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

NCT06896188 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HCC 24-106
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pancreatic Adenocarcinoma

Keywords

Glycogen Synthase Kinase 3-beta (GSK-3β) inhibitor; PD-1 inhibitor

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicities (DLTs)

  Dose Limiting Toxicities DLTs Adverse Events The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Treatment related Dose Limiting Toxicities (DLTs) will be monitored through the first 2 cycles of the study therapy (28 days). Follow up safety assessments will continue beyond the first 28 days and throughout the treatment on the trial to monitor for late onset treatment related adverse effects or toxicities

  Up to 28 days after start of treatment

Secondary Outcomes (8)

• Disease control rate (DCR) - imRECIST

  Up to 24 months

• Disease control rate (DCR) - RECIST v1.1

  Up to 24 months

• Objective response rate (ORR)

  Up to 24 months

• Duration of response (DOR)

  Up to 24 months

• Progression free survival (PFS)

  Up to 42 months

Study Arms (1)

Retifanlimab + 9-ING-41 + Chemotherapy

EXPERIMENTAL

1. Chemotherapy: oxaliplatin 85 mg/m2 IV, leucovorin 400 mg/m2 IV, irinotecan 150 mg/m2 IV, and 5-FU continuous IV infusion 2400 mg/m2 over 46 hours every 14 days 2. Retifanlimab: IV at 500 mg on day 1 of every other cycle (Cycles 1, 3, 5, etc) 3.9-ING-41: IV at 9.3 mg/kg twice weekly (days 1, 3, 8 and 11) for the first 4 cycles, then weekly (days 1 and 8) thereafter

Drug: Retifanlimab; Drug: Chemotherapy; Drug: 9-ING-41

Interventions

Retifanlimab DRUG

(PD-1)-blocking monoclonal antibody

Also known as: ZYNYZ

Retifanlimab + 9-ING-41 + Chemotherapy

Chemotherapy DRUG

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

Retifanlimab + 9-ING-41 + Chemotherapy

9-ING-41 DRUG

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

Also known as: Elraglusib

Retifanlimab + 9-ING-41 + Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 radiation on a subsequent scan prior to trial enrollment.
• Must have available archived FFPE tumor tissue at study entry; FFPE tissue block preferred or 10 unstained slides (metastatic tissue preferred to primary tissue) OR if FFPE archived tissue is not available, willing to provide a standard fresh tumor biopsy prior to start of study treatment for molecular profiling of the tumor using standard institutional oncomine panel. If oncomine testing has previously been completed, a repeat biopsy or testing is not required.
• Has laboratory function within specified parameters (may be repeated):
• Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 1,500/mL; hemoglobin ≥ 8.5 g/dL, platelets ≥ 100,000/mL
• Adequate liver function: transaminases (aspartate aminotransferase/ alanine aminotransferase, AST/ALT) and alkaline phosphatase ≤ 2.5 x ULN (≤ 5 X the upper limit of normal (ULN) in the setting of liver metastasis or infiltration with malignant cells); bilirubin ≤ 1.5 x ULN
• Adequate renal function: CrCl \> 60 mL/min measured or calculated by Cockcroft-Gault (C-G) equation (estimated glomerular filtration rate \[eGFR\] can also be used in place of CrCl)
• Serum amylase and lipase ≤ 1.5 x ULN
• Eastern Co-operative Oncology Group (ECOG) performance status (PS) 0 - 1 (Appendix A)
• Has received the final dose of any of the following treatments/ procedures within the specified minimum intervals before first dose of study drug:
• Focal radiation therapy - 7 days
• Surgery with general anesthesia - 7 days
• Surgery with local anesthesia - 7 days

You may not qualify if:

• Is pregnant or lactating.
• Is known to be hypersensitive to any of the components or metabolites of 9-ING-41 or to the excipients used in its formulation, or known sensitivity to one of the chemotherapeutic agents or to the PD-1 inhibitor.
• History of receiving prior treatment with any anti-PD-1, PD-L1 or PD-L2 agent.
• Has endocrine or acinar pancreatic carcinoma.
• Has not recovered from clinically significant toxicities as a result of prior anticancer therapy, except alopecia, anemia not requiring transfusion support and infertility. Recovery is defined as ≤ Grade 1 or baseline severity per Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (v5.0).
• Has significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, or stroke within 6 months of the first dose of 9-ING-41, or cardiac arrhythmia requiring medical treatment detected at screening.
• Has had a myocardial infarction within 12 weeks of the first dose of 9-ING-41 or has electrocardiogram (ECG) abnormalities that are deemed medically relevant by the treating investigator or PI.
• Has symptomatic rapidly progressive brain metastases or leptomeningeal involvement as assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI). Patients with stable brain metastases or leptomeningeal disease or slowly progressive disease are eligible provided that they have not required new treatments for this disease in a 28-day period before the first dose of study drug, and anticonvulsants and steroids are at a stable dose for a period of 14 days prior to the first dose of study drug.
• Has had major surgery (not including placement of central lines) within 7 days prior to study entry or is planned to have major surgery during the course of the study (major surgery may be defined as any invasive operative procedure in which an extensive resection is performed, e.g., a body cavity is entered, organs are removed, or normal anatomy is altered). In general, if a mesenchymal barrier is opened (pleural cavity, peritoneum, meninges), the surgery is considered major.
• Has any medical and/or social condition that, in the opinion of the investigator would preclude study participation.
• Has received an investigational anti-cancer drug in the 14-day period before the first dose of study drug (or within 5 half-lives if longer) or is currently participating in another interventional clinical trial.
• Has a current malignancy other than pancreatic cancer.
• Known immunodeficiency syndrome or active autoimmune disease or requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (\> 10 mg/day of prednisone or equivalent).
• Physiologic corticosteroid replacement therapy at doses \> 10 mg/day of prednisone or equivalent for adrenal or pituitary insufficiency and in the absence of active autoimmune disease is permitted.
• Participants with asthma that requires intermittent use of bronchodilators, inhaled steroids, or local steroid injections may participate.

Sponsors & Collaborators

• Anwaar Saeed: lead
• Actuate Therapeutics Inc.: collaborator
• Incyte Corporation: collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

MeSH Terms

Conditions

Hereditary Sensory and Autonomic Neuropathies

Interventions

Drug Therapy; 3-(5-fluorobenzofuran-3-yl)-4-(5-methyl-5H-(1,3)dioxolo(4,5-f)indol-7-yl)-pyrrole-2,5-dione

Condition Hierarchy (Ancestors)

Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Anwaar Saeed, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Debra Diecks, BSN

CONTACT

412-623-8364; diecksda@upmc.edu

Amy Rose, BSN

CONTACT

412-647-8587; kennaj@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor & Chief of GI Medical Oncology

Study Record Dates

• First Submitted: March 18, 2025
• First Posted: March 26, 2025
• Study Start: September 22, 2025
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: September 29, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)