Afamitresgene Autoleucel for Sarcoma

Not currently recruiting at 27 trial locations

Overseen By Adaptimmune Patient Enquiries

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Adaptimmune

Must not be taking: Cytotoxic chemotherapy, TKIs

Disqualifiers: Autoimmune disease, CNS metastases, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called afamitresgene autoleucel, a type of T-cell therapy, for individuals with synovial sarcoma or myxoid liposarcoma. These are types of soft tissue cancer that have spread or cannot be operated on. The trial aims to evaluate the treatment's effectiveness and safety. It targets individuals with specific tumor markers who have previously tried other cancer treatments, such as anthracyclines or ifosfamide. Participants must have a specific genetic marker (HLA-A*02), and their tumors must express a certain protein (MAGE-A4). This trial may suit those meeting these criteria and seeking new treatment options. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that afamitresgene autoleucel, or afami-cel, has been tested in individuals with advanced synovial sarcoma, a type of cancer. Studies have found that this treatment is generally well-tolerated. Specifically, one study revealed that 44% of patients with late-stage synovial sarcoma responded positively after just one dose of afami-cel, indicating potential effectiveness for some patients.

While the treatment appears promising, awareness of possible side effects is crucial. Some participants in earlier studies experienced mild to moderate side effects, though serious issues were less common. As this treatment remains under investigation, anyone considering joining a trial should discuss potential risks and benefits with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sarcoma?

Researchers are excited about afamitresgene autoleucel because it offers a new approach to treating sarcoma by using genetically modified T cells. Unlike traditional treatments like surgery, chemotherapy, or radiation, which directly target the tumor, this therapy modifies a patient's own immune cells to recognize and attack cancer cells specifically. This personalized approach can potentially lead to more effective targeting of the cancer with fewer side effects. The use of SPEAR™ T cells in afamitresgene autoleucel represents a cutting-edge advancement in immunotherapy, aiming to empower the body's own defenses to fight sarcoma more efficiently.

What evidence suggests that afamitresgene autoleucel could be an effective treatment for synovial sarcoma?

Research has shown that afamitresgene autoleucel, or afami-cel, could be promising for treating advanced synovial sarcoma. This treatment uses a patient's own T cells, modified to target a specific cancer marker called MAGE-A4. Studies have found that patients with synovial sarcoma who received afami-cel had encouraging survival rates, particularly those who responded well to the treatment. The therapy demonstrated lasting effects, indicating its potential effectiveness. Overall, evidence suggests afami-cel could be a helpful option for those with advanced synovial sarcoma. ^{1 2 3 4 6}

Who Is on the Research Team?

Dejka Araujo, MD

Principal Investigator

MD Anderson Cancer Center; Houston TX 77030

Are You a Good Fit for This Trial?

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.

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

I do not have any unmanaged ongoing illnesses.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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]

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]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT04044768

Spearhead 1 Study in Subjects With Advanced Synovial ... 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 ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.11563

The SPEARHEAD-1 trial of afamitresgene autoleucel ... Pts with advanced synovial sarcoma treated with afami-cel in SPEARHEAD-1 had encouraging survival, especially those pts with a RECIST response.

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

Adoptive T Cell Therapy Targeting MAGE-A4 - PMC One promising new treatment is called MAGE A4-targeted autologous T cell genetic therapy. “Autologous” means the therapy uses the patient's own cells.

5. targetedonc.com targetedonc.com/view/spear-t-cell-therapy-induces-durable-responses-in-synovial-sarcoma-and-myxoid-round-cell-liposarcoma

SPEAR T-Cell Therapy Induces Durable Responses in ... Afamitresgene autoleucel (Afami-cel) formerly ADP-A2M4) has demonstrated efficacy and an encouraging durability of responses in patients with advanced synovial ...

6. adaptimmune.com adaptimmune.com/investors-and-media/news-center/press-releases/detail/238/publication-of-data-from-adaptimmunes-completed-phase-1

Press Releases The response rate was 44% in patients with late-stage, metastatic synovial sarcoma after a single dose of afami-cel.