iExosomes for Pancreatic Cancer

Overseen By Brandon Smaglo, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Uncontrolled diabetes, CNS disease, others

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

Compensation: Varies

Number of Visits: 33

Duration: 6 weeks

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the best dose and assess the side effects of a new treatment called iExosomes for individuals with advanced pancreatic cancer. iExosomes are tiny particles derived from mesenchymal stromal cells that may target and fight pancreatic cancer more effectively. The treatment is intended for those whose cancer has spread and who have a specific genetic mutation called KrasG12D. It suits individuals who have undergone at least four months of chemotherapy without improvement. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does mention that patients with stable disease must have completed at least 4 months of chemotherapy, which might imply continuing some treatments. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that iExosome therapy, which uses tiny particles from special cells to deliver specific genetic material, is generally safe and well-tolerated in humans. Earlier studies found that these treatments caused little to no harm. Designed to specifically target the pancreas, this approach is important for treating pancreatic cancer. Initial results suggest that this method effectively reaches its target, indicating it might work well without causing major side effects. Overall, although still in early testing, the treatment has shown promise in terms of safety for those considering participation in trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about mesenchymal stromal cells-derived exosomes with KRAS G12D siRNA because it takes a novel approach to treating pancreatic cancer. Unlike traditional treatments like chemotherapy and radiation, which attack cancer cells broadly, this treatment specifically targets the KRAS G12D mutation, a common driver of pancreatic cancer. This targeted approach could potentially minimize side effects and improve effectiveness. Additionally, using exosomes as a delivery method is innovative, as these tiny vesicles naturally transport molecules between cells, potentially offering a more efficient way to deliver the siRNA directly to cancer cells.

What evidence suggests that this treatment might be an effective treatment for pancreatic cancer?

Research has shown that iExosomes, tiny particles from special cells, are designed to target and silence a specific mutation called KrasG12D, often found in pancreatic cancer. In earlier studies, these engineered particles reached the pancreas, indicating their effectiveness in targeting cancer cells. Importantly, this method caused minimal harm to patients in those studies. Early results also suggest that this treatment is safe and well-tolerated by patients with advanced pancreatic cancer. Overall, the evidence supports the potential of iExosomes to treat pancreatic cancer with the KrasG12D mutation. Participants in this trial will receive mesenchymal stromal cell-derived exosomes with KrasG12D siRNA as part of the treatment. ^{1 2 3 4 6}

Who Is on the Research Team?

Brandon Smaglo, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with metastatic pancreatic cancer that has a specific mutation (KrasG12D). Participants must have tried at least one systemic therapy and have certain blood and organ function levels within normal ranges. Pregnant or breastfeeding individuals are excluded, as well as those with severe medical conditions or brain metastases unless treated and stable.

Inclusion Criteria

I have Gilbert's syndrome with direct bilirubin ≤ 1.5 times the upper limit.

My cancer has either not changed or worsened after treatment.

Your liver enzymes AST and ALT are within a certain normal range.

Exclusion Criteria

You are pregnant or breastfeeding.

I have treated brain metastasis with no current signs of worsening and don't need steroids.

I do not have any severe health issues that could affect my participation in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mesenchymal stromal cells-derived exosomes with KrasG12D siRNA intravenously on days 1, 4, and 10, repeating every 14 days for up to 3 courses

6 weeks

3 visits per course (in-person)

Extended Treatment

Participants who respond may continue 3 additional courses of treatment

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

1 year

Follow-up at 30 days, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Mesenchymal Stromal Cells-derived Exosomes with KRAS G12D siRNA

Trial Overview The trial is testing the safety and optimal dosage of iExosomes—tiny vesicles from mesenchymal stromal cells carrying siRNA targeting the KrasG12D mutation. The goal is to see if they can effectively treat pancreatic cancer that has spread in the body.

How Is the Trial Designed?

Group I: Treatment (iExosomes) Experimental Treatment 1 Intervention

Participants receive mesenchymal stromal cells-derived exosomes with KrasG12D siRNA IV over 15-20 minutes on days 1, 4, and 10. Treatment repeats every 14 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Participants who respond may continue 3 additional courses.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Citations

1. nature.com nature.com/articles/s41467-025-63718-2

Engineered exosomes with Kras G12D specific siRNA in ... Here, we show that engineered exosomes with KrasG12D specific siRNA (iExoKrasG12D) reveal a biodistribution in pancreas with negligible toxicity ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03608631

Study Details | NCT03608631 | iExosomes in Treating ... This phase I trial studies the best dose and side effects of mesenchymal stromal cells-derived exosomes with KrasG12D siRNA (iExosomes) in treating ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.4_suppl.TPS633

derived exosomes with KRAS G12D siRNA in patients ... This is a single arm, single institution, phase I trial evaluating treatment with KRAS G12D -siRNA loaded exosomes.

4. aacrjournals.org aacrjournals.org/cancerres/article/84/2_Supplement/C084/732761/Abstract-C084-iExplore-A-phase-I-study-of

Abstract C084: iExplore: A phase I study of mesenchymal stem ... iExosome therapy targeting Kras G12D is a safe and well-tolerated treatment for metastatic pancreatic cancer.

5. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2018-0126.html

Phase I Study of Mesenchymal Stromal Cells-Derived ... This phase I trial studies the best dose and side effects of mesenchymal stromal cells-derived exosomes with KrasG12D siRNA (iExosomes) in treating participants ...

6. oncodaily.com oncodaily.com/trial-updates/iexplore-krasg12d-sirna-exosomes-pdac

iEXPLORE Trial: KRASG12D siRNA Exosomes in PDAC The iEXPLORE Phase I trial tested exosome therapy with KRASG12D siRNA in advanced pancreatic cancer, showing safety, target engagement.