Genetically Modified T-Cells for Pancreatic Cancer

Overseen By IMTX Intake Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Fred Hutchinson Cancer Center

Must not be taking: Corticosteroids, Investigational agents

Disqualifiers: Pregnancy, Autoimmune disease, Organ transplant, others

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

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment using genetically modified T-cells to target pancreatic cancer that has metastasized. The treatment, known as Autologous Mesothelin-specific TCR-T Cells, uses the patient's own T-cells, enhanced to better recognize and attack cancer cells. Participants will also receive chemotherapy drugs to help the modified T-cells work more effectively against the cancer. The trial seeks individuals with metastatic pancreatic cancer who have previously undergone chemotherapy and have measurable tumors. The researchers aim to determine the safest dose and possible side effects of this new approach. 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 innovative therapy.

Do I have to stop taking my current medications for the trial?

Participants must be at least 3 weeks from their last systemic treatment for metastatic disease, which includes immunotherapy, chemotherapy, and other investigational agents. There is no washout period for radiation, but certain medications like RANK-ligand inhibitors are not allowed within 8 weeks of treatment. 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 continues to explore the safety of using mesothelin-specific T-cells in patients with advanced pancreatic cancer. In earlier studies, some patients received this treatment, and researchers closely observed their responses.

Early results indicate that researchers are monitoring the treatment for side effects. Some patients might experience reactions because these T-cells target specific cancer cells. However, the treatment remains in early testing stages, primarily to determine potential side effects and safe dosage.

This treatment is not yet approved for general use in pancreatic cancer patients. The trial is in its initial phase, involving a small number of participants to ensure safety before expanding to larger groups. While researchers remain hopeful, they continue to gather crucial safety information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the use of genetically modified T-cells for pancreatic cancer because they introduce a novel approach to treatment by using autologous mesothelin-specific TCR-T cells. Unlike traditional treatments like chemotherapy and radiation, which target cancer cells broadly and often harm healthy cells, these T-cells are engineered to specifically recognize and attack cancer cells expressing the mesothelin protein. This targeted mechanism has the potential to enhance the effectiveness of the treatment while minimizing damage to non-cancerous cells, potentially leading to fewer side effects. Additionally, this approach represents a personalized form of therapy, as it uses the patient's own immune cells, potentially increasing the treatment's efficacy.

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

Research has shown that targeting mesothelin, a protein often found in large amounts on pancreatic cancer cells, can be an effective treatment approach. In this trial, participants will receive genetically modified T cells engineered to specifically target mesothelin. These T cells assist the immune system in identifying and destroying cancer cells. Early results suggest that these modified T cells can remain in the body, stay active, and effectively detect and attack cancer cells. In the various treatment arms of this trial, these T cells are combined with chemotherapy drugs, potentially enhancing their ability to kill more cancer cells. These initial findings offer a hopeful outlook for treating advanced pancreatic cancer using this method. ^{1 2 3 4 6}

Who Is on the Research Team?

Elena Chiorean

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

Adults with metastatic pancreatic ductal adenocarcinoma who've had at least one systemic therapy can join. They must have a life expectancy over 3 months, be willing to undergo tumor biopsies, and not have received recent treatments that could interfere. Participants need properly functioning major organs, no severe autoimmune diseases or organ transplants, and agree to use contraception.

Inclusion Criteria

I have had at least one treatment for cancer that has spread.

Estimated glomerular filtration rate (eGFR) > 60 mL/min

Total bilirubin (bili) =< 1.5 X ULN. Patients with suspected Gilbert syndrome may be included if total bili > 3 mg/dL but no other evidence of hepatic dysfunction

Exclusion Criteria

Concurrent use of other investigational anti-cancer agents

Active autoimmune disease

I currently have an infection that isn't under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion Chemotherapy

Patients receive cyclophosphamide and fludarabine intravenously on days -5, -4, and -3 or optionally bendamustine on days -4 and -3 prior to the first T cell infusion

1 week

3 visits (in-person)

T-Cell Therapy

Patients receive FH-TCR-Tᴍsʟɴ intravenously over 60-120 minutes on days 0, 21, and 42 in the absence of disease progression or unacceptable toxicity

6 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Mesothelin-specific TCR-T Cells

Trial Overview The trial is testing FH-TCR-Tᴍsʟɴ T-cells designed to target mesothelin on cancer cells combined with chemotherapy drugs like cyclophosphamide and fludarabine. The goal is to find the safest dose that helps these modified T-cells better attack the tumor cells in patients with advanced pancreatic cancer.

How Is the Trial Designed?

Group I: Cohorts I, II, and III (FH-TCR Tᴍsʟɴ) Experimental Treatment 4 Interventions

LYMPHODEPLETION CHEMOTHERAPY: Patients receive cyclophosphamide IV and fludarabine IV on days -5, -4 and -3 or may optionally receive bendamustine IV on days -4 and -3 prior to the 1st T cell infusion. T-CELL THERAPY: Patients receive FH-TCR-Tᴍsʟɴ IV over 60-120 minutes on days 0, 21, and 42 in the absence of disease progression or unacceptable toxicity.

Group II: Cohort IV (FH-TCR Tᴍsʟɴ) (Discontinued with amendment 3/28/23) Experimental Treatment 3 Interventions

LYMPHODEPLETION CHEMOTHERAPY: Patients receive cyclophosphamide IV and fludarabine IV on days -3 to -1. T-CELL THERAPY: Patients receive FH-TCR-Tᴍsʟɴ IV over 60-120 minutes on days 0, 21, and 42 in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

Fred Hutchinson Cancer Research Center

Lead Sponsor

Trials

444

Recruited

148,000+

Lonza Walkersville, Inc.

Industry Sponsor

Trials

1

Recruited

9+

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.4_suppl.TPS779

FH-TCR T MSLN ) in patients with metastatic pancreatic ... We developed an autologous TCR-T cell therapy targeting MSLN, which is overexpressed by 80% of PDAs. In this first-in-human phase I trial, we seek to determine ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04809766

NCT04809766 | Mesothelin-Specific T-Cells (FH-TCR- ... This phase I trial evaluates the side effects and best dose of mesothelin-specific T-cells in treating patients with pancreatic ductal adenocarcinoma that ...

3. aacrjournals.org aacrjournals.org/cancerres/article/84/2_Supplement/A003/732865/Abstract-A003-Preliminary-safety-results-from-a

Abstract A003: Preliminary safety results from a phase I study ... In this first-in-human phase I trial, we are determining safety, preliminary efficacy, as well as persistence, activation, localization, and functional capacity

4. asco.org asco.org/posters/POSTER394140

Phase I study of autologous transgenic T cells expressing ... Two phase I/II open label clinical trials evaluating the safety and efficacy of autologous T cells expressing enhanced TCRs ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29567081/

Activity of Mesothelin-Specific Chimeric Antigen Receptor T ... We performed a phase I study to evaluate the safety and efficacy of adoptive cell therapy with autologous mesothelin-specific CAR T cells (CARTmeso cells) in 6 ...

6. researchgate.net researchgate.net/publication/377450303_Abstract_A003_Preliminary_safety_results_from_a_phase_I_study_of_autologous_transgenic_T_cells_expressing_high_affinity_mesothelin-specific_T_cell_receptor_TCR_FH-TCR_TMSLN_in_patients_pts_with_metast

Abstract A003: Preliminary safety results from a phase I ... Preliminary safety results from a phase I study of autologous transgenic T cells expressing high affinity mesothelin-specific T cell receptor (TCR) (FH-TCR ...