Groundbreaking cell therapy pending FDA approval
TCR-T for Synovial Sarcoma reaching curative effects
In a significant development, Adaptimmune Therapeutics (NASDAQ: ADAP) ( https://www.adaptimmune.com/pipeline) , a pioneering company specializing in tumor cell therapy, has commenced the rolling Biologics License Application (BLA) process with the U.S. Food and Drug Administration (FDA) for its groundbreaking TCR-T cell therapy, afami-cel. The therapy holds promise for treating advanced synovial sarcoma, a challenging form of cancer. If successful, afami-cel would mark a historic milestone as the first-ever TCR-T cell therapy approved for solid tumors.
Synovial sarcoma, a rare and aggressive malignant tumor originating from mesenchymal cells, primarily affects soft tissues surrounding joints, synovium, and tendon sheaths. Comprising 8% to 10% of all soft tissue sarcomas, this formidable disease is most prevalent among adolescents and young adults under 30, with an incidence rate of approximately 2.75 cases per million individuals. With a notoriously poor prognosis, synovial sarcoma poses a significant treatment challenge. While chemotherapy stands as the current first-line option, its efficacy remains limited. Other alternatives such as antibodies and inhibitors have yielded even more constrained results.
This cell therapy, afami-cel's innovative approach revolves around targeting the MAGE-A4 antigen through TCR-T cell therapy. MAGE-A4, a cancer-testis antigen and crucial member of the melanoma-associated antigen-A (MAGE-A) subfamily, exhibits a remarkable degree of histological specificity.
Reaching curative effects
At the recently held Connective Tissue Oncology Society (CTOS) Annual Meeting, Adaptimmune unveiled the final analysis data from Cohort 1 of its groundbreaking SPEARHEAD-1 trial, evaluating the effectiveness of afami-cel in treating advanced synovial sarcoma and myxoid/round cell liposarcoma patients.
As of August 29, 2022, 52 patients (44 with synovial sarcoma and 8 with myxoid/round cell liposarcoma) received afami-cel treatment in the trial, with a median age of 41 years (ranging from 19 to 73 years). Among these patients, who had undergone initial systemic therapy, the overall response rate (ORR) stood at an encouraging 36.5% (38.6% for synovial sarcoma and 25.0% for myxoid/round cell liposarcoma), while the disease control rate reached an impressive 88.4%. Notably, synovial sarcoma patients experienced a median duration of response of 50.3 weeks!
afami-cel exhibited a favorable safety profile, with manageable adverse events primarily characterized by low-grade cytokine release syndrome and tolerable/reversible hematological toxicities. Pioneering translational research in immunotherapy has highlighted afami-cel's ability to effectively activate and foster the infiltration of proliferative cytotoxic T cells into tumors, potentially bolstering its potent anti-tumor response.
With Cohort 1 of the SPEARHEAD-1 trial successfully completing treatment and achieving primary efficacy endpoints, these compelling data are anticipated to form a crucial foundation for the forthcoming BLA submission. Meanwhile, Cohort 2 of the SPEARHEAD-1 trial, currently underway, focuses on adolescent and pediatric synovial sarcoma patients. Initial findings indicate an overall response rate akin to that observed in Cohort 1, fueling hope for broader treatment effectiveness.