden death. Patients with RCC cannot have uncontrolled hypertension, and those with RCC, NSCLC, or urothelial carcinoma cannot have received more than 3 prior lines of therapy in the metastatic setting.

The starting dose of OMX-0407 was 20 mg split into 10 mg twice per day.2 Dose escalation featured a 3+3 design intended to evaluate the agent’s safety and determine the maximum tolerated dose. Dose expansion will evaluate the agent in cohorts featuring up to 86 patients with previously treated RCC or angiosarcoma.¹

Dose-limiting toxicities and objective response rate are serving as the trial’s primary end points. Secondary end points consist of determining the MTD; safety and tolerability; pharmacokinetics; duration of response; and progression-free survival.²

“Kicking-off the phase 1b segment of the OMX-0407 trial is a key development milestone for iOmx. The dose-escalation data, including 1 long-lasting CR in an indication of high medical need and additional signs of anti-tumor activity in other patients is very strong,” Apollon Papadimitriou, PhD, chief executive officer of iOmx Therapeutics, stated in a news release.1 “We are confident that we are progressing towards providing a clinically meaningful, differentiated therapy for patients failing current cancer treatments and expect to report topline clinical proof-of-concept data by early 2026.”

References

1. iOmx Therapeutics initiates phase Ib with OMX-0407. News release. iOmx Therapeutics. August 22, 2024. Accessed August 26, 2024. https://iomx.com/wp-content/uploads/2024/08/20240822_iOmx_PR_Ph1b-Expansion-Start_FINAL_ENG.pdf
2. A study of OMX-0407 in patients with previously treated solid tumours that can't be removed surgically. ClinicalTrials.gov. Updated May 16, 2024. Accessed August 26, 2024. https://clinicaltrials.gov/study/NCT05826600