FDA Grants Accelerated Approval to Afami-Cel for Advanced Synovial Sarcoma

FDA

The FDA has granted accelerated approval to afamitresgene autoleucel (afami-cel; Tecelra) for the treatment of adult patients with unresectable or metastatic synovial sarcoma who have received prior chemotherapy; are HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive; and whose tumors express MAGE-A4, as determined by FDA-approved or -cleared companion diagnostic devices.

The regulatory decision was supported by data from cohort 1 of the phase 2 SPEARHEAD-1 trial (NCT04044768), which showed that patients treated with afami-cel (n = 44) achieved an overall response rate (ORR) of 43% per independent review assessment, and the complete response rate was 4.5%. Furthermore, the median duration of response (DOR) was 6 months (95% CI, 4.6–not reached [NR]), and the 12-month DOR rate was 39%.

"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," Adrian Rawcliffe, chief executive officer of Adaptimmune Therapeutics, stated in a news release. "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.”

Cohort 1 of the open-label, nonrandomized SPEARHEAD-1 trial enrolled patients between 16 and 75 years of age with metastatic or unresectable synovial sarcoma or myxoid round cell liposarcoma as confirmed by cytogenetics that expressed MAGE-A4. Patients needed to be positive for HLA-A*02:01, HLA-A*02:02, HLA-A*02:03, HLA-A*02:06, or other HLA-A*02 alleles, excluding excluding HLA-A*02:05. At least 1 prior line of anthracycline- or ifosfamide-containing chemotherapy. Other key inclusion criteria consisted of measurable disease per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, and adequate organ function.²

Following leukapheresis, enrolled patients underwent lymphodepletion with fludarabine at 30 mg/m² on days −7 to −4 and cyclophosphamide at 600 mg/m² on days −5 to −3. Afami-cel was given on day 1 at a target dose of 1.0 × 10⁹ to 10.0 × 10⁹ T cells. Bridging therapy was permitted at investigator discretion between leukapheresis and lymphodepletion, and treatment with tocilizumab (Actemra) was allowed for grade 1 cytokine release syndrome (CRS) following the infusion of afami-cel if patients had symptoms that lasted for at least 24 hours or had comorbidities.

ORR per RECIST 1.1 criteria served as the trial's primary end point.

Additional data published in Lancet showed that the median overall survival (OS) was NR (95% CI, 15.4–not estimable) in patients with synovial sarcoma who experienced response. The estimated 12- and 24-month OS rates for responders in this population were 90% (95% CI, 65%-99%) and 70% (95% CI, 43%-87%), respectively.

Regarding safety, all treated patients with synovial sarcoma or myxoid round cell liposarcoma (n = 52) experienced any-grade treatment-emergent adverse effects, and 92% of patients had AEs related to afami-cel.

Any-grade CRS was reported in 71% of patients, although 2% of patients had grade 3 CRS, and no grade 4 events were reported. The median time to onset of CRS was 2 days (interquartile range [IQR], 2-3), and the median time to resolution of CRS was 3 days (IQR, 2-5). Notably, 19 patients received tocilizumab, and 2 of these patients also needed corticosteroids. All CRS cases were resolved. One patient experienced grade 1 immune effector cell–associated neurotoxicity syndrome and concomitant CRS, and in this patient, neurotoxicity syndrome resolved 1 day later.

References

1. Adaptimmune receives U.S. FDA accelerated approval of Tecelra (afamitresgene autoleucel), the first approved engineered cell therapy for a solid tumor. News release. Adaptimmune Therapeutics. August 1, 2024. Accessed August 2, 2024. https://www.adaptimmune.com/investors-and-media/news-center/press-releases/detail/271/adaptimmune-receives-u-s-fda-accelerated-approval-of
2. D'Angelo SP, Araujo DM, Abdul Razak AR, et al. Afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma (SPEARHEAD-1): an international, open-label, phase 2 trial. Lancet. 2024;403(10435):1460-1471. doi:10.1016/S0140-6736(24)00319-2