Patients with metastatic or unresectable synovial sarcoma or myxoid round cell liposarcoma (comprising 5–10% of all soft-tissue sarcomas) typically have limited long-term survival, especially after disease recurrence on first-line therapy. Now, data from the phase II SPEARHEAD-1 trial testing afamitresgene autoleucel (afami-cel), a CD4⁺ and CD8⁺ T cell product transduced with an affinity-enhanced MAGE-A4-specific T cell receptor, provide promising evidence of safety and efficacy in this setting.

At a median follow-up duration of 32.6 months, ORR was 37% (95% CI 24–51%), thus exceeding the prespecified null hypothesis (ORR of 18%) and meeting the primary end point. No complete responses were observed. ORRs for patients with synovial sarcoma (n = 44) and myxoid round cell liposarcoma (n = 8) were 39% and 25%, respectively. These patients had median response durations of 11.6 months and 4.2 months. Median progression-free survival in the entire cohort was 3.7 months and median overall survival 16.9 months. Not requiring bridging therapy, a MAGE A4 expression H score of ≥200 and a baseline sum of target lesions of <100 mm were all associated with improved ORRs.

患有转移性或不可切除的滑膜肉瘤或粘液样圆细胞脂肪肉瘤（占所有软组织肉瘤的 5-10%）的患者通常长期生存有限，特别是在一线治疗后疾病复发后。现在，来自 II 期 SPEARHEAD-1 试验的数据测试了 afamitresgene autoleucel (afami-cel)，这是一种用亲和力增强的 MAGE-A4 特异性 T 细胞受体转导的 CD4 ⁺和 CD8 ⁺ T 细胞产品，提供了有希望的安全性和安全性证据。在此设置下的功效。

中位随访时间为 32.6 个月，ORR 为 37%（95% CI 24-51%），从而超过了预先设定的零假设（ORR 为 18%）并达到了主要终点。没有观察到完整的反应。滑膜肉瘤 ( n  = 44) 和粘液样圆细胞脂肪肉瘤 ( n = 8)患者的 ORR 分别为 39% 和 25%。这些患者的中位缓解持续时间分别为 11.6 个月和 4.2 个月。整个队列的中位无进展生存期为 3.7 个月，中位总生存期为 16.9 个月。不需要桥接治疗，MAGE A4 表达H评分≥200 和目标病灶基线总和 <100 mm 均与 ORR 改善相关。