Afamitresgene Autoleucel for Sarcoma

Recruiting at25 trial locations

Overseen by Dejka Araujo, MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Adaptimmune

No Placebo Group

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This is a study to investigate the efficacy and safety of ADP-A2M4 in HLA-A\*02 eligible and MAGE-A4 positive subjects with metastatic or inoperable (advanced) Synovial Sarcoma (Cohort 1, 2 and 3 ) or MRCLS (Cohort 1) .

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have received certain treatments like cytotoxic chemotherapy, tyrosine kinase inhibitors, immune therapy, or corticosteroids before participating. It's best to discuss your current medications with the trial team.

What data supports the idea that Afamitresgene Autoleucel for Sarcoma is an effective treatment?

The available research shows that Afamitresgene Autoleucel, also known as ADP-A2M4, is effective in treating synovial sarcoma, a type of cancer. In a phase 1 trial, 44% of patients with synovial sarcoma showed a positive response to the treatment, meaning their tumors shrank. Additionally, the treatment had a disease control rate of around 90% for synovial sarcoma, indicating that it was able to stop the cancer from getting worse in most patients. These results suggest that Afamitresgene Autoleucel is a promising treatment for this type of cancer. ^{1 2 3 4 5}

What safety data is available for Afamitresgene Autoleucel treatment in sarcoma?

Afamitresgene autoleucel (afami-cel) has been evaluated in a phase 1 trial for safety in patients with MAGE-A4+ solid tumors, including synovial sarcoma. All patients experienced Grade ≥3 hematologic toxicities, and 55% experienced cytokine release syndrome, mostly Grade ≤2. The treatment showed an acceptable benefit-risk profile, with early and durable responses, especially in metastatic synovial sarcoma. The trial's small size limits conclusions, but results support further testing. ^{1 2 3 4 6}

Is the treatment afamitresgene autoleucel a promising treatment for sarcoma?

Yes, afamitresgene autoleucel is a promising treatment for sarcoma, especially synovial sarcoma. It has shown early and lasting responses in patients, with a disease control rate of around 90% in synovial sarcoma cases. ^{1 2 3 4 7}

Research Team

Dejka Araujo, MD

Principal Investigator

MD Anderson Cancer Center; Houston TX 77030

Eligibility Criteria

This trial is for people aged 16-75 with advanced synovial sarcoma or myxoid/round cell liposarcoma, who've had certain chemotherapies. They must have measurable disease, be HLA-A*02 positive without the HLA-A*02:05 allele, and show MAGE-A4 expression. Exclusions include autoimmune diseases, other active cancers, significant heart disease, uncontrolled illnesses, infections like HIV or hepatitis B/C, pregnancy/breastfeeding and allergies to study drugs.

Inclusion Criteria

I am between 16 and 75 years old, or between 10 and 75 at certain locations.

I have been treated with anthracycline or ifosfamide before.

I am HLA-A*02 positive.

Exclusion Criteria

I have brain metastases causing symptoms.

I do not have any unmanaged ongoing illnesses.

You have a history of a disease where your immune system attacks your own body.

Treatment Details

Interventions

• afamitresgene autoleucel (CAR T-cell Therapy)

Trial Overview The Spearhead 1 Study tests afamitresgene autoleucel (ADP-A2M4) in patients with metastatic or inoperable Synovial Sarcoma or Myxoid/Round Cell Liposarcoma. It's focused on those eligible for HLA-A*02 and positive for MAGE-A4 protein to assess the treatment's effectiveness and safety.

Participant Groups

Group I: Autologous genetically modified afamitresgene autoleucel (previously ADP-A2M4) SPEAR™ T cells Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Adaptimmune

Lead Sponsor

Trials

25

Recruited

10,000+

Findings from Research

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]

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]

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]

The study developed an affinity-enhanced T cell receptor (TCR) targeting the MAGE A3 antigen for cancer therapy, which showed promising preclinical results with no off-target effects; however, it led to a serious adverse event in patients, indicating potential safety risks.

Post-adverse event investigations revealed that the TCR also recognized a peptide from the muscle protein Titin, suggesting that off-target recognition can occur in vivo, emphasizing the need for improved preclinical testing methods to prevent such toxicities in future therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of a Titin-derived HLA-A1-presented peptide as a cross-reactive target for engineered MAGE A3-directed T cells. Cameron, BJ., Gerry, AB., Dukes, J., et al.[2023]

The study identified specific T cell epitopes from the MAGE-A3 antigen that can effectively activate and kill cancer cells in patients with advanced non-small cell lung cancer (NSCLC), particularly focusing on the Mp4 epitope.

T cells engineered to express TCRs specific to the MAGE-A3-Mp4 epitope showed strong recognition and killing of MAGE-A3+ tumor cells, with a low risk of cross-reactivity, suggesting a promising approach for targeted immunotherapy in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Global analysis of HLA-A2 restricted MAGE-A3 tumor antigen epitopes and corresponding TCRs in non-small cell lung cancer. Zhang, B., Ren, Z., Zhao, J., et al.[2023]

References

1. 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]

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

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

5. 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]

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

Identification of a Titin-derived HLA-A1-presented peptide as a cross-reactive target for engineered MAGE A3-directed T cells. [2023]

7. Australia pubmed.ncbi.nlm.nih.gov

Global analysis of HLA-A2 restricted MAGE-A3 tumor antigen epitopes and corresponding TCRs in non-small cell lung cancer. [2023]