Afamitresgene Autoleucel for Sarcoma

Recruiting at 25 trial locations

Overseen By Adaptimmune Patient Enquiries

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Adaptimmune

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 6

Duration: 24 weeks

52 Participants Needed

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those who have received certain treatments like cytotoxic chemotherapy, tyrosine kinase inhibitors, and immune therapies before joining. It's best to discuss your specific 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 data supports the effectiveness of the treatment afamitresgene autoleucel for sarcoma?

Research shows that afamitresgene autoleucel, a treatment using engineered T-cells to target a specific cancer protein, shrank tumors in various cancers, with the best results in synovial sarcoma, achieving a disease control rate of about 90% and a partial response rate of 44% in a small trial. ^{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 afamitresgene autoleucel safe for humans?

In a phase 1 trial, afamitresgene autoleucel showed a manageable safety profile, with all patients experiencing some blood-related side effects and over half experiencing cytokine release syndrome (a condition where the immune system releases too many proteins into the blood too quickly). Despite these side effects, the treatment was considered to have an acceptable balance of benefits and risks, especially for synovial sarcoma patients. ^{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}

How is the treatment afamitresgene autoleucel unique for sarcoma?

Afamitresgene autoleucel is a unique treatment for sarcoma because it uses genetically engineered T-cells to specifically target and attack cancer cells expressing the MAGE-A4 antigen, which is not a standard approach for sarcoma. This therapy has shown promising results, especially in synovial sarcoma, with a high disease control rate and manageable side effects. ^{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.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive T-cell infusion and are monitored for response and adverse events

24 weeks

Visits at Week 4, Week 8, Week 12, Week 16, and Week 24

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2.6 years

Every 2 months until confirmed disease progression

Long-term follow-up

Participants are monitored for long-term safety and survival outcomes

Up to 3.2 years

Treatment Details

Interventions

• afamitresgene autoleucel

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

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

Approved in United States as Tecelra for:

• Unresectable or metastatic synovial sarcoma in adults who have received prior chemotherapy, are HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive and whose tumor expresses the MAGE-A4 antigen as determined by FDA-approved or cleared companion diagnostic devices.

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]