The FDA has granted accelerated approval for afamitresgene autoleucel (afami-cel) for advanced synovial sarcoma. Phase 2 trial data showed a 43% overall response rate, with manageable safety profiles.
United States: The FDA has granted accelerated approval for afamitresgene autoleucel (afami-cel; Tecelra) to treat adult patients with unresectable or metastatic synovial sarcoma who have previously undergone chemotherapy. Eligibility for treatment includes patients who are positive for HLA-A02:01P, -A02:02P, -A02:03P, or -A02:06P and whose tumors express MAGE-A4, as confirmed by FDA-approved or -cleared companion diagnostic devices.
This regulatory decision was supported by data from cohort 1 of the Phase 2 SPEARHEAD-1 trial (NCT04044768). The trial demonstrated that 43% of patients treated with afami-cel (n = 44) achieved an overall response rate (ORR) as assessed by independent review, with a complete response rate of 4.5%. The median duration of response (DOR) was 6 months (95% CI, 4.6–not reached), and the 12-month DOR rate was 39%.
Cohort 1 of the open-label, nonrandomized SPEARHEAD-1 trial included patients aged 16 to 75 with metastatic or unresectable synovial sarcoma or myxoid round cell liposarcoma, confirmed by cytogenetics to express MAGE-A4. Patients were required to have HLA-A02:01, HLA-A02:02, HLA-A02:03, HLA-A02:06, or other HLA-A02 alleles, excluding HLA-A02:05, and must have had at least one prior line of anthracycline- or ifosfamide-containing chemotherapy. Additional inclusion criteria included measurable disease per RECIST 1.1, an ECOG performance status of 0 or 1, and adequate organ function.
Following leukapheresis, patients underwent lymphodepletion with fludarabine and cyclophosphamide, followed by afami-cel infusion at a target dose of 1.0 × 10^9 to 10.0 × 10^9 T cells. Bridging therapy was permitted between leukapheresis and lymphodepletion, and treatment with tocilizumab (Actemra) was allowed for grade 1 cytokine release syndrome (CRS) if symptoms persisted for at least 24 hours or if patients had comorbidities.
The primary endpoint of the trial was ORR per RECIST 1.1 criteria. Additional data published in The Lancet revealed a median overall survival (OS) that was not reached (95% CI, 15.4–not estimable) for patients with synovial sarcoma who responded to treatment. The estimated 12- and 24-month OS rates for responders were 90% (95% CI, 65%-99%) and 70% (95% CI, 43%-87%), respectively.
Regarding safety, all 52 patients treated with afami-cel experienced any-grade treatment-emergent adverse effects, with 92% of patients having adverse events related to the therapy. CRS of any grade occurred in 71% of patients, with 2% experiencing grade 3 CRS, and no grade 4 events reported. The median time to onset of CRS was 2 days (interquartile range [IQR], 2-3), and the median time to resolution was 3 days (IQR, 2-5). Tocilizumab was administered to 19 patients, with 2 requiring corticosteroids. All CRS cases resolved. Additionally, one patient experienced grade 1 immune effector cell–associated neurotoxicity syndrome along with CRS, which resolved one day later.
Adrian Rawcliffe, chief executive officer of Adaptimmune Therapeutics, stated, "The approval of [afami-cel] 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.”
According to TechSci Research, the FDA's accelerated approval of afamitresgene autoleucel (afami-cel) for advanced synovial sarcoma is poised to significantly impact the healthcare market. This approval provides a new, advanced treatment option for a rare and challenging cancer, addressing a critical unmet need for patients with unresectable or metastatic synovial sarcoma who have exhausted conventional therapies. By offering a targeted therapy with demonstrated efficacy, afami-cel not only expands the therapeutic arsenal but also sets a precedent for the application of cell therapies in rare cancers. This development could drive further investment and research into innovative treatments, potentially accelerating the growth of the cell and gene therapy sector. Additionally, the approval could lead to increased market competition, pushing other pharmaceutical companies to accelerate their development of similar advanced therapies.