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.
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.
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.
Single group
Retifanlimab
Drug(PD-1)-blocking monoclonal antibody
Chemotherapy
Drugoxaliplatin - 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
9-ING-41
Druga 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
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
Disease control rate (DCR) - imRECIST
Stable disease for ≥ 16 weeks, confirmed complete response (CR), or confirmed partial response (PR) during study treatment per Immune-Modified Response Evaluation Criteria in Solid Tumors (imRECIST ). CR: -100% Percent change (from baseline) in sum of the diameters (including measurable new lesions when present); PR: CR + ≤ 30% change from baseline; SD: \> 30% to \< +20% change from baseline.
Disease control rate (DCR) - RECIST v1.1
Stable disease for ≥ 16 weeks, confirmed complete response (CR), or confirmed partial response (PR) during study treatment. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) Complete Response (CR) is disappearance of all target and non-target lesions; Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters; Stable Disease (SD) is neither sufficient decrease (target lesions) to qualify as a PR or sufficient increase to qualify as PD. Incomplete Response/Stable Disease (SD) is the persistence of one or more non-target lesions.
Objective response rate (ORR)
Percent of patients with CR or PR imRECIST. Per Immune-Modified Response Evaluation Criteria in Solid Tumors (imRECIST ). CR: -100% Percent change (from baseline) in sum of the diameters (including measurable new lesions when present); PR: CR + ≤ 30% change from baseline.
Duration of response (DOR)
Time from documentation of tumor response to disease progression imRECIST. Per Immune-Modified Response Evaluation Criteria in Solid Tumors (imRECIST ). CR: -100% Percent change (from baseline) in sum of the diameters (including measurable new lesions when present); PR: CR + ≤ 30% change from baseline.
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Anwaar Saeed
Lead sponsor
University of Pittsburgh
Sponsor institution
Actuate Therapeutics Inc.
Collaborator
Incyte Corporation
Collaborator
