What side effects are associated with this type of intervention?

Genetically modified T-cell therapies for pancreatic cancer, such as mesothelin-specific T-cells (FH-TCR-Tᴍsʟɴ), can cause side effects including cytokine release syndrome, which may result in fever, fatigue, and multiorgan dysfunction, including acute kidney injury. Other potential side effects include electrolyte abnormalities, immune-related adverse events like acute tubulointerstitial nephritis, and general chemotherapy-related toxicities such as nausea, vomiting, and myelosuppression.

What prior FDA approvals exist?

The FDA has approved several treatments for pancreatic cancer, including chemotherapy regimens like FOLFIRINOX (a combination of leucovorin, fluorouracil, irinotecan, and oxaliplatin) and gemcitabine-based therapies. While there are no specific FDA approvals for genetically modified T-cell therapies targeting mesothelin in pancreatic cancer, similar approaches in other cancers include CAR-T cell therapies targeting CD19 in hematologic malignancies. These therapies involve modifying a patient's T-cells to better recognize and attack cancer cells, akin to the investigational mesothelin-specific T-cells (FH-TCR-Tᴍsʟɴ) being studied for metastatic pancreatic ductal adenocarcinoma.

What other types of research exist?

Promising novel alternatives to Mesothelin-specific T-cells (FH-TCR-Tᴍsʟɴ) for pancreatic cancer patients include: 1) Immune checkpoint inhibitors such as pembrolizumab (anti-PD-1) and nivolumab (anti-PD-1), which have shown efficacy in various cancers and are being explored in pancreatic cancer. 2) CAR-T cell therapies targeting other antigens like Claudin 18.2, which is overexpressed in pancreatic cancer cells. 3) Bispecific antibodies that can engage T-cells to target pancreatic cancer cells, such as those targeting CD3 and a tumor-specific antigen. 4) Oncolytic virotherapy, which uses genetically modified viruses to selectively infect and kill cancer cells while stimulating an anti-tumor immune response.

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CAR T-cell Therapy

Genetically Modified T-Cells for Pancreatic Cancer

Phase 1

Recruiting

Led By Elena G. Chiorean

Research Sponsored by Fred Hutchinson Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Tumor tissue amenable to safe biopsy and subject willing to undergo serial tumor biopsies

Serum creatinine =< 1.5 x upper limit of normal (ULN) or estimated glomerular filtration rate (eGFR) > 60 mL/min

Must not have

Active uncontrolled infection

Prior solid organ transplant or allogeneic hematopoietic stem cell transplant

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 4 weeks after the last t cell infusion

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new treatment for advanced pancreatic cancer using modified immune cells from the patient. These cells are changed to better recognize and attack cancer cells. The goal is to find the best dose and see if this approach can help patients whose cancer has spread.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include reactions related to immune system activation such as inflammation in different body parts, symptoms from cell infusion like fever or chills, and typical chemotherapy-related issues such as nausea, fatigue, low blood counts increasing infection risk.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am willing and able to have multiple biopsies of my tumor.

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My kidney function, measured by creatinine or eGFR, is within the normal range.

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My HLA type is HLA-A*02:01.

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It has been over 3 weeks since my last treatment for cancer that has spread.

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I have undergone chemotherapy before.

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My pancreatic cancer has spread and tests show it has mesothelin.

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My pancreatic cancer is confirmed and shows mesothelin expression.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I am 18 years old or older.

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I have mild or no shortness of breath and my oxygen levels are above 92% without extra oxygen.

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I have at least two measurable cancer lesions confirmed by recent scans.

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My HLA type is HLA-A*02:01, suitable for the T cell therapy.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I have had a solid organ or bone marrow transplant.

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I am currently being treated for side effects from previous immunotherapy.

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I have brain metastases that have not been treated.

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My genetic test shows I have HLA B*1302.

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I am taking a high dose of steroids daily.

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I need frequent drainage for fluid buildup in my chest or abdomen.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 4 weeks after the last t cell infusion

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 4 weeks after the last t cell infusion

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 4 weeks after the last t cell infusion for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of adverse events

Secondary study objectives

Overall response rate

Overall survival

Progression free survival

Side effects data

From 2023 Phase 2 trial • 27 Patients • NCT04002401

88%

Pyrexia

65%

Neutrophil count decreased

62%

Nausea

58%

Hypotension

50%

Anaemia

46%

Headache

38%

Fatigue

38%

Decreased appetite

35%

Confusional state

31%

Tachycardia

31%

Diarrhoea

31%

Hypokalaemia

27%

Constipation

27%

Hypophosphataemia

27%

Back pain

23%

Dizziness

23%

Tremor

23%

B-cell lymphoma

23%

Platelet count decreased

23%

White blood cell count decreased

19%

Cough

19%

Agitation

19%

Hyponatraemia

19%

Neutropenia

19%

Tachypnoea

19%

Hypogammaglobulinaemia

19%

Oedema peripheral

15%

Thrombocytopenia

15%

Dysphagia

15%

Alanine aminotransferase increased

15%

Sinus tachycardia

15%

Chills

15%

Dyspnoea

15%

Hypomagnesaemia

12%

Aspartate aminotransferase increased

12%

Pain

12%

Arthralgia

12%

Myalgia

12%

Vomiting

12%

Hypertension

12%

Abdominal pain

12%

Hyperglycaemia

12%

Hypoxia

12%

Peripheral sensory neuropathy

12%

Covid-19

12%

Malaise

Muscular weakness

Dysuria

Blood creatinine increased

Hyperhidrosis

Insomnia

Encephalopathy

Lymphocyte count decreased

Sepsis

Pancytopenia

Asthenia

Eye pain

Urinary tract infection

Acute myeloid leukaemia

Somnolence

Oral candidiasis

Pneumonia

Gait disturbance

Aphasia

Depression

Syncope

Embolism

Pleural effusion

Respiratory failure

Febrile neutropenia

Covid-19 pneumonia

100%

80%

60%

40%

20%

Study treatment Arm

Axicabtagene Ciloleucel and Rituximab Combination

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Cohorts I, II, and III (FH-TCR Tᴍsʟɴ)Experimental Treatment4 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 Treatment3 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cyclophosphamide

2010

Completed Phase 4

~2310

Bendamustine

2015

Completed Phase 3

~3230

Fludarabine

2012

Completed Phase 4

~1860

0 / 19Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for pancreatic cancer include chemotherapy, targeted therapy, and immunotherapy. Chemotherapy drugs like cyclophosphamide and fludarabine work by killing rapidly dividing tumor cells or stopping their growth. Targeted therapies, such as those inhibiting specific mutations like KRAS G12C, aim to block pathways essential for cancer cell survival. Immunotherapy, including mesothelin-specific T-cells (FH-TCR-Tᴍsʟɴ), involves genetically modifying a patient's T-cells to recognize and kill tumor cells expressing mesothelin, a protein overexpressed in pancreatic cancer. This approach is significant for pancreatic cancer patients as it offers a personalized treatment option that harnesses the body's immune system to target and eliminate cancer cells, potentially leading to more effective and durable responses.