A single infusion of modified T cells, afamitresgene autoleucel (afami-cel), leads to tumor shrinkage in about 40% of patients with advanced synovial sarcoma, according to preliminary data from a phase-2 trial. "This agent offers a new and novel approach to treat these types of sarcomas," study investigator Dr. Sandra D'Angelo, with Memorial Sloan Kettering Cancer Center in New York, told Reuters Health by email. "Though the data is still not mature, this decrease in tumor burden seems durable so far. There is a need to continue to monitor the patients that have received the therapy to better understand the duration of response," she said. The early data from the SPEARHEAD-1 trial were released ahead of presentation at the American Society of Clinical Oncology (ASCO) virtual annual meeting. Patients with advanced synovial sarcoma or myxoid/round cell liposarcoma (MRCLS) have a "high unmet" medical need for more effective therapies, Dr. D'Angelo said in a press release issued by Adaptimmune, which is developing the therapy and funded the study. Afami-cel is a genetically modified autologous melanoma-associated antigen 4 (MAGE A4) specific T cell therapy. Afami-cel targets MAGE-A4, which is highly expressed in synovial sarcoma and MRCLS in the context of HLA-A*02. Patients in the trial are between 16 and younger than 75 years old and HLA*02 positive with MAGE-A4 expression in at least 30% of tumor cells that were at least 2+ by immunohistochemistry. All had received prior anthracycline- or ifosfamide-containing therapy. All patients undergo leukapheresis to obtain cells to manufacture afami-cel, followed by lymphodepleting chemotherapy and infusion of the modified T cells. At the time of data cut-off (March 29, 2021), 37 patients had received afami-cel (32 with synovial sarcoma, 5 with MRCLS); four patients were pending first efficacy assessment, and 33 had at least one scan (29 with synovial sarcoma and 4 with MRCLS). The overall response rate was 39% (13/33); 41% (12/29) for synovial sarcoma and 25% (1/4) for MRCLS. Responses were observed across a broad range of MAGE-A4 expression and cell doses, Dr. D'Angelo noted in her ASCO presentation. Of the 29 patients with synovial sarcoma with at least one scan, two had complete responses and 10 partial responses; 13 had stable disease and four had progressive disease. The disease control rate was 86%. To date, the safety profile of afami-cel has been favorable, with mainly low-grade cytokine release syndrome and tolerable and reversible hematologic toxicities, Dr. D'Angelo noted. "Most patients experience side effects related to the use of high dose chemotherapy, including decrease in white blood cells, red blood cells and platelets. Most patients fully recover within a one to two weeks from the infusion of the chemotherapy," Dr. D'Angelo told Reuters Health. "In addition, many patients also experience cytokine release syndrome (CRS), which is a reflection of the immune system reacting to the presence of the genetically modified T cells (i.e. afami-cel). CRS can manifest a number of different ways including fever, chills, skin rash, rapid heart rate, shortness of breath. Using tocilizumab can immediately improve CRS," she noted. About 90 patients are planned to be treated as part of the SPEARHEAD-1 trial: 45 in cohort one and 45 in cohort two. Enrollment in cohort one is complete, and cohort two is currently recruiting. In a statement, Adrian Rawcliffe, Adaptimmune CEO, said, "We have shown a high response rate and these responses are still evolving in many patients with increasing depths of response over time and encouraging durability. I am confident that SPEARHEAD-1 will support our BLA (biologics license application) submission next year and offer a life-changing treatment for people with synovial sarcoma." Adaptimmune is funding the SPEARHEAD-1 trial. Dr. D'Angelo has disclosed financial relationships with the company. —Megan Brooks Source
