FDA Approves Adaptimmune’s TCR T-cell Therapy Afami-cel for Synovial Sarcoma
It is the first engineered T-cell therapy to be approved by the FDA for a solid tumor indication.
Brian Van Tine, MD, PhD
This is a developing story and will be updated with new information as it becomes available.
The FDA has granted accelerated approval to Adaptimmune Therapeutics’ afamitresgene autoleucel (afami-cel, formerly ADP-A2M4), an investigational T-cell receptor (TCR) T-cell therapy marketed as Tecelra, for the treatment of synovial sarcoma (SS).1 It is the first engineered T-cell therapy to be approved by the FDA for a solid tumor indication, indicated specifically 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 tumor expresses the MAGE-A4 antigen as determined by FDA authorized companion diagnostic devices.
“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 tumor growth and progression,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research (CBER), said in a statement.1 “The approval of this state-of-the-art immunotherapy technology provides a critical new option for a patient population in need and demonstrates the FDA’s dedication to the advancement of beneficial cancer treatments.”
Sandra D’Angelo, MD, Sarcoma Medical Oncologist and Cell Therapist, Memorial Sloan Kettering Cancer Center, and the SPEARHEAD clinical trial's principal investigator, noted that the therapy "uses each patient’s own immune cells to recognize and attack their cancer cells in a one-time infusion treatment" and "is significantly different than the current standards of care for advanced synovial sarcoma." She added that the FDA decision "represents a much-needed new option for people diagnosed with this sarcoma and an important milestone for the use of cell therapies in solid tumor cancers.”
The FDA’s decision was based on data from cohort 1 of the pivotal SPEARHEAD-1 clinical trial (NCT04044768), which met its primary efficacy endpoint of overall objective response (ORR) compared to natural history.3 Adaptimmune previously announced data from the trial that showed a 39% ORR and a median duration of response of around 12 months. Furthermore, patients treated with afami-cel showed a median overall survival (OS) of approximately 17 months; by contrast, patients with SS that have received at least 2 prior lines of therapy had a median OS of less than 12 months according to natural history data.4 The number of prior lines of therapy received by patients in SPEARHEAD-1 ranged from 1-12 (median, 3). Notably, at 2 years posttreatment, 70% of patients who responded to afami-cel in SPEARHEAD-1 remained alive. The safety profile for afami-cel in the trial was characterized as manageable and in line with expectations.
Adrian Rawcliffe, Adaptimmune's Chief Executive Officer, said in a statement that, "The approval of Tecelra is a momentous step in Adaptimmune’s journey to redefine the way cancer is treated and the culmination of a decade of groundbreaking R&D. I want to thank the patients, caregivers, investigators, and clinical teams as well as everyone at Adaptimmune and our partners who made possible this watershed moment for cell therapy and for people with synovial sarcoma. We are committed to advancing our robust clinical pipeline to serve more patients in need and plan to progress lete-cel, the next late-stage investigational treatment in our sarcoma franchise, with a rolling BLA submission to the FDA next year.”
Afami-cel, which is delivered as a single dose, targets MAGE-A4.5 The biologics license application leading to today’s decision was submitted to the FDA in December 2023 and accepted by the agency with priority review in January 2024.
“For synovial sarcoma in the metastatic setting, we've been using the same drugs for quite a while…,” John A. Charlson, MD, associate professor of medicine, Medical College of Wisconsin, and primary investigator of SPEARHEAD-1, told CGTLive® during an interview earlier this year focused on the then-upcoming FDA decision. “Some standard cytotoxic chemotherapies have activity for some patients that can be effective... But we haven’t had a lot of new therapies in recent years. So, this T-cell therapy, afami-cel, is essentially a version of immunotherapy, and it’s exciting to see how we're building all these different ways to capture the activity of the immune system against cancers.”
