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

(RiLEY Trial)

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

32 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment that adds two drugs to standard chemotherapy for advanced pancreatic cancer. The new drugs aim to help the immune system fight cancer more effectively. This treatment is for patients with a severe form of pancreatic cancer that may not respond well to standard treatments alone.

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.

What data supports the effectiveness of the drug 9-ING-41 + Immunotherapy + Chemotherapy for Pancreatic Cancer?

Research shows that the combination of nab-paclitaxel (Abraxane) and gemcitabine has improved survival rates in patients with advanced pancreatic cancer. This suggests that combining these drugs with other treatments, like 9-ING-41, could potentially enhance effectiveness. ^{1 2 3 4 5}

Is the combination of 9-ING-41, immunotherapy, and chemotherapy safe for humans?

The combination of nab-paclitaxel (Abraxane) and gemcitabine has been shown to have an acceptable safety profile in patients with advanced pancreatic cancer, indicating it is generally safe for human use. ^{3 4 5 6 7}

What makes the drug 9-ING-41 + Immunotherapy + Chemotherapy unique for pancreatic cancer?

This treatment combines 9-ING-41, a GSK-3β inhibitor, with immunotherapy and chemotherapy, which is different from standard treatments that typically use only chemotherapy drugs like nab-paclitaxel (Abraxane) and gemcitabine. The inclusion of 9-ING-41 and retifanlimab (an immunotherapy drug) aims to enhance the treatment's effectiveness by targeting cancer cells in multiple ways. ^{3 4 5 6 8}

Research Team

Anwaar Saeed

Principal Investigator

University of Pittsburgh

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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 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]

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]

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]

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]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[Nab-Paclitaxel plus Gemcitabine Hydrochloride in Patients with Metastatic or Recurrent Pancreatic Cancer - A Single Institution Experience]. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Adjuvant nab-paclitaxel plus gemcitabine vs gemcitabine alone for resected pancreatic ductal adenocarcinoma: A single center experience in China. [2020]

3. England pubmed.ncbi.nlm.nih.gov

A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus nab-Paclitaxel and Gemcitabine in Advanced Solid Tumors. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Nursing Implications of Chemotherapy Agents and Their Associated Side Effects in Patients With Pancreatic Cancer. [2017]

7. England 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. [2023]

8. Germany 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. [2022]