9-ING-41 + Retifanlimab + Chemotherapy for Pancreatic Cancer

(RiLEY Trial)

Overseen By Amy Rose, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Anwaar Saeed

Must not be taking: Anti-PD-1 agents

Disqualifiers: Pregnancy, Cardiovascular impairment, Brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 14

Duration: Up to 24 months

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This clinical trial tests a new combination of drugs for individuals with advanced pancreatic cancer. The goal is to determine if 9-ING-41 (an experimental treatment) and Retifanlimab (an immunotherapy drug), when combined with standard chemotherapy, are safe and effective. Participants should have pancreatic cancer that has not previously been treated with chemotherapy for advanced stages. The trial will begin with a few patients to ensure safety and may adjust doses based on results. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must not be receiving any other investigational medicinal product and should not have received systemic antibiotics within 7 days prior to the first dose of the study drug.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that 9-ING-41, also known as elraglusib, has been tested for safety in other studies. Some patients experienced more side effects when combined with other cancer treatments, leading to an adjusted dose of 9.3 mg/kg twice a week.

Retifanlimab is an immune therapy that blocks PD-1, a protein that can prevent the immune system from attacking cancer cells. It has been used to treat certain skin and anal cancers. The side effects are typical for this kind of treatment, expected but manageable, and can vary among individuals.

Both treatments have been studied previously, providing some information about their safety. However, as this is an early-phase trial, the primary goal is to closely monitor and understand the safety and tolerability of using them together for pancreatic cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about 9-ING-41 combined with Retifanlimab for pancreatic cancer because it targets the disease in new ways that current treatments don't. While standard treatments like FOLFIRINOX rely on conventional chemotherapy, 9-ING-41 is a GSK-3β inhibitor, which may disrupt cancer cell survival pathways, making it harder for tumors to grow. Retifanlimab is an immune checkpoint inhibitor that helps the immune system better recognize and attack cancer cells. This combination offers a unique approach by potentially halting cancer growth and boosting the body's own defenses against the disease.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

In this trial, participants will receive a combination of 9-ING-41, Retifanlimab, and chemotherapy. Research has shown that 9-ING-41, a drug targeting a protein linked to cancer growth, may help overcome resistance to standard chemotherapy in pancreatic cancer. Studies have found that this drug, when combined with Retifanlimab, could enhance the effectiveness of chemotherapy. Retifanlimab is known to assist the immune system in fighting cancer. Early findings suggest that using these treatments together might improve outcomes for pancreatic cancer patients. By attacking the cancer in several ways, this combination aims to be more effective than standard treatments alone. ^{6 7 8 9 10}

Who Is on the Research Team?

Anwaar Saeed, MD

Principal Investigator

UPMC Hillman Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with advanced pancreatic adenocarcinoma who haven't had systemic therapy before. It's a small study, starting with 6 people to check safety, and may include up to 12 participants after initial assessments.

Inclusion Criteria

I can provide a tissue sample for the study, either from previous surgery or a new biopsy.

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, Surgery with general anesthesia, Surgery with local anesthesia, May have received treatment with fluorouracil or gemcitabine as a radiation sensitizer in the adjuvant setting if the treatment was received at least 6 months before study enrollment, May have received neoadjuvant chemotherapy with FOLFIRINOX if given at least 6 months before study enrollment, May have received prior cytotoxic doses of systemic chemotherapy in the adjuvant setting if given at least 6 months before study enrollment, Women of childbearing potential must have a negative baseline blood or urine pregnancy test within 72 hours of first study therapy, Male patients with partners of childbearing potential must take appropriate precautions to avoid fathering a child from screening until 6 months after discontinuation of study treatment and use appropriate barrier contraception or true abstinence, Must not be receiving any other investigational medicinal product.

My blood, liver, kidney tests are normal, and I can do all my daily activities.

Exclusion Criteria

Has any medical and/or social condition that, in the opinion of the investigator would preclude study participation.

Known hypersensitivity to another monoclonal antibody that cannot be controlled with standard measures.

Is pregnant or lactating.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 9-ING-41, retifanlimab, and mFOLFIRINOX chemotherapy

Up to 24 months

IV infusions every 14 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

Up to 42 months

What Are the Treatments Tested in This Trial?

Interventions

• 9-ING-41
• Retifanlimab

Trial Overview The trial tests a combination of the drug elraglusib (9-ING-41) and retifanlimab with modified FOLFIRINOX chemotherapy. The focus is on finding a safe dose level through an initial cohort and then expanding to more patients if it's deemed safe.

How Is the Trial Designed?

Group I: Retifanlimab + 9-ING-41 + Chemotherapy Experimental Treatment 3 Interventions

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

Who Is Running the Clinical Trial?

Anwaar Saeed

Lead Sponsor

Trials

5

Recruited

240+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Actuate Therapeutics Inc.

Industry Sponsor

Trials

10

Recruited

580+

Published Research Related to This Trial

A multidisciplinary approach using Vedolizumab effectively treated corticosteroid-refractory immune-mediated colitis in a melanoma patient receiving anti-PD-1 therapy, highlighting a potential new treatment strategy for managing immune-related adverse events.

The patient's expression of HLA-B*35 suggests a genetic predisposition to autoimmune reactions, indicating that genotyping may help tailor immunotherapy and manage side effects in high-risk melanoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autoimmune colitis and neutropenia in adjuvant anti-PD-1 therapy for malignant melanoma: efficacy of Vedolizumab, a case report. d'Apolito, M., Spagnuolo, R., Siciliano, MA., et al.[2022]

In a phase II trial involving 48 patients with gemcitabine-refractory unresectable pancreatic cancer, modified FOLFIRINOX demonstrated promising efficacy with an objective response rate of 18.8% and a disease control rate of 62.5%.

The treatment was associated with manageable safety concerns, primarily neutropenia (64.6% of patients), but most non-hematologic adverse events were mild, indicating that while effective, careful monitoring for hematologic toxicities is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase II trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer. Chung, MJ., Kang, H., Kim, HG., et al.[2020]

The combination of gemcitabine, capecitabine, bevacizumab, and erlotinib showed promising efficacy in treating advanced pancreatic cancer, with 10 partial responses observed among 20 patients and median overall survival of 12.5 months.

The maximum-tolerated dose of capecitabine was determined to be 1,660 mg/m², with a recommended dose of 1,440 mg/m² for further studies, while the treatment was generally well-tolerated with manageable side effects like diarrhea and skin rash.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose finding and early efficacy study of gemcitabine plus capecitabine in combination with bevacizumab plus erlotinib in advanced pancreatic cancer. Starling, N., Watkins, D., Cunningham, D., et al.[2022]

A meta-analysis of 53 trials involving 6581 patients revealed that combined immune checkpoint inhibitors (ICIs) lead to significant gastrointestinal adverse events, with diarrhea occurring in 25.4% of patients, hepatitis in nearly 13%, and pancreatitis in about 7.5%.

The study highlights a high incidence of both mild and severe gastrointestinal adverse events associated with combined ICI treatments, indicating a need for further research to understand these effects and their impact on patient treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal treatment-related adverse events of combined immune checkpoint inhibitors: a meta-analysis. Karna, R., S Deliwala, S., Ramgopal, B., et al.[2023]

In a phase 3 study involving 800 patients with metastatic pancreatic cancer, ganitumab combined with gemcitabine did not improve overall survival (OS) compared to gemcitabine alone, with median OS of 7.2 months for placebo and similar results for both ganitumab doses (7.0 and 7.1 months).

The combination treatment showed manageable safety with no unexpected toxicities, but circulating biomarkers did not indicate any treatment effect on OS or progression-free survival (PFS).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3 randomized, double-blind, placebo-controlled trial of ganitumab or placebo in combination with gemcitabine as first-line therapy for metastatic adenocarcinoma of the pancreas: the GAMMA trial. Fuchs, CS., Azevedo, S., Okusaka, T., et al.[2022]

In a case series of seven patients treated with immune checkpoint inhibitors (ICIs), two developed diabetic ketoacidosis (DKA) and five experienced pancreatitis, highlighting the potential for serious pancreatic adverse events associated with ICI therapy.

Pancreatitis was often asymptomatic and could be managed effectively by holding the ICI treatment and administering steroids, with some patients able to safely resume ICI therapy after recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancreatic adverse events in patients treated with immune checkpoint inhibitors. Hana, C., Rehman, T., Park, K., et al.[2023]

In a study of 184 patients with non-small cell lung cancer treated with immune checkpoint inhibitors, 26.6% developed immune-related adverse events (IRAEs), with certain factors like statin use and previous corticosteroid therapy increasing the risk of IRAEs.

Interestingly, patients who experienced IRAEs had significantly better progression-free survival (41 weeks vs. 9 weeks) and overall survival (89 weeks vs. 28 weeks), suggesting that the occurrence of IRAEs may be linked to improved treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of immune-related adverse events and outcomes in patients with NSCLC treated with immune-checkpoint inhibitors. Serino, M., Freitas, C., Martins, M., et al.[2022]

In a phase I trial involving 50 patients with advanced pancreatic cancer, the combination of nivolumab, nab-paclitaxel, and gemcitabine showed a manageable safety profile, with 48 patients experiencing grade 3/4 treatment-emergent adverse events, but only one dose-limiting toxicity reported.

The treatment resulted in a median overall survival of 9.9 months and an overall response rate of 18%, indicating limited efficacy, which led to the conclusion that further investigation of this combination is not supported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label, Phase I Study of Nivolumab Combined with nab-Paclitaxel Plus Gemcitabine in Advanced Pancreatic Cancer. Wainberg, ZA., Hochster, HS., Kim, EJ., et al.[2022]

In a systematic review of 59 randomized controlled trials involving 41,757 patients, immune checkpoint inhibitors (ICIs) were found to be associated with a 0.93% incidence of all-grade pancreatitis and higher rates of pancreatic enzyme elevations, indicating a notable risk of pancreatic adverse events (AEs) during treatment.

The study revealed that PD-1 inhibitors carry a greater risk of pancreatic AEs compared to PD-L1 inhibitors, and patients receiving dual ICI therapy face an even higher risk than those on single ICI therapy, highlighting the need for clinician awareness regarding these potential complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancreatic adverse events of immune checkpoint inhibitors therapy for solid cancer patients: a systematic review and meta-analysis. Zhao, Z., Zhang, W., Pang, L., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06896188

NCT06896188 | 9-ING-41 Combined With Retifanlimab ... 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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05239182

Study Details | NCT05239182 | 9-ING-41 Plus Retifanlimab ... 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 ...

3. kucancercenter.org kucancercenter.org/cancer-clinical-trials/find-trial/clinical-trial-results/nct05239182

A Phase II Study of 9-ING-41 GSK-3? Combined with ... A Phase II Study of 9-ING-41 GSK-3? Combined with Retifanlimab plus Gemcitabine/Nab-Paclitaxel as Frontline Therapy for Patients with Advanced Pancreatic ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8301062/

GSK-3β in Pancreatic Cancer: Spotlight on 9-ING-41, Its ... Studies show targeting this protein for treatment may overcome resistance to conventional chemotherapy in pancreatic tumors. Early-stage ...

5. withpower.com withpower.com/trial/phase-1-adenocarcinoma-4-2025-b4913

9-ING-41 + Retifanlimab + Chemotherapy for Pancreatic ... This is a study of the combination of 9 ING-41 (elraglusib) and retifanlimab plus mFOLFIRINOX in patients with pancreatic cancer without prior systemic ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40403387/

Phase II study of elraglusib (9-ING-41), a GSK-3β inhibitor ... In terms of safety, elraglusib resulted in a modest exacerbation of GnP-related toxicities, leading to a dose reduction of elraglusib to 9.3 mg/kg twice a week.

7. esmoopen.com esmoopen.com/article/S2059-7029(25)00991-3/fulltext

Phase II study of elraglusib (9-ING-41), a GSK-3β inhibitor ... The purpose of this study was to assess the efficacy and safety of elraglusib (9-ING-41), a GSK-3β inhibitor, in combination with gemcitabine/ ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03678883

NCT03678883 | 9-ING-41 in Patients with Advanced Cancers 9-ING-41 has significant in vitro and in vivo activity as a single agent and/or in combination with standard cytotoxic chemotherapies in a spectrum of solid ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.4_suppl.578

Phase 2 study of 9-ING-41, a small molecule selective ... 9-ING-41 has significant anti-tumor activity through apoptosis induction, anti-fibrotic activity and NK/T-cell effector stimulation.

10. mayo.edu mayo.edu/research/clinical-trials/cls-20456372

A Study of 9-ING-41 in Patients with Advanced Cancers The purpose of this study is to evaluate the safety and effectiveness of 9-ING-41, a potent GSK-3β inhibitor, as a single agent and in combination with ...