9-ING-41 Plus Retifanlimab and Gemcitabine/Nab-Paclitaxel in Patients With Advanced Pancreatic Adenocarcinoma

NCT05239182 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: HCC 22-194
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

Brief Summary

This trial examines how Pancreatic Adenocarcinoma reacts to the addition of 9-ING-41 and retifanlimab to the standard of care chemotherapy treatment, to see if using this combination will help and is able to effect disease progression.

Conditions

Pancreatic Adenocarcinoma

Keywords

glycogen biosynthesis; Glycogen synthase kinase-3 (GSK-3); NF-κB pathway

Outcome Measures

Primary Outcomes (1)

• Disease Control Rate (DCR)

  Percentage of patients with stable disease (SD), Complete Response (CR), or Partial Response (PR) for ≥16 weeks during treatment. Per RECIST v1.1, (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or nontarget) with reduction in short axis to \<10 mm. (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

  Up to approximately 11 months from baseline

Secondary Outcomes (6)

• Best Response

  Up to 12 months (from enrollment)

• Overall Response Rate (ORR)

  Up to 12 months (from enrollment)

• Adverse Events and Serious Adverse Events

  Up to 12 months (from enrollment)

• Duration of Response (DOR)

  Up to 12 months (from enrollment)

• Progression-free Survival (PFS)

  Up to 12 months (from enrollment)

Study Arms (1)

9-ING-41 plus Retifanlimab plus Gem/Abraxane

EXPERIMENTAL

* intravenous (IV) infusion of nab-paclitaxel at a dose of 125 mg per square meter, followed by an infusion of gemcitabine according to the gemcitabine label at a dose of 1000 mg per square meter, on days 1, 8, 15 of a 28-day cycle. * Retifanlimab 500 mg IV on day 1 of a 28-day cycle. (Retifanlimab will be administered following gemcitabine/nab-paclitaxel.) * 9-ING-41 administered at a dose of 9.3 mg/kg by IV infusion twice weekly on Days 1 and 4 of each week of a 28-day cycle. (9-ING-41 will be administered following retifanlimab.)

Drug: 9-ING-41; Drug: Retifanlimab; Drug: Gemcitabine; Drug: Abraxane

Interventions

9-ING-41 DRUG

9-ING-41 is a small molecule potent selective GSK-3β inhibitor

9-ING-41 plus Retifanlimab plus Gem/Abraxane

Retifanlimab DRUG

Humanized, hinge-stabilized, IgG4κ monoclonal antibody that recognizes human PD-1.

Also known as: INCMGA00012

9-ING-41 plus Retifanlimab plus Gem/Abraxane

Gemcitabine DRUG

cytotoxic chemotherapy agent

9-ING-41 plus Retifanlimab plus Gem/Abraxane

Abraxane DRUG

cytotoxic chemotherapy agent

9-ING-41 plus Retifanlimab plus Gem/Abraxane

Eligibility Criteria

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

You may qualify if:

• Voluntarily written informed consent and willingness/ability to comply with the protocol requirements
• 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 tumor tissue at study entry (metastatic tissue preferred to primary tissue)
• Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 1000/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: creatinine clearance 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
• 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 investigator or study medical coordinator.
• 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).
• 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).
• Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis.
• Palliative radiation therapy administered within 1 week of first dose of study treatment or radiation therapy that is \> 30 Gy within 6 months of the first dose of study treatment.

Sponsors & Collaborators

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

Study Sites (2)

Kansas University Cancer Center

Fairway, Kansas, 66205, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (1)

• Shaw G, Cavalcante L, Giles FJ, Taylor A. Elraglusib (9-ING-41), a selective small-molecule inhibitor of glycogen synthase kinase-3 beta, reduces expression of immune checkpoint molecules PD-1, TIGIT and LAG-3 and enhances CD8+ T cell cytolytic killing of melanoma cells. J Hematol Oncol. 2022 Sep 14;15(1):134. doi: 10.1186/s13045-022-01352-x.

  PMID: 36104795 DERIVED

MeSH Terms

Interventions

3-(5-fluorobenzofuran-3-yl)-4-(5-methyl-5H-(1,3)dioxolo(4,5-f)indol-7-yl)-pyrrole-2,5-dione; Gemcitabine; Albumin-Bound Paclitaxel

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Barbara Stadterman, MPH, CCRP, Clinical Research Manager
• Organization: UPMC Hillman Cancer Center

stadtermanbm@upmc.edu

4126475554

Study Officials

• Anwaar Saeed, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 26, 2022
• First Posted: February 14, 2022
• Study Start: January 26, 2022
• Primary Completion: December 20, 2022
• Study Completion: February 4, 2024
• Last Updated: July 17, 2025
• Results First Posted: July 17, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)