Pooled analyses of clinical outcomes with afamitresgene autoleucel (afami-cel) in metastatic synovial sarcoma.
Year: 2026
Type: conference-abstract
Abstract: 11505 Background: Afamitresgene autoleucel (afami-cel) is a melanoma-associated antigen A4 (MAGEA4)-directed genetically modified autologous T cell immunotherapy consisting of CD4 and CD8 positive T cells transduced with a self-inactivating lentiviral vector (LV) expressing an affinity-enhanced T cell receptor (TCR) specific for the human MAGE-A4. Here we report the pooled results of afami-cel in phase 1 and phase 2 trials in patients (pts) with advanced (unresectable/metastatic) synovial sarcoma (SyS). Methods: Pts who were HLA-A*02 positive with previously treated, advanced SyS positive for MAGE-A4 received afami-cel after lymphodepleting chemotherapy containing fludarabine and cyclophosphamide. The pooled analyses evaluated overall response rate (ORR) per RECIST v1.1 by investigator review, duration of response (DoR), ORR in sub-populations, overall survival (OS), safety and pharmacokinetics. Results: As of May 2025, 153 pts with advanced SyS received afami-cel (1.00 –9.99×10 9 MAGE-A4 TCR positive T cells). The median age was 40 years (range: 13–76 years), 54% of pts were male, and 86% of pts were white. The median MAGE-A4 expression by H-score was 256.0 (range: 60–300). All pts received prior anthracycline and/or ifosfamide therapy and received a median of 2 prior lines of therapy (range: 1–12). ORR by investigator review was 43.8% (95% CI 35.8, 52.0). Responses were observed across all subgroups, including pediatric SyS pts. The median DoR was 7.1 months (95% CI 4.7, 10.6) and ranged from 1 to 58+ months. Median OS was 18.7 months (95% CI: 14.1, 22.5) with 44% of pts censored at the data cut-off. The 12-month or longer and 24-month or longer OS probabilities were 64.4% and 40.5%, respectively. Among the 67 pts who had a RECIST response, the median OS was 37.5 months (95% CI 26.3, 50.5). The most common any-grade non-laboratory TEAEs (≥20% of pts) were cytokine release syndrome (CRS) (73.2%), nausea (64.1%), fatigue (45.8%), pyrexia (33.3%), vomiting (29.4%), constipation (28.1%), diarrhea (27.1%), headache (26.8%), and cough (20.9%). The most common Grade ≥3 laboratory TEAEs (≥20% of pts) were lymphopenia, neutropenia, leukopenia, and anemia. Afami-cel persisted long-term, including >3 years. Conclusions: To the best of our knowledge, this is the largest dataset of T-cell therapy treated pts with advanced SyS. The magnitude of ORR supported by DOR demonstrated with afami-cel treatment is considered clinically meaningful in this rare pt population with a poor prognosis and limited effective therapies. CRS and cytopenias were common and manageable. Pts with advanced SyS treated with afami-cel had encouraging survival, especially those pts with a RECIST response. Clinical trial information: NCT04044768 , NCT03132922
Source: Journal of Clinical Oncology
Authors: Sandra P. D'Angelo, Dejka M. Araujo, Abdul Razak, Mark Agulnik, Marcus O. Butler, Mihaela Druta, Edouard Forcade, Kristen Nooshin Ganjoo, Axel Le Cesne, Scott Michael Schuetze, Sandra Strauss, Fiona Thistlethwaite, Claudia Valverde, Michael J. Wagner, Michael Jason Nathenson, Jane Bai, Dennis Williams, Erin Van Winkle, Stuart McPherson, Jean-Yves Blay
Institutions: Memorial Sloan Kettering Cancer Center, The University of Texas MD Anderson Cancer Center, University Health Network, University of Southern California, University of Toronto, Princess Margaret Cancer Centre, Moffitt Cancer Center, Centre Hospitalier Universitaire de Bordeaux, Stanford Cancer Institute, Stanford University, Institut Gustave Roussy, University of Michigan, University College London, University of Manchester, The Christie NHS Foundation Trust, Vall d'Hebron Hospital Universitari, Dana-Farber Cancer Institute, US WorldMeds (United States), Adaptimmune (United Kingdom), Centre Léon Bérard
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W7162514152