FDA Clears Companion Diagnostic for Afami-Cel in Pretreated Metastatic Synovial Sarcoma

The FDA has granted 510(k) clearance to the SeCore^™ CDx HLA A Sequencing System for use as a companion diagnostic for afamitresgene autoleucel (afami-cel; Tecelra) in select adult patients with unresectable or metastatic synovial sarcoma.¹

On August 1, 2024, the FDA granted accelerated approval to afami-cel 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.² This marked the first approval of an engineered cell therapy for the treatment of patients with solid tumors.

“We are thrilled to expand the labeling of our companion diagnostic SeCore CDx HLA A Sequencing System to include [afami-cel] and to support clinicians in identifying which patients may benefit from this first-of-its-kind treatment,” Tina Liedtky, president of Transplant Diagnostics at Thermo Fisher Scientific, stated in a news release.¹ “Our knowledge of the human immune system and how it might impact treatment options across the healthcare continuum continues to evolve. We look forward to ongoing opportunities to collaborate with innovative companies like Adaptimmune to expand patient access to breakthrough treatments that improve quality of life.”

The regulatory agency’s accelerated approval of afami-cel was based on findings from cohort 1 of the phase 2 SPEARHEAD-1 trial (NCT04044768). Patients treated with afami-cel (n = 44) experienced an overall response rate (ORR) of 43% per independent review assessment, including a complete response rate of 4.5%. The median duration of response (DOR) was 6 months (95% CI, 4.6-not reached [NR]), and the 12-month DOR rate was 39%.²

Cohort 1 of the open-label, nonrandomized SPEARHEAD-1 trial enrolled patients between 16 and 75 years of age with cytogenetically confirmed metastatic or unresectable synovial sarcoma or myxoid round cell liposarcoma. 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 HLA-A*02:05. Additionally, a MAGE-A4 staining intensity of 2 or higher in at least 30% of tumor cells per an immunohistochemistry assay was required.³

Other key inclusion criteria consisted of prior treatment with a regimen containing an anthracycline or ifosfamide, measurable disease per RECIST 1.1 criteria, an ECOG performance status 0 or 1, and adequate organ function.

After enrolled patients underwent leukapheresis, they received lymphodepletion with fludarabine at 30 mg/m² on days −7 to −4 and cyclophosphamide at 600 mg/m² on days −5 to −3 prior to the administration of a single infusion of afami-cel on day 1 at a target dose of 1.0 × 10⁹ to 10.0 × 10⁹ T cells. Notably, patients were allowed to receive bridging therapy between leukapheresis and lymphodepletion at investigator discretion. Use of tocilizumab (Actemra) was permitted 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 from SPEARHEAD-1 published in Lancet demonstrated that in patients with synovial sarcoma who experienced a response, treatment with afami-cel led to a median overall survival (OS) that was NR (95% CI, 15.4–not evaluable). The estimated 12- and 24-month OS rates for this population were 90% (95% CI, 65%-99%) and 70% (95% CI, 43%-87%), respectively.

Regarding safety, CRS occurred in 71% of evaluable patients (n = 52); however, only 1 patient experienced a grade 3 event. The most common grade 3 or higher adverse effects included lymphopenia (96%), neutropenia (85%), and leukopenia (81%). No treatment-related deaths were reported.

References

1. FDA grants Thermo Fisher Scientific SeCore HLA typing kit 510(k) clearance for use as companion diagnostic with a T-cell receptor therapy for synovial sarcoma. News release. Thermo Fisher Scientific. August 6, 2024. Accessed August 6, 2024. https://newsroom.thermofisher.com/newsroom/press-releases/press-release-details/2024/FDA-Grants-Thermo-Fisher-Scientific-SeCore-HLA-Typing-Kit-510k-Clearance-for-Use-as-Companion-Diagnostic-with-a-T-Cell-Receptor-Therapy-for-Synovial-Sarcoma/default.aspx
2. Adaptimmune receives US 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
3. 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