Afamitresgene Autoleucel for Pediatric Cancer

Recruiting at 13 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Adaptimmune

Must not be taking: Fludarabine, Cyclophosphamide

Disqualifiers: Autoimmune disease, CNS metastases, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3.5 years

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment called afamitresgene autoleucel, a type of T-cell therapy, for children and teens with advanced cancers such as synovial sarcoma and neuroblastoma. It targets those whose cancers have not responded well to previous treatments. The trial seeks participants diagnosed with these cancers who have undergone chemotherapy and meet specific genetic criteria (HLA-A*02 positive and MAGE-A4 positive). This study offers a promising opportunity for eligible individuals to try a new therapy that could help manage their condition. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, giving participants the chance to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that afamitresgene autoleucel is likely to be safe for humans?

Research has shown that afamitresgene autoleucel, a treatment using a patient's own T cells to fight cancer, has been tested for safety in people with certain solid tumors. The FDA has already approved the treatment for some types of cancer, indicating it met safety standards for those cases. However, common side effects have been reported, including cytokine release syndrome (a reaction that can cause fever and tiredness), nausea, vomiting, fatigue, infections, and fever. In earlier studies, these side effects occurred in at least 20% of patients. It is crucial to discuss with doctors how these side effects might affect young patients in this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Afamitresgene autoleucel is unique because it harnesses the power of genetically modified T cells to specifically target and attack cancer cells in pediatric patients. Unlike traditional chemotherapy and radiation, which can harm healthy cells and come with harsh side effects, this treatment uses a patient's own immune cells that are engineered to recognize and destroy cancer cells. Researchers are excited about this innovative approach because it represents a more personalized and potentially less toxic therapy, which could lead to better outcomes and improved quality of life for young patients battling cancer.

What evidence suggests that afamitresgene autoleucel might be an effective treatment for pediatric cancer?

Research has shown that afamitresgene autoleucel, the treatment under study in this trial, is a promising therapy for some advanced cancers. This therapy uses a patient's own immune cells to fight cancer and specifically targets a protein called MAGE-A4 found on certain cancer cells. Previous studies demonstrated that this treatment works well against tumors with MAGE-A4. The FDA granted it accelerated approval for use in adults with specific cancers, such as synovial sarcoma, after chemotherapy. This suggests it could also effectively treat advanced cancers in children. ^{1 2 3 4 5}

Who Is on the Research Team?

Fiorella Iglesias Cardenas

Principal Investigator

Memorial Sloan Kettering Kids

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Afamitresgene autoleucel

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.

How Is the Trial Designed?

Group I: Afamitresgene autoleucel Experimental Treatment 1 Intervention

Afamitresgene autoleucel is already approved in United States for the following indications:

Approved in United States as TECELRA for:

• Unresectable or metastatic synovial sarcoma

Who Is Running the Clinical Trial?

Adaptimmune

Lead Sponsor

Trials

25

Recruited

10,000+

Published Research Related to This Trial

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-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]

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]

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]

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]

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]

Citations

1. nature.com nature.com/articles/s41591-022-02128-z

Autologous T cell therapy for MAGE-A4 + solid cancers in ... Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11815873/

Adoptive T Cell Therapy Targeting MAGE-A4 - PMC Though the ADP A2M4 TCR demonstrated excellent effectiveness against certain MAGE A4-associated tumors in recent trials, further advances in the development of ...

3. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-afamitresgene-autoleucel-unresectable-or-metastatic-synovial-sarcoma

FDA grants accelerated approval to afamitresgene ... The most common grade 3 or 4 laboratory abnormalities (≥ 20%) were lymphocyte count decreased, neutrophil count decreased, white cell blood ...

4. cancer.gov cancer.gov/news-events/cancer-currents-blog/2024/fda-tecelra-synovial-sarcoma-mage-a4

First Cancer TCR Cell Therapy Approved by FDA - NCI Afami-cel is approved for patients who have been treated with chemotherapy and whose tumors test positive for the presence of MAGE-A4 and ...

5. mskcc.org mskcc.org/cancer-care/clinical-trials/23-244

A Phase 1/2 Study of Afamitresgene Autoleucel SPEAR T ... Researchers are assessing a new type of therapy in young people with solid tumors that keep growing even after treatment. The therapy is called afamitresgene ...