医脉通编译整理，转载请务必注明出处。
2016年6月3-7日，一年一度的美国临床肿瘤学会（American Society of ClinicalOncology, ASCO）年会将在芝加哥举办。本次大会将吸引30000名全世界的肿瘤领域专家学者和参会人员，会议摘要收录了多个我国学者主导的肿瘤前沿研究。
南京解放军八一医院副院长、全军肿瘤中心主任秦叔逵教授带领的亚洲团队开展了一项开放标签的Ⅰb/Ⅱ期临床研究，Ⅰb期主要确定新型c-Met小分子抑制剂Tepotinib在晚期肝癌患者中的2期推荐剂量，评价安全性、疗效和药代动力学。Ⅱ期主要对比Tepotinib和索拉菲尼（Sorafenib）作为一线治疗c-Met阳性晚期肝癌疗效和副作用。
Tepotinib是一种新型高选择性c-Met小分子抑制剂，在前期的安全性研究中对c-Met阳性的肿瘤显示出较好的安全性和潜在的抗肿瘤活性。索拉菲尼是一种多靶点抑制剂，具有抑制肿瘤细胞增殖和血管形成的双重作用，已批准用于晚期肝癌的治疗。
摘要编号：4072
时间：6月4日，上午8:00-11:30
报告形式：壁报展示
该研究是一项3+3剂量递增研究（300mg/d，500mg/d，1000mg/d），21天为一周期。入组肝癌患者的主要要求：
◆巴塞罗那肝癌分级（BCLC）为C级
◆Met+（Ⅱ期要求）
◆Child-Pugh肝功能分级A级，无
◆ECOG PS 0-2
◆期望寿命≥3个月
研究纳入27例肝癌患者，其中7人接受300mg/d，14人接受500mg/d，6人接受1000mg/d。
结果
副反应方面，未发现剂量限制性毒性（DLT）。22名患者有治疗相关突发不良反应（Treatment-relatedtreatment-emergent adverse events, TRTEAEs），大多数≤2级，最常见的为
在治疗反应反面，c-Met阳性患者（7例）中的最佳疗效（Best overall response, BOR）是部分缓解（2）、疾病稳定（2）和疾病进展（3）。获得部分缓解的2例患者分别接受500mg/d和1000mg/d剂量，治疗过程中AFP水平保持稳定。c-Met阴性患者（18例）中6例疾病稳定，10例疾病进展、2例无法评估。
结论
研究结果提示Tepotinib在1000mg/d剂量时肝癌患者可以耐受，c-Met+患者似乎有更好的疗效。该研究Ⅱ期比较Tepotinib和索拉菲尼作为一线治疗c-Met+HCC的疗效，目前正在进行中。临床试验在clinicaltrials.gov注册号：NCT01988493。
会议专题》》》2016年ASCO年会专题报道
摘要阅读
Abstract No:4072
Tolerability and activity of tepotinib in Asian patients with advanced hepatocellular carcinoma (HCC)
Session: Gastrointestinal (Noncolorectal) Cancer
Type: Poster Session
Author(s): Shukui Qin,Ho Yeong Lim,Baek-Yeol Ryoo,et al.
Background: Patients (pts) with advanced HCC have a poor prognosis, particularly if tumor c-Met activity is aberrant. Current first-line therapy is sorafenib, which has limited efficacy and is not widely used in Asia. Tepotinib (MSC2156119J) is a highly selective c-Met inhibitor with favorable safety and promising antitumor activity, particularly in c-Met+ tumors. Translational modeling established a recommended phase II dose (RP2D) of 500 mg/day. All patients enrolled into a phase Ib trial of tepotinib in Asian pts with HCC have completed the dose-limiting toxicity (DLT) evaluation period and data are reported.
Methods: Asian adults with confirmed HCC of BCLC Stage C, Child-Pugh Class A liver function without encephalopathy, and ECOG PS 0–2 were recruited to this 3+3 dose-escalation study (tepotinib 300 or 500 mg/day, 21-day cycle; protocol amendment added a 1,000 mg/day cohort, n = 6). In total, 12 patients were to be enrolled at the RP2D. c-Met expression was retrospectively determined by IHC. PK was analyzed by non-compartmental methods.
Results: 27 pts were enrolled (median age 57 [38-69]; male 23; ECOG PS 0/1 11/15). 7 received tepotinib 300 mg/day, 14 500 mg/day, and 6 1,000 mg/day. No DLTs were observed. 22 pts experienced treatment-related treatment-emergent adverse events (TRTEAEs); most were grade ≤ 2. The most common TRTEAEs were diarrhea (n = 10), elevated AST (7), nausea (7), and elevated ALT (6). 15 grade ≥ 3 TRTEAEs occurred, including grade 3 increased lipase levels (n = 3) and grade 3 diarrhea (n = 2). Best overall response (BOR) in pts with c-Met+ (n = 7) tumors was partial response (n = 2), stable disease (SD; n = 2), and progressive disease (PD; n = 3). The 2 pts with PRs were treated with tepotinib 500 and 1,000 mg/day, respectively; AFP levels in these pts were at least stabilized during response to tepotinib. Of 18 pts with c-Met– tumors, 6 had a BOR of SD, 10 PD, and 2 were not evaluable.
Conclusions: Data indicate that tepotinib at doses of up to 1,000 mg/day is well tolerated by Asian pts with HCC. Efficacy appeared to be greatest in the c-Met+ population. The ongoing phase II part of this study is comparing the efficacy and safety of first-line tepotinib and sorafenib in pts with c-Met+ HCC. Clinical trial information: NCT01988493
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医脉通编译自：Shukui Qin,et al.Tolerability and activity of tepotinib in Asian patients with advanced hepatocellular carcinoma (HCC).J Clin Oncol 34,2016(suppl;abstr 4072).
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