Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland.
Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland.
Clin Cancer Res. 2024 Sep 3;30(17):3715-3725. doi: 10.1158/1078-0432.CCR-23-3874.
TILT-123 (igrelimogene litadenorepvec) is an oncolytic adenovirus armed with TNFa and IL2, designed to induce T-cell infiltration and cytotoxicity in solid tumors.
TUNIMO (NCT04695327) was a single-arm, multicenter phase I dose-escalation trial designed to assess the safety of TILT-123 in advanced solid cancers refractory to standard therapy. Patients received intravenous and intratumoral TILT-123. The primary endpoint was safety by adverse events (AE), laboratory values, vital signs, and electrocardiograms. Secondary endpoints included tumor response, pharmacokinetics, and predictive biomarkers.
Twenty patients were enrolled, with a median age of 58 years. Most prevalent cancer types included sarcomas (35%), melanomas (15%) and ovarian cancers (15%). No dose-limiting toxicities were observed. The most frequent treatment-related AEs included fever (16.7%), chills (13.0%), and fatigue (9.3%). Ten patients were evaluable for response on day 78 with RECIST 1.1, iRECIST or PET-based evaluation. The disease control rate by PET was 6/10 (60% of evaluable patients) and 2/10 by RECIST 1.1 and iRECIST(20%of evaluable patients). Tumor size reductions occurred in both injected and non-injected lesions. TILT-123 was detected in injected and non-injected tumors, and virus was observed in blood after intravenous and intratumoral injections. Treatment resulted in reduction of lymphocytes in blood, with concurrent lymphocyte increases in tumors, findings compatible with trafficking.
TILT-123 was safe and able to produce antitumor effects in local and distant lesions in heavily pre-treated patients. Good tolerability of TILT-123 facilitates combination studies, several of which are ongoing (NCT04217473, NCT05271318, NCT05222932, and NCT06125197). See related commentary by Silva-Pilipich and Smerdou, p. 3649.
TILT-123（igrelimogene litadenorepvec）是一种携带 TNFa 和 IL2 的溶瘤腺病毒，旨在诱导实体瘤中的 T 细胞浸润和细胞毒性。
TUNIMO（NCT04695327）是一项单臂、多中心的 I 期剂量递增试验，旨在评估晚期实体癌患者对标准治疗耐药时，静脉内和肿瘤内注射 TILT-123 的安全性。患者接受静脉内和肿瘤内注射 TILT-123。主要终点为不良事件（AE）、实验室值、生命体征和心电图评估的安全性。次要终点包括肿瘤反应、药代动力学和预测性生物标志物。
20 例患者入组，中位年龄 58 岁。最常见的癌症类型包括肉瘤（35%）、黑色素瘤（15%）和卵巢癌（15%）。未观察到剂量限制性毒性。最常见的治疗相关 AE 包括发热（16.7%）、寒战（13.0%）和疲劳（9.3%）。10 例患者在第 78 天接受 RECIST 1.1、iRECIST 或基于 PET 的评估，可评估疾病反应。根据 PET 评估的疾病控制率为 6/10（10 例可评估患者中的 60%），根据 RECIST 1.1 和 iRECIST 评估的为 2/10（10 例可评估患者中的 20%）。注射和未注射病灶均出现肿瘤缩小。TILT-123 在注射和未注射肿瘤中均被检测到，静脉内和肿瘤内注射后在血液中观察到病毒。治疗导致血液中淋巴细胞减少，同时肿瘤中淋巴细胞增加，这些发现与细胞转移相符。
TILT-123 是安全的，能够在预处理过的患者的局部和远处病灶中产生抗肿瘤作用。TILT-123 的良好耐受性有利于联合研究，目前正在进行几项研究（NCT04217473、NCT05271318、NCT05222932 和 NCT06125197）。请参阅 Silva-Pilipich 和 Smerdou 的相关评论，第 3649 页。
