PO.CL05.03 · 临床研究
瘤内(IT)注射ruxotemitide(LTX-315)联合pembrolizumab治疗对PD-1/PD-L1疗法难治的不可切除晚期黑色素瘤患者：ATLAS-IT-05研究的最终结果
Intratumoral (IT) ruxotemitide (LTX‑315) in combination with pembrolizumab in patients with unresectable advanced melanoma refractory to PD-1/PD-L1 therapy: Final results from the ATLAS-IT-05 study
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：对既往免疫疗法难治的晚期不可切除皮肤黑色素瘤预后差且治疗选择有限。Ruxotemitide是一种溶瘤肽，可诱导免疫原性细胞死亡并重塑肿瘤微环境以增强抗肿瘤免疫。临床前和早期临床数据支持其与PD-1阻断的协同作用。这项2期研究评估了瘤内(IT)注射ruxotemitide联合pembrolizumab治疗既往检查点抑制剂(CPI)治疗失败后、可行IT注射的不可切除晚期或转移性黑色素瘤患者。
方法：这是一项开放标签、单臂2期研究，入组患有IIIB-IV期(M1b)皮肤黑色素瘤且至少有一处可注射病灶(皮肤、皮下、淋巴结或肌肉内)的成人。患者接受IT注射ruxotemitide(前29天内最多七次注射)联合pembrolizumab 200 mg静脉注射每3周一次，直至疾病进展或最长24个月。主要终点为按RECIST v1.1评估的客观缓解率(ORR)。次要终点包括缓解持续时间(DoR)、无进展生存期(PFS)和安全性。
结果：入组23例患者，中位年龄68岁(范围42-91岁)。超过半数(52.1%)患者既往接受过三线或以上治疗，且所有患者既往均接受过CPI治疗。22例患者可评估疗效。ORR为13.6%(80% CI, 5.1-27.9)。临床获益率为36.4%。所有缓解均持久，持续超过24个月。中位PFS为6.3个月。安全性特征与IT免疫疗法和pembrolizumab的已知效应一致。最常见的治疗中出现的不良事件(TEAE)为注射部位反应(95.7%)、疲乏(30%)、瘙痒(26.1%)、低血压(26.1%)和贫血(21.7%)。无TEAE导致治疗中止。
结论：在既往经过大量治疗、CPI难治的晚期或转移性黑色素瘤伴可注射病灶患者中，IT注射ruxotemitide联合pembrolizumab表现出持久的抗肿瘤活性和可控的安全性。这些发现支持进一步在黑色素瘤中对该联合方案进行临床评估。
查看英文原文 English abstract
Background: Advanced unresectable cutaneous melanoma refractory to prior immunotherapy is associated with poor prognosis and limited treatment options. Ruxotemitide, an oncolytic peptide, induces immunogenic cell death and remodels the tumor microenvironment to enhance antitumor immunity. Preclinical and early clinical data support synergistic activity with PD-1 blockade. This Phase 2 study evaluated intratumoral (IT) ruxotemitide in combination with pembrolizumab in patients with unresectable advanced or metastatic melanoma accessible for IT injection after prior checkpoint inhibitor (CPI) failure.
Methods: This was an open-label, single-arm Phase 2 study enrolling adults with stage IIIB-IV (M1b) cutaneous melanoma and at least one injectable lesion (cutaneous, subcutaneous, lymph node, or intramuscular). Patients received IT ruxotemitide (up to seven injections during the first 29 days) in combination with pembrolizumab 200 mg IV every 3 weeks until disease progression or for up to 24 months. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), and safety.
Results: Twenty-three patients were enrolled, with a median age of 68 years (range, 42-91 years). Over half (52.1%) of pts had received three or more prior lines of therapy, and all had previous CPI treatment. Twenty-two patients were evaluable for efficacy. ORR was 13.6% (80% CI, 5.1-27.9). The clinical benefit rate was 36.4%. All responses were durable, lasting more than 24 months. Median PFS was 6.3 months. The safety profile was consistent with known effects of IT immunotherapy and pembrolizumab. The most common treatment emergent adverse events (TEAEs) were injection-site reactions (95.7%), fatigue (30%), pruritus (26.1%), hypotension (26.1%), and anemia (21.7%). No TEAEs led to treatment discontinuation.
Conclusions: IT ruxotemitide plus pembrolizumab demonstrated durable antitumor activity and manageable safety in heavily pretreated patients with CPI-refractory advanced or metastatic melanoma with injectable disease. These findings support further clinical evaluation of this combination in melanoma.
利益披露 Disclosure
S. Dalle, None..
A. Diab, None..
M. F. Sanmamed, None..
L. Mortier, None.
M. Gil,
Lilly Stock.
Ø. Rekdal, None.
K. A. Benhadji,
Lilly Stock.