Afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma (SPEARHEAD-1): An international, open-label, phase 2 trial Journal Article
| Authors: | D'Angelo, S. P.; Araujo, D. M.; Abdul Razak, A. R.; Agulnik, M.; Attia, S.; Blay, J. Y.; Carrasco Garcia, I.; Charlson, J. A.; Choy, E.; Demetri, G. D.; Druta, M.; Forcade, E.; Ganjoo, K. N.; Glod, J.; Keedy, V. L.; Le Cesne, A.; Liebner, D. A.; Moreno, V.; Pollack, S. M.; Schuetze, S. M.; Schwartz, G. K.; Strauss, S. J.; Tap, W. D.; Thistlethwaite, F.; Valverde Morales, C. M.; Wagner, M. J.; Wilky, B. A.; McAlpine, C.; Hudson, L.; Navenot, J. M.; 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, B. A. |
| Article Title: | Afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma (SPEARHEAD-1): An international, open-label, phase 2 trial |
| Abstract: | 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) overall, 39% (17 of 44; 24–55) for patients with synovial sarcoma, and 25% (two of eight; 3–65) for patients with myxoid round cell liposarcoma. Cytokine release syndrome occurred in 37 (71%) of 52 of patients (one grade 3 event). Cytopenias were the most common grade 3 or worse adverse events (lymphopenia in 50 [96%], neutropenia 44 [85%], leukopenia 42 [81%] of 52 patients). No treatment-related deaths occurred. Interpretation: Afami-cel treatment resulted in durable responses in heavily pre-treated patients with HLA-A*02 and MAGE-A4-expressing synovial sarcoma. This study shows that T-cell receptor therapy can be used to effectively target solid tumours and provides rationale to expand this approach to other solid malignancies. Funding: Adaptimmune. © 2024 Elsevier Ltd |
| Keywords: | immunohistochemistry; adult; clinical article; controlled study; human tissue; treatment response; middle aged; major clinical study; overall survival; genetics; fludarabine; clinical trial; neutropenia; doxorubicin; solid tumor; chemotherapy; cancer staging; neurotoxicity; follow up; antineoplastic agent; t lymphocyte; quality control; progression free survival; phase 2 clinical trial; anemia; leukopenia; thrombocytopenia; antineoplastic combined chemotherapy protocols; protein binding; cytogenetics; cyclophosphamide; ifosfamide; docetaxel; protein tyrosine kinase inhibitor; lymphocytopenia; immunotherapy; pazopanib; single drug dose; cell therapy; synovial sarcoma; sarcoma, synovial; corticosteroid; anthracycline; hla a antigen; cytopenia; ethnicity; hla-a antigens; liposarcoma; hispanic; myxosarcoma; melanoma antigen 4; leukapheresis; cytokine release syndrome; overall response rate; liposarcoma, myxoid; tocilizumab; humans; human; male; female; article; afamitresgene autoleucel |
| Journal Title: | Lancet |
| Volume: | 403 |
| Issue: | 10435 |
| ISSN: | 0140-6736 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2024-04-13 |
| Start Page: | 1460 |
| End Page: | 1471 |
| Language: | English |
| DOI: | 10.1016/s0140-6736(24)00319-2 |
| PUBMED: | 38554725 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- MSK corresponding author is Sandra D'Angelo -- Source: Scopus |
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