MAGE-A4ᶜ¹º³²T Therapy for Cancer

Recruiting at 10 trial locations

Overseen By David Hong, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Adaptimmune

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

Compensation: Varies

Number of Visits: Unknown

Duration: 3.5 years

71 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will investigate the safety and tolerability of MAGE-A4ᶜ¹º³²T cell therapy in subjects who have the appropriate HLA-A2 tissue marker and whose urinary bladder, melanoma, head and neck, ovarian, non-small cell lung, esophageal, gastric, synovial sarcoma, or myxoid/round call liposarcoma (MRCLS) tumor has the MAGE-A4 protein expressed. This study will take a subject's T cells and give them a T cell receptor protein that recognizes and attacks the tumors. This study has a substudy component that will investigate the safety and tolerability of MAGE-A4c1032T cell therapy in combination with low dose radiation in up to 10 subjects.

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 subjects receiving excluded therapy or treatment per protocol are not eligible, which might imply some medications could be restricted. It's best to discuss your specific medications with the trial coordinators.

What data supports the effectiveness of the MAGE-A4ᶜ¹º³²T treatment for cancer?

Research shows that MAGE-A4, a protein found in some cancer cells, can be a target for immunotherapy, which uses the body's immune system to fight cancer. This protein is present in various cancers, making it a promising target for treatments that aim to boost the immune response against tumors. ^{1 2 3 4 5}

How is the MAGE-A4ᶜ¹º³²T treatment different from other cancer treatments?

MAGE-A4ᶜ¹º³²T therapy is unique because it is a type of immunotherapy that uses the body's own immune system to target cancer cells by recognizing specific antigens (proteins) on the tumor, which is different from traditional chemotherapy that attacks all rapidly dividing cells. ^{6 7 8 9 10}

Research Team

David Hong, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults aged 18-75 with certain cancers (like sarcoma, melanoma, and lung cancer) that express the MAGE-A4 protein and are HLA-A*02 positive. They should have measurable disease, adequate organ function, a life expectancy over 6 months, and no active infections like HIV or hepatitis.

Inclusion Criteria

You are expected to live for at least 6 months before a certain procedure and 3 months before another procedure.

My tumor tests positive for MAGE-A4.

I am HLA-A*02 positive.

Exclusion Criteria

Subject is pregnant or breastfeeding.

I have no other active cancers and no uncontrolled illnesses.

I have symptoms from cancer spreading to my brain.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MAGE-A4ᶜ¹º³²T cell therapy, potentially in combination with low dose radiation

3.5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 years

Treatment Details

Interventions

• Autologous genetically modified MAGE-A4c1032T cells combined with low dose radiation
• MAGE-A4ᶜ¹º³²T

Trial Overview The study tests MAGE-A4ᶜ¹º³²T cell therapy where patients' T cells are modified to attack tumors expressing MAGE-A4. A subgroup will also receive these T cells plus low-dose radiation to assess safety and effectiveness of this combination.

Participant Groups

Group I: Radiation Sub-Study: Autologous genetically modified MAGE-A4c1 Experimental Treatment 1 Intervention

Group II: Autologous genetically modified MAGE-A4ᶜ¹º³²T cells Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Adaptimmune

Lead Sponsor

Trials

25

Recruited

10,000+

Findings from Research

In a phase II study involving 44 patients with gemcitabine-refractory pancreatic cancer, FOLFOX4 demonstrated an objective response rate of 11.4% and a tumor stabilization rate of 40.9%, indicating its potential efficacy as a rescue therapy.

FOLFOX4 was generally well-tolerated, but significant hematologic toxicities were observed, including grade 3 or 4 neutropenia in 43.2% of patients, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Folfox4 as a rescue chemotherapy for gemcitabine-refractory pancreatic cancer. Chung, JW., Jang, HW., Chung, MJ., et al.[2022]

Immunotherapy shows promise in treating pancreatic cancer by activating T cells to target tumor-specific antigens, which is crucial since conventional therapies have limited effectiveness.

Preclinical studies suggest that combining immunotherapy with chemotherapy or targeted therapy may enhance treatment outcomes, leading to ongoing trials focused on finding effective and less toxic treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy for pancreatic cancer. Kotteas, E., Saif, MW., Syrigos, K.[2023]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Impact of MAGE-A antigens on taxane response in oral squamous cell carcinoma. [2021]

2. Japan pubmed.ncbi.nlm.nih.gov

Clinical significance of human leukocyte antigen loss and melanoma-associated antigen 4 expression in smokers of non-small cell lung cancer patients. [2021]

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

Development of a CD8 co-receptor independent T-cell receptor specific for tumor-associated antigen MAGE-A4 for next generation T-cell-based immunotherapy. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

MAGE-A Antigens and Cancer Immunotherapy. [2020]

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

Serum MAGE-4 protein in ovarian cancer patients. [2006]

6. England pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy with MUC1-mRNA transfected dendritic cells and cytotoxic lymphocytes plus gemcitabine for unresectable pancreatic cancer. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel plus gemcitabine with or without capecitabine and cisplatin in metastatic pancreatic adenocarcinoma (PACT-19): a randomised phase 2 trial. [2022]

8. Greece pubmed.ncbi.nlm.nih.gov

Folfox4 as a rescue chemotherapy for gemcitabine-refractory pancreatic cancer. [2022]

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

Salvage chemotherapy with mitomycin, docetaxel, and irinotecan (MDI regimen) in metastatic pancreatic adenocarcinoma: a phase I and II trial. [2019]

10. Germany pubmed.ncbi.nlm.nih.gov

Immunotherapy for pancreatic cancer. [2023]