NCT06736717

Onvansertib in Combination With NALIRIFOX for First Line Treatment of Advanced Pancreatic Cancer

A Phase 1b/2 Trial of Onvansertib in Combination With NALIRIFOX for First Line Treatment of Advanced Pancreatic Cancer

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 21 (estimated)
• Sponsor: University of Kansas Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Pancreatic cancer is a deadly disease and will be the second leading cause of cancer related death behind lung cancer by 2030. Over 62,000 people are diagnosed each year in the United States with about 90% succumbing to the disease within 5 years. In the metastatic setting, NALIRIFOX, FOLFIRINOX and nab-paclitaxel-gemcitabine are standard treatment options in patients with good performance status (Eastern Cooperative Oncology Group \[ECOG\] 0/1). All three combinations have shown a survival advantage over previously standard gemcitabine-based therapy, with 11.1 months overall survival (OS) for NALIRIFOX/FOLFIRINOX and 8.7 months for nab-paclitaxel-gemcitabine versus 6.7 months for gemcitabine alone. There is an urgent need to improve treatment of patients with current and emerging therapeutic strategies. KRAS is the most common oncogene mutated in pancreatic adenocarcinoma, and it is mutated in nearly all tumors. Mutant KRAS is essential for PDAC growth, where the constitutive activated RAS proteins contribute to tumorigenesis, treatment resistance, and metastases. Despite research and drug development efforts focused on KRAS, no effective RAS inhibitors have been approved for the treatment of pancreatic cancer with KRAS mutation. The poor prognosis of KRAS-mutated PDAC patients and the absence of KRAS-targeted therapies, highlight the urgency to develop novel therapies aimed at KRAS. This study will investigate onvansertib (also known as PCM-075 and NMS-1286937) as the first PLK1-specific adenosine triphosphate competitive inhibitor administered by oral route to enter clinical trials with proven antitumor activity in different preclinical models.

Conditions

• Pancreatic Cancer

Interventions

Type	Name	Description
DRUG	Onvansertib	20 or30mg flat dose - depending on results from safety lead-in. Administered concurrently with NALIRIFOX. Once daily on D1-5 of each 14-day cycle.
DRUG	NALIRIFOX	Chemotherapy regimen of nanoliposomal irinotecan, oxaliplatin, fluorouracil \[5-FU\], and leucovorin. Intravenously on Day 1 of each 14-day cycle.

Timeline

• Start date: 2025-02-01
• Primary completion: 2026-07-01
• Completion: 2027-01-01
• First posted: 2024-12-17
• Last updated: 2025-02-06

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study