The US Food and Drug Administration approved Tecelra (afamitresgene autoleucel), a gene therapy indicated for the treatment of adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA antigen(s) A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive, and whose tumour expresses the MAGE-A4 antigen as determined by FDA authorised companion diagnostic devices.
Synovial sarcoma is a rare form of cancer in which malignant cells develop and form tumours in the soft tissues of the body. This type of cancer can occur in many parts of the body, most commonly developing in the extremities. The cancerous cells may also spread to other parts of the body. Each year, synovial sarcoma impacts about 1,000 people in the US and most often occurs in adult males in their 30s or younger. Treatment typically involves surgery to remove the tumour and may also include radiotherapy and/or chemotherapy if the tumour is larger, returns after being removed or has spread beyond its original location.
“Potentially life-threatening cancers such as synovial sarcoma continue to have a devastating impact on individuals, especially those for whom standard treatments have limited efficacy due to tumour growth and progression,” said Peter Marks, MD, PhD, Director, Center for Biologics Evaluation and Research (CBER), FDA.
Tecelra is also the first FDA-approved T cell receptor (TCR) gene therapy. The product is an autologous T cell immunotherapy composed of a patient’s T cells. T cells in Tecelra are modified to express a TCR that targets MAGE-A4, an antigen (a substance that normally triggers your immune system) expressed by cancer cells in synovial sarcoma. The product is administered as a single intravenous dose.
Tecelra was approved using the Accelerated Approval pathway, under which the FDA may approve drugs for serious or life-threatening diseases or conditions where there is an unmet medical need and the drug is shown to affect a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients (improving how patients feel or function, or whether they survive longer). This pathway can allow earlier approval while the company conducts further trials to verify the predicted clinical benefit. A confirmatory trial is ongoing to verify Tecelra’s clinical benefit.
“Adults with metastatic synovial sarcoma, a life-threatening form of cancer, often face limited treatment options in addition to the risk of cancer spread or recurrence,” said Nicole Verdun, M.D., Director, Office of Therapeutic Products, CBER.
The safety and effectiveness of Tecelra were evaluated in a multicentre, open-label clinical trial including patients with inoperable and metastatic synovial sarcoma who had received prior systemic therapy and whose tumour expressed the MAGE-A4 tumour antigen. Effectiveness was evaluated based on the overall response rate and the duration of response to treatment with Tecelra. Among the 44 patients in the trial who received Tecelra, the overall response rate was 43.2 per cent and the median duration of response was six months.
The most common adverse reactions associated with Tecelra included nausea, vomiting, fatigue, infections, fever, constipation, dyspnea (shortness of breath), abdominal pain, non-cardiac chest pain, decreased appetite, tachycardia (abnormally fast heart rate), back pain, hypotension, diarrhoea and oedema (swelling due to buildup of fluid in body tissues).
Patients treated with Tecelra may experience cytokine release syndrome (CRS), which is a dangerous type of aggressive immune system response, including potentially life-threatening reactions. CRS was observed following the administration of Tecelra during clinical trials. A Boxed Warning is included in the label containing information about this risk.
Patients may also exhibit Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS), an immune system-related syndrome that can occur following some immunotherapies, infections, secondary malignancies, or hypersensitivity reactions, and severe cytopenia (an abnormally low level of blood cells) for several weeks following lymphodepleting chemotherapy and Tecelra infusion. Patients receiving this product should be monitored for signs and symptoms of infection and are advised not to drive or engage in hazardous occupations or activities for at least four weeks after receiving Tecelra.
The FDA granted Tecelra Orphan Drug, Regenerative Medicine Advanced Therapy and Priority Review designations for this indication. This application was reviewed using a coordinated, cross-agency approach, including CBER, the FDA’s Oncology Center of Excellence and the Center for Devices and Radiological Health. The FDA granted the approval of Tecelra to Adaptimmune.