Telisotuzumab Vedotin (Teliso-V) Monotherapy in Patients With Previously Treated c-MET++ Advanced Non-Small Cell Lung Cancer

Introduction

Teliso-V is an anti-c-Met antibody conjugated with a tubulin inhibitor MMAE. The aim of this phase 2 trial (NCT03539536) is to explore safety and efficacy of teliso-V in cohorts (based on histopathology and EGFR mutation) and subgroups (based on c-Met expression) of patients with c-Met+ advanced NSCLC (stage 1), followed by expansion into an appropriately selected population for further evaluation of safety and efficacy (stage 2). Abstract previously submitted to, but not yet presented at AACR 2021.

摘要：

Teliso-V是一种结合微管蛋白抑制剂MMAE的抗c- met抗体。这项2期试验(NCT03539536)的目的是研究teliso-V在c-Met+晚期NSCLC(1期)患者的队列(基于组织病理学和EGFR突变)，和亚组(基于c-Met表达)中的安全性和有效性。随后扩大到适当选择的人群，以进一步评估安全性和有效性(第二阶段)。之前提交的摘要，但尚未在2021年AACR上提出。

Methods

Patients had ECOG ≤ 1 with 1-2 prior lines of therapy including cytotoxic chemotherapy, immunotherapy and targeted therapy. c-Met status was determined centrally by IHC (SP44 antibody). Membrane staining ≥ 25% 3+ or ≥ 75% 1+ was considered positive for non-squamous and squamous, respectively. Teliso-V dose was 1.9 mg/kg Q2W. Primary endpoint was objective response rate (ORR) per central review in patients with ≥ 12 weeks follow-up. Secondary endpoints were duration of response, disease control rate, PFS and OS.

研究方法：

患者ECOG≤1，接受过1-2项治疗（包括细胞毒性化疗、免疫治疗和靶向治疗）。c-Met状态通过免疫组化(SP44抗体)集中检测。膜染色≥25% 3+或≥75% 1+，分别为非鳞状上皮阳性和鳞状上皮阳性。Teliso-V剂量为1.9 mg/kg Q2W。主要终点为随访≥12周的患者每项中心评价的客观缓解率(ORR)。次要终点为缓解时间、疾病控制率、无进展生存期和总生存期。

Results

ORR was 35.1% in the non-squamous EGFR WT cohort (53.8% in c-Met high group and 25.0% in c-Met intermediate group; Table),but was modest in the squamous and EGFR Mu cohorts. G3 or higher AEs occurred in 50/113 (44%) patients, with most common (≥ 2%) being malignant neoplasm progression (6.2%), pneumonia (5.3%), hyponatremia (4.4%), anemia (2.7%), dyspnea (2.7%), fatigue (2.7%), increased GGT (2.7%), peripheral sensory neuropathy (2.7%), and pneumonitis (2.7%). G5 AEs investigators considered possibly related to teliso-V were sudden death, dyspnea, and pneumonitis (1 event each).

结果：

在非鳞癌表皮生长因子受体（EGFR） WT队列中，ORR为35.1% (c-Met高组为53.8%，c-Met中间组为25.0%；表)，但在鳞状细胞和表皮生长因子受体（EGFR） Mu组中，ORR是适度的。50/113例(44%)患者出现G3或更高不良事件（AEs），最常见(≥2%)包括：恶性肿瘤进展(6.2%)、肺炎(5.3%)、低钠血症(4.4%)、贫血(2.7%)、呼吸困难(2.7%)、疲劳(2.7%)、GGT增加(2.7%)、周围感觉神经病变(2.7%)和肺炎(2.7%)。研究人员认为与teliso-V可能相关的G5不良事件（AEs）包括：猝死、呼吸困难和肺炎(各1例)。

Conclusion

ORR in non-squamous EGFR WT NSCLC was encouraging with a tolerable safety profile, and this cohort met prespecified criteria to transition to stage 2. In this cohort, ORR was highest in the c-Met high group, though also clinically meaningful in the intermediate group. Enrollment into the squamous cohort was stopped. Enrollment into the EGFR MU cohort will continue until the next interim analysis.

结论：

非鳞癌EGFR WT NSCLC的ORR令人鼓舞，具有可耐受的安全性，该队列符合预先规定的过渡到2期的标准。在这个队列中，ORR在c-Met高组最高，但在中间组也有临床意义。鳞状细胞队列的登记目前已停止。EGFR MU队列的登记将持续到下一次中期分析。

Table