multiTAA Specific T Cells for Pancreatic Cancer

(TACTOPS Trial)

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Baylor College of Medicine

Must not be taking: Systemic corticosteroids

Disqualifiers: Severe infection, HIV, pregnant, others

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

Compensation: Varies

Number of Visits: 7

Duration: 6 months

37 Participants Needed

Trial Summary

What is the purpose of this trial?

Status - CLOSED TO PATIENT ENROLLMENT (CNPE) Patients who have pancreatic cancer that has come back or has not gone away after treatment, including the standard treatment for this disease or patients who are not eligible for or have elected not to receive standard of care chemotherapy, and patients who will have surgery after treatment for pancreatic cancer are eligible for this study. This is a research study using special immune system cells called tumor-associated antigen (TAA)-specific cytotoxic T lymphocytes, a new experimental therapy. The proteins that are targeted in this study are called tumor-associated antigens (TAAs). These are cell proteins that are specific to the cancer cell. They do not show, or they show up in low quantities, on normal human cells. In this study, five common TAAs will be targeted. They are called NY-ESO-1, MAGEA4, PRAME, Survivin and SSX2. On a different study, patients have been treated and so far this treatment has shown to be safe. Investigators now want to try this treatment in patients with pancreatic cancer. These TAA-specific cytotoxic T lymphocytes (TAA-CTLs) are an investigational product not approved by the Food and Drug Administration. \*Arm A and Arm B are closed to new patient enrollment.\*

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you need to be off other investigational therapies for one month and conventional therapies for at least one week before starting the study treatment. If you are on systemic corticosteroids, you must stop them at least 48 hours before participating.

What data supports the effectiveness of the treatment multiTAA specific T cells for pancreatic cancer?

Research suggests that multiantigen-specific T-cell therapy, which uses a patient's own T cells to target cancer, shows promise in treating pancreatic cancer. In a phase I trial, this therapy was safe and showed positive responses in some patients with advanced disease when combined with chemotherapy. ^{1 2 3 4 5}

Is multiTAA specific T cell therapy safe for humans?

In a phase I trial, multiTAA specific T cell therapy was found to be safe for patients with advanced pancreatic cancer who were also receiving chemotherapy. ^{1 2 4 6 7}

How is the multiTAA specific T cells treatment different from other treatments for pancreatic cancer?

The multiTAA specific T cells treatment is unique because it uses the patient's own T cells, which are cultured with peptides from cancer-associated antigens to specifically target pancreatic cancer cells. This personalized immunotherapy approach is different from conventional treatments like chemotherapy, as it aims to harness the body's immune system to fight the cancer. ^{1 4 6 8 9}

Research Team

Benjamin Musher

Principal Investigator

Baylor College of Medicine

Anne Leen, PhD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for adults over 18 with pancreatic cancer that's persistent after treatment, or those who've chosen not to undergo standard chemotherapy. Candidates must have a life expectancy of at least 6 months, be off other investigational therapies for a month, and not be pregnant. Men must use condoms; women should use effective birth control if they can bear children.

Inclusion Criteria

You have a disease that can be measured or evaluated using specific criteria.

Patients with life expectancy greater than or equal to 12 weeks

I have been diagnosed with pancreatic cancer through a biopsy.

Exclusion Criteria

Pregnant

I am living with HIV.

You have HIV.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

T Cell Manufacturing

Blood is collected from patients to manufacture TAA-specific cytotoxic T cells in the lab, which takes about 1 to 2 months.

4-8 weeks

Treatment

Patients receive up to six doses of TAA-CTLs at monthly intervals, with pre-treatment using acetaminophen and diphenhydramine to prevent allergic reactions.

6 months

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with blood tests and imaging studies to evaluate tumor response.

12 months

Regular visits for blood tests and imaging

Long-term Follow-up

Investigators contact patients once a year for up to 4 additional years to evaluate disease response long-term.

4 years

Treatment Details

Interventions

• multiTAA specific T cells

Trial Overview The study tests TAA-specific cytotoxic T lymphocytes (TAA-CTLs), an experimental therapy targeting proteins unique to cancer cells in patients with pancreatic cancer. These immune cells are designed to attack five specific tumor-associated antigens (TAAs) that are present on the cancer but not normal cells.

Participant Groups

Group I: Group C (Closed to New Patient Enrollment) Experimental Treatment 1 Intervention

Patients with resectable pancreatic adenocarcinoma following completion of neoadjuvant chemotherapy, radiotherapy or combination. These patients will receive 6 infusions with a fixed dose of multiTAA specific T cells. One infusion will occur 4 weeks prior to surgical resection (with an option to infuse up to one week earlier) and after the completion of all pre-operative chemotherapy and/or radiation. The subsequent 5 infusions will occur at monthly intervals beginning 8 weeks post-surgery. Following surgery all patients will additionally receive 3 months of standard of care (SOC) chemotherapy starting week 9 after surgery. Hence, SOC chemo will occur weeks 9-11, 13-15, and 17-19 post-surgery and multiTAA T cell infusions will occur at weeks 8, 12, 16, 20, and 24 post-surgery.

Group II: Group B (Closed to New Patient Enrollment) Experimental Treatment 1 Intervention

Patients with locally advanced or metastatic pancreatic adenocarcinoma who have failed first line chemotherapy or are intolerant or ineligible to receive standard of care chemotherapy will be evaluated in the clinic and receive 6 infusions (administered at monthly intervals) with a fixed dose of multiTAA specific T cells.

Group III: Group A (Closed to New Patient Enrollment) Experimental Treatment 1 Intervention

Patients with locally advanced or metastatic pancreatic adenocarcinoma who are responding following 3 cycles of first line chemotherapy will receive 6 infusions with a fixed dose of multiTAA specific T cells beginning on the 4th week of the 4th cycle of chemotherapy. MultiTAA T cell infusions will occur on day 21 (a chemotherapy "off" week) of each chemotherapy cycle starting on chemotherapy cycle 4.

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Pancreatic Cancer Action Network

Collaborator

Trials

6

Recruited

10,000+

The V Foundation for Cancer Research

Collaborator

Trials

21

Recruited

1,300+

Harris County Hospital District

Collaborator

Trials

7

Recruited

410+

Findings from Research

A phase I trial of a multiantigen-specific T-cell therapy using patients' own nonengineered T cells showed safety and potential effectiveness in treating advanced pancreatic cancer.

Patients receiving this therapy, alongside chemotherapy, exhibited responses, suggesting that this approach could enhance treatment outcomes for those with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy Shows Promise in Pancreatic Cancer. [2020]

Autologous cytotoxic T lymphocytes (CTLs) specific for the CEA691 peptide can be successfully generated from pancreatic cancer patients, showing the potential for targeted immunotherapy against this cancer.

Blocking PD-L1 ex vivo significantly enhances the function of these CEA691-specific CTLs, particularly those isolated from tumor-draining lymph nodes, suggesting a promising strategy to improve anti-tumor responses in pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ex Vivo PD-L1/PD-1 Pathway Blockade Reverses Dysfunction of Circulating CEA-Specific T Cells in Pancreatic Cancer Patients. Chen, Y., Xue, SA., Behboudi, S., et al.[2023]

References

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

Immunotherapy Shows Promise in Pancreatic Cancer. [2020]

2. England pubmed.ncbi.nlm.nih.gov

T cell optimization for the treatment of pancreatic cancer. [2018]

3. China pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor (CAR) T and other T cell strategies for pancreas adenocarcinoma. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Engineered T cells for pancreatic cancer treatment. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Effect of adoptive T-cell immunotherapy on immunological parameters and prognosis in patients with advanced pancreatic cancer. [2021]

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

Human pancreatic cancer cells (MPanc-96) recognized by autologous tumor-infiltrating lymphocytes after in vitro as well as in vivo tumor expansion. [2019]

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

Novel bispecific antibodies increase γδ T-cell cytotoxicity against pancreatic cancer cells. [2021]

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

Ex Vivo PD-L1/PD-1 Pathway Blockade Reverses Dysfunction of Circulating CEA-Specific T Cells in Pancreatic Cancer Patients. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Identification of HLA-A2-restricted CTL epitopes of a novel tumour-associated antigen, KIF20A, overexpressed in pancreatic cancer. [2022]