Afamitresgene Autoleucel for Pediatric Cancer

Recruiting in Palo Alto (17 mi)

+12 other locations

Overseen by Fiorella Iglesias Cardenas

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Adaptimmune

Must not be taking: Fludarabine, Cyclophosphamide

Disqualifiers: Autoimmune disease, CNS metastases, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This is a pediatric basket study to investigate the safety and efficacy of afamitresgene autoleucel in HLA-A\*02 eligible and MAGE-A4 positive subjects aged 2-21 years of age with advanced cancers

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the treatment Afamitresgene autoleucel for pediatric cancer?

In a phase 1 trial, Afamitresgene autoleucel (afami-cel) showed promise in shrinking tumors, especially in synovial sarcoma, with a disease control rate of around 90% and a partial response rate of 44% in synovial sarcoma patients. The treatment was found to infiltrate tumors and trigger immune responses, indicating its potential effectiveness. ^{1 2 3 4 5}

Is Afamitresgene Autoleucel safe for use in humans?

In a phase 1 trial, Afamitresgene Autoleucel (afami-cel) was tested in patients with various solid tumors, and all participants experienced some level of blood-related side effects, with 55% experiencing a manageable condition called cytokine release syndrome. The treatment showed an acceptable balance between benefits and risks, suggesting it is generally safe for further testing. ^{1 3 4 5 6}

What makes the treatment Afamitresgene Autoleucel unique for pediatric cancer?

Afamitresgene Autoleucel is a unique treatment because it uses genetically engineered T-cells to specifically target and attack cancer cells expressing the MAGE-A4 antigen, which is found in various solid tumors. This personalized approach enhances the immune system's ability to fight cancer, offering a novel option especially for conditions like synovial sarcoma where traditional treatments may be limited. ^{1 2 3 4 5}

Research Team

Fiorella Iglesias Cardenas

Principal Investigator

Memorial Sloan Kettering Kids

Eligibility Criteria

This trial is for children and young adults aged 2-21 with certain advanced cancers like Osteosarcoma or Neuroblastoma. They must have had chemotherapy before, weigh at least 10 kg, and their cancer should be measurable by medical scans. Participants need to have a specific immune system marker (HLA-A*02) and a protein on their tumor cells (MAGE-A4).

Inclusion Criteria

I am between 2 and 21 years old.

I weigh at least 10 kilograms.

I have undergone chemotherapy before.

Exclusion Criteria

Pregnant or breastfeeding

History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide

My cancer has spread to my brain.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive afamitresgene autoleucel to assess safety, tolerability, and anti-tumor activity

3.5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

3.5 years

Long-term Follow-up

Participants are monitored for overall survival and long-term safety

15 years

Treatment Details

Interventions

• Afamitresgene autoleucel (CAR T-cell Therapy)

Trial Overview The study tests afamitresgene autoleucel's safety and effectiveness in treating pediatric patients with advanced cancers that express MAGE-A4. It's for those who are HLA-A*02 positive, focusing on how well they respond to this therapy.

Participant Groups

Group I: Afamitresgene autoleucel Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Adaptimmune

Lead Sponsor

Trials

25

Recruited

10,000+

Findings from Research

ADP-A2M10, a genetically engineered T-cell therapy targeting MAGE-A10-positive tumors, demonstrated an acceptable safety profile with no off-target toxicity in a phase 1 trial involving 10 patients with advanced cancers.

The therapy showed persistence in the bloodstream and the ability to infiltrate tumors, particularly in higher dose groups, although the best clinical responses were stable disease in four patients and progressive disease in five.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 Clinical Trial Evaluating the Safety and Anti-Tumor Activity of ADP-A2M10 SPEAR T-Cells in Patients With MAGE-A10+ Head and Neck, Melanoma, or Urothelial Tumors. Hong, DS., Butler, MO., Pachynski, RK., et al.[2022]

The study identified a specific peptide (MAGE-A4 280-299) that can effectively stimulate the growth of MAGE-A4-specific Th1 cells, which are crucial for inducing anti-tumor immunity.

Using this peptide, researchers developed a method to expand these Th1 cells in vitro, showing that they produce important immune signals (IFN-gamma and IL-2) that could enhance the effectiveness of adoptive immunotherapy for cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of novel helper epitopes of MAGE-A4 tumour antigen: useful tool for the propagation of Th1 cells. Ohkuri, T., Wakita, D., Chamoto, K., et al.[2021]

ADP-A2M10, a genetically engineered T cell therapy targeting MAGE-A10 in advanced non-small cell lung cancer (NSCLC), showed an acceptable safety profile with no off-target toxicity, although some patients experienced significant adverse events like lymphopenia and cytokine release syndrome.

The therapy demonstrated persistence in the bloodstream and tumor tissue, with higher doses leading to better persistence, indicating potential for effective antitumor activity, although only one patient achieved a partial response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical trial evaluating the safety and efficacy of ADP-A2M10 SPEAR T cells in patients with MAGE-A10+ advanced non-small cell lung cancer. Blumenschein, GR., Devarakonda, S., Johnson, M., et al.[2022]

Afamitresgene autoleucel (afami-cel) is a promising T cell therapy targeting MAGE-A4 in patients with relapsed/refractory metastatic solid tumors, showing a 24% overall response rate, particularly effective in synovial sarcoma with a 44% response rate.

The therapy demonstrated an acceptable safety profile, with all patients experiencing Grade ≥3 hematologic toxicities and 55% experiencing cytokine release syndrome, but it also showed early and durable responses, with a median duration of response of 25.6 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous T cell therapy for MAGE-A4+ solid cancers in HLA-A*02+ patients: a phase 1 trial. Hong, DS., Van Tine, BA., Biswas, S., et al.[2023]

In a phase I trial, autologous T cells engineered to target the MAGE-A4 cancer testis antigen (ADP-A2M4) demonstrated significant efficacy, particularly in synovial sarcoma, achieving a disease control rate of approximately 90%.

The therapy was associated with a manageable toxicity profile, indicating that it is a potentially safe treatment option for patients with a variety of solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T Cells Targeting MAGE-A4 Shrink Tumors. [2021]

The peptide EADPTGHSY, encoded by the MAGE-A1 gene, is effective in targeting tumor cells in patients with HLA-B35, expanding its potential use in cancer immunotherapy.

A cytotoxic T-lymphocyte clone was able to recognize and kill tumor cells expressing MAGE-A1 when presented by HLA-B35, indicating that this treatment could benefit approximately 19% of Caucasian patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A MAGE-A1 peptide presented to cytolytic T lymphocytes by both HLA-B35 and HLA-A1 molecules. Luiten, RM., Demotte, N., Tine, J., et al.[2019]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Phase 1 Clinical Trial Evaluating the Safety and Anti-Tumor Activity of ADP-A2M10 SPEAR T-Cells in Patients With MAGE-A10+ Head and Neck, Melanoma, or Urothelial Tumors. [2022]

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

Identification of novel helper epitopes of MAGE-A4 tumour antigen: useful tool for the propagation of Th1 cells. [2021]

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

Phase I clinical trial evaluating the safety and efficacy of ADP-A2M10 SPEAR T cells in patients with MAGE-A10+ advanced non-small cell lung cancer. [2022]

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

Autologous T cell therapy for MAGE-A4+ solid cancers in HLA-A*02+ patients: a phase 1 trial. [2023]

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

T Cells Targeting MAGE-A4 Shrink Tumors. [2021]

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

A MAGE-A1 peptide presented to cytolytic T lymphocytes by both HLA-B35 and HLA-A1 molecules. [2019]