NCT06896188

9-ING-41 Combined With Retifanlimab, Plus Modified FOLFIRINOX for Patients With Advanced Pancreatic Adenocarcinoma (RiLEY)

A Phase Ib Study of 9-ING-41 (Elraglusib), a Glycogen Synthase Kinase 3-beta (GSK-3β) Inhibitor, Combined With Retifanlimab, a PD-1 Inhibitor, Plus Modified FOLFIRINOX as Frontline Therapy for Patients With Advanced Pancreatic Adenocarcinoma (RiLEY)

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: Anwaar Saeed · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a study of the combination of 9 ING-41 (elraglusib) and retifanlimab plus mFOLFIRINOX in patients with pancreatic cancer without prior systemic therapy for advanced disease. The safety lead-in cohort will consist of 6 patients, followed by dose de-escalation if necessary, based on safety assessments. After evaluating the safety and tolerability at the initial dose level, the study will proceed to an expansion cohort at the determined safe dose level, with the total maximum enrollment not exceeding 12 patients for the entire study.

Detailed description

Given the role of GSK-3β in immune regulation, the combination of GSK-3β inhibition with PD 1 inhibition may be expected to provide synergistic anti-tumor efficacy. The excellent safety profile of 9-ING-41, along with preclinical and clinical evidence of anti-tumor activity in pancreatic cancer, provides a strong rationale to evaluate the efficacy of 9-ING-41 in combination with a PD 1 inhibitor plus standard chemotherapy (mFOLFIRINOX) as frontline therapy for patients with advanced PDAC. The PD-1 inhibitor to be used in the present study is retifanlimab, a humanized, hinge-stabilized immunoglobulin G4 (IgG4) monoclonal antibody. Retifanlimab has shown positive results for the treatment of patients with squamous carcinoma of the anal canal (SCAC) who have progressed after first-line chemotherapy treatment. In the Phase 2 PODIUM-202 trial, retifanlimab was well-tolerated at a dose of 500 mg administered via IV infusion every 4 weeks (28-day cycle) for up to 2 years.The combination of 9-ING-41 and retifanlimab with mFOLFIRINOX has not previously been administered to human subjects. In the 1801 study, 9-ING-41 has been administered in combination with various chemotherapy regimens including irinotecan,and has been well-tolerated. Retifanlimab alone has been well-tolerated when administered for up to 2 years in patients with anal cancer. Overall, based on previous nonclinical and clinical experience, both of these agents appear to have an acceptable safety profile and do not appear to have significant overlapping toxicities. However, it is possible that when they are administered together and in combination with mFOLFIRINOX, more frequent or severe AEs, or new AEs not previously observed with any of these agents administered alone, may occur. It is not known if administration of 9-ING-41 and retifanlimab will act synergistically to provide increased anti-tumor activity compared to mFOLFIRINOX alone. Subjects in this study should not expect to benefit directly by their participation in the study. The data collected in this study may benefit future cancer patients

Conditions

• Pancreatic Adenocarcinoma

Interventions

Type	Name	Description
DRUG	Retifanlimab	(PD-1)-blocking monoclonal antibody
DRUG	Chemotherapy	oxaliplatin - Antineoplastic - Platinum Complexes Chemotherapy agent; leucovorin - a form of Folic acid helps the body produce and maintain new cells, and also helps prevent changes to DNA that may lead to cancer; irinotecan - anti-cancer medication used to treat colon cancer in combination with other chemotherapeutic agents; 5-FU - 5-fluorouracil is used to treat cancer in combination with other chemotherapeutic agents
DRUG	9-ING-41	a maleimide-based ATP-competitive and selective glycogen synthase kinase-3β (GSK-3β) inhibitor with an IC50 of 0.71 μM. 9-ING-41 significantly leads to cell cycle arrest, autophagy and apoptosis in cancer cells

Timeline

• Start date: 2025-09-22
• Primary completion: 2027-09-30
• Completion: 2028-12-31
• First posted: 2025-03-26
• Last updated: 2025-09-29

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study