Afamitresgene autoleucel in advanced synovial sarcoma and myxoid round cell liposarcoma

A new phase 2 trial recently published on The Lancet shows that afamitresgene autoleucel (afami-cel) can induce durable responses with an acceptable benefit-to-risk profile in heavily pretreated HLA-eligible patients with MAGE-A4-expressing advanced synovial sarcoma.

T-cell receptor therapies have led to important advances in the treatment of certain subsets of B-cell leukaemia and lymphoma, but none has been approved for the treatment of any solid tumor. Affinity-optimised engineered T-cell receptors have emerged as a promising tool for application of autologous T cells to treat solid tumors. MAGE-A4, a cancer testis antigen, is expressed in germline tissue and various solid tumors, including synovial sarcoma and myxoid round cell liposarcoma, and is a promising target for cancer immunotherapy. Afami-cel is an autologous T-cell receptor T-cell therapy engineered to express an affinity-enhanced T-cell receptor specifically targeting a MAGE-A4 antigen; in a phase 1 trial afami-cel has been evaluated in patients with relapsing or refractory solid tumors expressing MAGE-4, ranging from synovial sarcoma to head and neck cancers.  An acceptable benefit-to-risk profile and durable responses were observed especially in patients with synovial sarcoma, therefore this phase 2 trial involved 52 heavily pretreated patients followed-up for a median of 32.6 months. Overall response rate was 37% overall, 39% for patients with synovial sarcoma, and 25% for patients with myxoid round cell liposarcoma, with cytopenias as the most common grade 3 or worse adverse events. As authors conclude, «This study shows the ability to effectively target solid tumor cancer antigens with T-cell receptor therapy and highlights MAGE-A4 as a new immunotherapy target for treatment of synovial sarcoma».