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

(RiLEY Trial)

No longer recruiting at 2 trial locations

Overseen By KUCC Navigation

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Kansas Medical Center

Must not be taking: Antibiotics, Immunosuppressants

Disqualifiers: Pregnancy, Cardiovascular impairment, Brain metastases, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 28-day cycles, up to 60 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments to determine if they can better control advanced or metastatic pancreatic cancer. It adds two new drugs, 9-ING-41 (a GSK-3β inhibitor) and retifanlimab (an immunotherapy drug), to the usual chemotherapy regimen to see if this mix can slow the disease or make it more manageable. People with pancreatic cancer who have not received strong medication before might be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to potentially groundbreaking advancements in cancer care.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not have received any investigational anti-cancer drugs within 14 days before starting the study drug. It's best to discuss your current medications with the trial team to get a clear answer.

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

Research shows that the treatment combination in this trial has undergone safety studies. Here is a breakdown:

1. **9-ING-41**: This drug might slightly increase the side effects of standard chemotherapy, so researchers adjust the dose. It fights tumors by killing cancer cells and boosting the immune system. It is administered twice a week at a lower dose to manage side effects.

2. **Retifanlimab**: Tested in other studies and approved for some cancers, this immunotherapy has a known safety record. However, it can sometimes cause inflammation in hormone-producing glands, observed in a small number of patients.

3. **Abraxane**: Commonly used in cancer treatment, this chemotherapy can lower white blood cell counts, increasing infection risk. This side effect is known and manageable.

4. **Gemcitabine**: Another standard chemotherapy drug, it generally causes similar blood-related side effects as Abraxane, such as low white blood cells and fatigue.

Overall, these treatments have been used before, and while side effects exist, they are generally manageable. Each drug's safety has been studied, and doses are adjusted to ensure maximum safety. Participants should consult their doctors about potential risks to understand what to expect. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of 9-ING-41, Retifanlimab, Abraxane, and Gemcitabine for pancreatic cancer because it targets the disease in a new way. Unlike standard chemotherapy, which broadly attacks cancer cells, 9-ING-41 is a GSK-3β inhibitor, offering a more targeted approach by disrupting cancer cell growth pathways. Retifanlimab is an immunotherapy that helps the immune system recognize and fight cancer cells, potentially enhancing the effectiveness of the treatment. Together, these treatments may offer a more comprehensive attack on the cancer, possibly improving outcomes compared to current options like chemotherapy alone.

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

In this trial, participants will receive a combination of treatments to evaluate their effectiveness against pancreatic cancer. Research has shown that 9-ING-41, a drug that blocks a specific protein, may enhance the effectiveness of standard chemotherapy by killing cancer cells and boosting the body's immune response. Retifanlimab, another treatment in this trial, aids the immune system in fighting cancer and showed positive results in previous studies, with 55% of patients experiencing some tumor shrinkage. Abraxane (nab-paclitaxel) improves drug delivery to cancer cells and has proven more effective than traditional chemotherapy. Gemcitabine, a chemotherapy drug included in this trial, is generally well-tolerated and has increased survival rates, especially when used with Abraxane. Together, these treatments attack cancer in different ways, aiming to improve outcomes for patients with pancreatic cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Anwaar Saeed

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for adults with advanced, untreated pancreatic cancer who can consent to study procedures. They must have measurable disease, good liver and kidney function, no major surgery or certain treatments within specific time frames before the trial, and a performance status indicating they are relatively active.

Inclusion Criteria

My pancreatic cancer is advanced or has spread, and I haven't received systemic treatment for it.

My liver tests are within the required limits.

I have at least one tumor that can be measured and has not been treated with radiation.

Exclusion Criteria

My brain cancer is stable, and I haven't needed new treatments for it in the last 28 days.

I have had an organ or stem cell transplant.

I have not had a heart attack in the last 3 months and my ECG is normal.

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 gemcitabine/nab-paclitaxel as frontline therapy for advanced pancreatic adenocarcinoma

28-day cycles, up to 60 months

Weekly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 9-ING-41
• Abraxane
• Gemcitabine
• Retifanlimab

Trial Overview The study tests if adding 9-ING-41 and retifanlimab to standard chemotherapy (Gemcitabine/Nab-Paclitaxel) improves outcomes in pancreatic cancer patients. It aims to see if this combination affects how long patients live without their disease getting worse.

How Is the Trial Designed?

Group I: 9-ING-41 plus Retifanlimab plus Gem/Abraxane Experimental Treatment 4 Interventions

* 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.)

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

Anwaar Saeed

Lead Sponsor

Trials

5

Recruited

240+

Actuate Therapeutics Inc.

Industry Sponsor

Trials

10

Recruited

580+

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

Published Research Related to This Trial

Itacitinib, a selective JAK1 inhibitor, combined with nab-paclitaxel and gemcitabine, showed an acceptable safety profile and clinical activity in patients with advanced solid tumors, including pancreatic cancer, with a 24% overall response rate across various doses.

The study indicated that while itacitinib was tolerated at lower doses, treatment-related toxicities such as neutropenia and fatigue were common, leading to dose adjustments; however, the study was terminated early due to negative results from a related phase III trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus nab-Paclitaxel and Gemcitabine in Advanced Solid Tumors. Beatty, GL., Shahda, S., Beck, T., et al.[2022]

In the NAPOLI 3 study involving 770 patients with metastatic pancreatic ductal adenocarcinoma, the NALIRIFOX treatment regimen resulted in a median overall survival of 11.1 months, which was significantly longer than the 9.2 months observed with the nab-paclitaxel and gemcitabine combination.

Both treatment groups experienced a high rate of grade 3 or higher adverse events (87% for NALIRIFOX and 86% for nab-paclitaxel-gemcitabine), indicating that while NALIRIFOX may improve survival, it does not significantly increase the risk of severe side effects compared to the standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. Wainberg, ZA., Melisi, D., Macarulla, T., et al.[2023]

In a study of 27 patients with unresectable pancreatic cancer, nab paclitaxel plus gemcitabine was found to be effective and well-tolerated in elderly patients aged 75 and older, showing similar disease control rates and overall survival compared to younger patients.

Despite a lower relative dose intensity of the drugs in the elderly group, the safety profile was comparable, with neutropenia being the most common severe adverse event, indicating that this treatment regimen can be safely administered to older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of nab paclitaxel plus gemcitabine in elderly patients over 75 years with unresectable pancreatic cancer compared with younger patients. Ishimoto, U., Kinoshita, A., Hirose, Y., et al.[2022]

In a study of 11 patients with metastatic or recurrent pancreatic cancer, the combination of nab-paclitaxel and gemcitabine showed promising efficacy, with a 6-month overall survival rate of 66.7% and a disease control rate of 90.9%.

The treatment was well tolerated, with no treatment-related deaths and manageable side effects, making nab-paclitaxel plus gemcitabine a potential standard treatment for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nab-Paclitaxel plus Gemcitabine Hydrochloride in Patients with Metastatic or Recurrent Pancreatic Cancer - A Single Institution Experience]. Takeda, Y., Katsura, Y., Ohmura, Y., et al.[2022]

In a study of 80 Italian patients with metastatic pancreatic cancer, treatment with nab-paclitaxel in combination with gemcitabine resulted in a median overall survival of 8 months and a median progression-free survival of 5 months, indicating its efficacy.

Nab-paclitaxel was well-tolerated and led to significant pain relief, with reductions in the tumor marker CA 19-9 correlating positively with overall survival, suggesting it may be a useful predictor of treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer. De Luca, R., Blasi, L., Alù, M., et al.[2022]

In a study of patients with resected pancreatic ductal adenocarcinoma (PDAC), adjuvant chemotherapy with nab-paclitaxel plus gemcitabine (AG) significantly improved median disease-free survival (15.8 months) and overall survival (28.3 months) compared to gemcitabine alone (12.2 months and 20.6 months, respectively).

While AG showed better survival outcomes, it also led to a higher incidence of sensory neuropathy (53.3% in AG vs. 23.3% in GEM), indicating a trade-off between efficacy and side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant nab-paclitaxel plus gemcitabine vs gemcitabine alone for resected pancreatic ductal adenocarcinoma: A single center experience in China. Yin, ZZ., Zhao, ZM., Tang, WB., et al.[2020]

Recent treatment regimens for advanced pancreatic cancer, including gemcitabine, FOLFIRINOX, and nab-paclitaxel, have shown varying levels of efficacy, highlighting the importance of understanding their unique safety profiles.

Nurses play a crucial role in patient education and symptom management, as each treatment regimen has different adverse events that need to be identified and managed effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nursing Implications of Chemotherapy Agents and Their Associated Side Effects in Patients With Pancreatic Cancer. Hronek, JW., Reed, M.[2017]

The combination of nab-paclitaxel, gemcitabine, and capecitabine was found to be well tolerated in a phase I study with 15 patients, establishing a maximum-tolerated dose (MTD) but showing only modest antitumor activity in metastatic pancreatic cancer.

Despite the regimen being generally safe, with a low incidence of severe hematologic toxicities, only 14.3% of patients had a partial response, indicating that optimizing dose intensity may be crucial for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. Ko, AH., Truong, TG., Kantoff, E., et al.[2022]

Citations

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

Phase II study of elraglusib (9-ING-41), a GSK-3β inhibitor ... Elraglusib monotherapy led to an objective response rate (ORR) of 3.2%, median progression-free survival (PFS) of 1.6 months, and median overall ...

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

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/nab-paclitaxel ( ...

3. 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.

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. clinicaltrials.gov clinicaltrials.gov/study/NCT03678883

NCT03678883 | 9-ING-41 in Patients with Advanced Cancers The Actuate 1801 Phase 1/2 study is designed to evaluate the safety and efficacy of 9-ING-41, a potent GSK-3β inhibitor, as a single agent and in combination ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03678883

NCT03678883 | 9-ING-41 in Patients with Advanced Cancers The Actuate 1801 Phase 1/2 study is designed to evaluate the safety and efficacy of 9-ING-41, a potent GSK-3β inhibitor, as a single agent and in combination ...