Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
Department of Oncology and Hemato-Oncology, University of Milan, Milano, Italy.
BMJ Open. 2024 Aug 29;14(8):e079132. doi: 10.1136/bmjopen-2023-079132.
This study evaluates the safety/efficacy of sabatolimab plus spartalizumab in patients with melanoma or non-small cell lung cancer (NSCLC).
DESIGN, SETTING AND PARTICIPANTS: This is a phase 1-1b/2, open-label, multinational, multicentre study of patients with advanced/metastatic melanoma or NSCLC with ≥1 measurable lesion.
Patients were given sabatolimab 800 mg every 4 weeks plus spartalizumab 400 mg every 4 weeks until unacceptable toxicity, disease progression and/or treatment discontinuation.
The phase 2 primary outcome measure was overall response rate and secondary objectives included evaluation of the safety, tolerability, efficacy and pharmacokinetics of sabatolimab in combination with spartalizumab.
33 patients (melanoma n=16, NSCLC n=17) received sabatolimab plus spartalizumab. 31 (94%) experienced ≥1 adverse event (AE); 15 (46%) experienced grade 3/4 events. The most frequent grade ≥3 AEs for NSCLC were anaemia, dyspnoea and pneumonia (each n=2, 12%); for patients with melanoma, the most frequent grade ≥3 AEs were physical health deterioration, hypokalaemia, hypophosphataemia, pathological fracture and tumour invasion (each n=1; 6%). One (3%) patient discontinued treatment due to AE. Stable disease was seen in three patients with melanoma (19%) and six patients with NSCLC (35%). Median progression-free survival was 1.8 (90% CI 1.7 to 1.9) and 1.7 (90% CI 1.1 to 3.4) months for patients with melanoma and NSCLC, respectively. Patients with stable disease had higher expression levels of CD8, LAG3, programmed death-ligand 1 and anti-T-cell immunoglobulin and mucin-domain containing-3 at baseline. The pharmacokinetics profile of sabatolimab was consistent with the phase 1 study.
Sabatolimab plus spartalizumab was well tolerated in patients with advanced/metastatic melanoma or NSCLC who had progressed following antiprogrammed death-1/antiprogrammed death-ligand 1 treatment. Limited antitumour activity was observed. The tolerability of sabatolimab administration supports the potential to explore treatment with sabatolimab in various combination regimens and across a spectrum of tumour types.
NCT02608268.
本研究评估了 sabatolimab 联合 spartalizumab 治疗黑色素瘤或非小细胞肺癌（NSCLC）患者的安全性/疗效。
设计、地点和参与者：这是一项 1 期-1b/2 期、开放标签、多中心、多国研究，纳入了晚期/转移性黑色素瘤或 NSCLC 患者，这些患者至少有 1 个可测量的病灶。
患者接受 sabatolimab 800mg 每 4 周一次加 spartalizumab 400mg 每 4 周一次，直至出现不可接受的毒性、疾病进展和/或治疗停止。
2 期主要结局测量指标为总缓解率，次要终点包括评估 sabatolimab 联合 spartalizumab 的安全性、耐受性、疗效和药代动力学。
33 名患者（黑色素瘤 n=16，NSCLC n=17）接受了 sabatolimab 加 spartalizumab 治疗。31 名（94%）患者发生了≥1 次不良事件（AE）；15 名（46%）患者发生了 3/4 级事件。NSCLC 患者最常见的≥3 级 AE 为贫血、呼吸困难和肺炎（各 n=2，12%）；黑色素瘤患者最常见的≥3 级 AE 为身体健康恶化、低钾血症、低磷血症、病理性骨折和肿瘤侵犯（各 n=1，6%）。1 名（3%）患者因 AE 停止治疗。3 名黑色素瘤患者（19%）和 6 名 NSCLC 患者（35%）出现疾病稳定。黑色素瘤和 NSCLC 患者的中位无进展生存期分别为 1.8（90%CI 1.7-1.9）和 1.7（90%CI 1.1-3.4）个月。疾病稳定的患者基线时 CD8、LAG3、程序性死亡配体 1 和抗 T 细胞免疫球蛋白和粘蛋白结构域 3 的表达水平较高。sabatolimab 的药代动力学特征与 1 期研究一致。
在接受抗程序性死亡-1/抗程序性死亡配体 1 治疗后进展的晚期/转移性黑色素瘤或 NSCLC 患者中，sabatolimab 联合 spartalizumab 耐受性良好。观察到有限的抗肿瘤活性。sabatolimab 给药的耐受性支持在各种联合治疗方案和多种肿瘤类型中探索治疗的潜力。
NCT02608268。
