Telisotuzumab Vedotin (Teliso-V) Monotherapy in Patients With Previously Treatedc-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是一種結合微管蛋白抑製劑MMAE的抗c- met抗體。這項2期試驗(NCT03539536)的目的是研究teliso-V在c-Met+晚期NSCLC(1期)患者的隊列(基於組織病理學和EGFR突變)，和亞組(基於c-Met表達)中的安全性和有效性。隨後擴大到適當選擇的人群，以進一步評估安全性和有效性(第二階段)。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，接受過1-2項治療（包括細胞毒性化療、免疫治療和靶向治療）。c-Met狀態通過免疫組化(SP44抗體)集中檢測。膜染色≥25% 3+或≥75% 1+，分別為非鱗狀上皮陽性和鱗狀上皮陽性。Teliso-V劑量為1.9 mg/kg Q2W。主要終點為隨訪≥12周的患者每項中心評價的客觀緩解率(ORR)。次要終點為緩解時間、疾病控製率、無進展生存期和總生存期。

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).

結果：

在非鱗癌表皮生長因子受體（EGFR） WT隊列中，ORR為35.1% (c-Met高組為53.8%，c-Met中間組為25.0%；表)，但在鱗狀細胞和表皮生長因子受體（EGFR） Mu組中，ORR是適度的。50/113例(44%)患者出現G3或更高不良事件（AEs），最常見(≥2%)包括：惡性腫瘤進展(6.2%)、肺炎(5.3%)、低鈉血症(4.4%)、貧血(2.7%)、呼吸困難(2.7%)、疲勞(2.7%)、GGT增加(2.7%)、周圍感覺神經病變(2.7%)和肺炎(2.7%)。研究人員認為與teliso-V可能相關的G5不良事件（AEs）包括：猝死、呼吸困難和肺炎(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.

結論：

非鱗癌EGFR WT NSCLC的ORR令人鼓舞，具有可耐受的安全性，該隊列符合預先規定的過渡到2期的標準。在這個隊列中，ORR在c-Met高組最高，但在中間組也有臨床意義。鱗狀細胞隊列的登記目前已停止。EGFR MU隊列的登記將持續到下一次中期分析。

Table