FDA Clears SeCore CDx as Companion Diagnostic for Afami-cel in Synovial Sarcoma
The FDA has granted 510(k) clearance to the SeCore™ CDx HLA A sequencing system as companion diagnostic for afamitresgene autoleucel in synovial sarcoma, paving the way for a first-of-its-kind solid tumor therapy.
The SeCore™ CDx HLA A Sequencing System has gained 510(k) clearance from the FDA as a companion diagnostic for afamitresgene autoleucel (afami-cel; Tecelra) when used for the treatment of adult patients with unresectable or metastatic synovial sarcoma.1
Afami-cel, a novel engineered T-cell therapy that targets the MAGE-A4 protein, was granted accelerated approval from the FDA on August 1, 2024, for the treatment of adult patients with unresectable or metastatic synovial sarcoma given prior chemotherapy. These patients are required to be HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive and have tumors that express MAGE-A4, as determined by FDA-approved or -cleared companion diagnostic devices.2
This approval is the first of its kind for the treatment of patients with solid tumors.
“This is very exciting. [The approval] is first-in-class, if you think of solid tumors as a class, and it is 1 of the leaders for T-cell therapy in solid tumors,” said Edwin Choy, MD, PhD, director of the sarcoma program in the Division of Hematology Oncology at Massachusetts General Hospital, a founding member of Mass General Brigham, and associate professor of medicine at Harvard Medical School, in an interview with Targeted OncologyTM.
“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,” said Tina Liedtky, president of transplant diagnostics at Thermo Fisher Scientific, in a press 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.”
About the Phase 2 SPEARHEAD-1 Study of Afami-Cel
The regulatory decision was supported by results from cohort 1 of the phase 2 SPEARHEAD-1 trial (NCT04044768). At a median follow-up of 32.6 months (IQR, 29.4-36.1), the overall response rate (ORR) among all patients was 37% (95%, CI 24%-51%), 39% (95% CI, 24%-55%) for patients with synovial sarcoma, and 25% (95% CI, 3%-65%) for patients with myxoid round cell liposarcoma.3
The single-arm, open-label, phase 2 SPEARHEAD-1 study included 52 patients who had cytogenetically confirmed synovial sarcoma (n = 44) or myxoid round cell liposarcoma (n = 8). Patients were enrolled between December 17, 2019, and July 27, 2021.4
Enrollment was open to patients with measurable disease who had received prior treatment with an anthracycline- or ifosfamide-containing regimen and had an ECOG performance status of 0 or 1. Patients were required to have tested positive for HLA-A*02:01, HLA-A*02:02, HLA-A*02:03, or HLA-A*02:06, and have MAGE-A4 expression of 1 or greater staining in at least 10% of cells by immunohistochemistry. In cohort 1, patients received afami-cel. Those enrolled in this cohort were heavily pretreated with a median of 3 prior lines of systemic therapy (IQR, 2-4).
Investigators evaluated the primary end point of ORR and the secondary end points of treatment-related adverse events, safety, measurement of T-cell clonality and insertional oncogenesis in peripheral blood mononuclear cells (PBMCs), best overall response, time to response, duration of response, progression-free survival, overall survival, quantitation of genetically engineered T-cells in PBMCs, time taken to achieve peak expansion of genetically engineered T-cells in PBMCs by flow cytometry, and in vitro diagnostic assay for screening.
Additional findings showed that 37 patients (71%) had cytokine release syndrome, 1 of which was grade 3.3 The most common grade 3 or greater adverse event was cytopenia, with lymphopenia seen in 96% of patients, neutropenia in 85%, and leukopenia in 81%. Moreover, there were no treatment-related deaths.
