| Title: |
Afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma (SPEARHEAD-1): an international, open-label, phase 2 trial |
| Authors: |
D'Angelo, SP; Araujo, DM; Abdul Razak, AR; Agulnik, M; Attia, S; Blay, JY; Carrasco Garcia, I; Charlson, JA; Choy, E; Demetri, GD; Druta, M; Forcade, E; Ganjoo, KN; Glod, J; Keedy, VL; Le Cesne, A; Liebner, DA; Moreno, V; Pollack, SM; Schuetze, SM; Schwartz, GK; Strauss, SJ; Tap, WD; Thistlethwaite, F; Valverde Morales, CM; Wagner, MJ; Wilky, BA; McAlpine, C; Hudson, L; Navenot, JM; Wang, T; Bai, J; Rafail, S; Wang, R; Sun, A; Fernandes, L; Van Winkle, E; Elefant, E; Lunt, C; Norry, E; Williams, D; Biswas, S; Van Tine, BA |
| Source: |
The Lancet , 403 (10435) pp. 1460-1471. (2024) |
| Publisher Information: |
ELSEVIER SCIENCE INC |
| Publication Year: |
2024 |
| Collection: |
University College London: UCL Discovery |
| Description: |
BACKGROUND: Afamitresgene autoleucel (afami-cel) showed acceptable safety and promising efficacy in a phase 1 trial (NCT03132922). The aim of this study was to further evaluate the efficacy of afami-cel for the treatment of patients with HLA-A*02 and MAGE-A4-expressing advanced synovial sarcoma or myxoid round cell liposarcoma. METHODS: SPEARHEAD-1 was an open-label, non-randomised, phase 2 trial done across 23 sites in Canada, the USA, and Europe. The trial included three cohorts, of which the main investigational cohort (cohort 1) is reported here. Cohort 1 included patients with HLA-A*02, aged 16–75 years, with metastatic or unresectable synovial sarcoma or myxoid round cell liposarcoma (confirmed by cytogenetics) expressing MAGE-A4, and who had received at least one previous line of anthracycline-containing or ifosfamide-containing chemotherapy. Patients received a single intravenous dose of afami-cel (transduced dose range 1·0 × 109–10·0 × 109 T cells) after lymphodepletion. The primary endpoint was overall response rate in cohort 1, assessed by a masked independent review committee using Response Evaluation Criteria in Solid Tumours (version 1.1) in the modified intention-to-treat population (all patients who received afami-cel). Adverse events, including those of special interest (cytokine release syndrome, prolonged cytopenia, and neurotoxicity), were monitored and are reported for the modified intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04044768; recruitment is closed and follow-up is ongoing for cohorts 1 and 2, and recruitment is open for cohort 3. FINDINGS: Between Dec 17, 2019, and July 27, 2021, 52 patients with cytogenetically confirmed synovial sarcoma (n=44) and myxoid round cell liposarcoma (n=8) were enrolled and received afami-cel in cohort 1. Patients were heavily pre-treated (median three [IQR two to four] previous lines of systemic therapy). Median follow-up time was 32·6 months (IQR 29·4–36·1). Overall response rate was 37% (19 of 52; 95% CI 24–51) ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10213399/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10213399/1/nihms-1984642.pdf; https://discovery.ucl.ac.uk/id/eprint/10213399/ |
| Rights: |
open |
| Accession Number: |
edsbas.96982D4A |
| Database: |
BASE |