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)
Anwaar Saeed
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.
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 immunogl…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Is able to understand and voluntarily sign a written informed consent and is willing and able to comply with the protocol requirements including scheduled visits, treatment plan, laboratory tests and other study procedures. * Is aged ≥ 18 years. * Has pathologically confirmed advanced, recurrent, or metastatic pancreatic cancer AND is previously untreated with systemic agents in the advanced/metastatic setting. * Must have at least 1 measurable lesion per RECIST v1.1. Lesions that are radiated should not count as target lesions unless there is evidence of growth post rad…
Interventions
- DrugRetifanlimab
(PD-1)-blocking monoclonal antibody
- DrugChemotherapy
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
- Drug9-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
Location
- UPMC Hillman Cancer CenterPittsburgh, Pennsylvania