Phase II trial comparing tepotinib + gefitinib with cisplatin + pemetrexed in A
PUBLISHED: 2015-11-26  884 total views, 1 today

Yilong Wu1, Keunchil Park2, Dongwan Kim3, Ross a. Soo4, Cindy Li5

Huiling Xiong5, Christian Ihling6, James chih-hsin Yang7

1Lung Cancer, Guangdong General Hospital (GGH) & Guangdong Academy of Medical Sciences, Guangzhou, China, 2Innovative Cancer Medicine Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, 3Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea, 4National University Cancer Institute, National University Health System, Singapore, 5Merck Serono Pharmaceutical R&D Co., Ltd., Beijing, China, 6Merck KGaA, Darmstadt, Germany, 7National Taiwan University, Graduate Institute of Oncology, Taipei, Taiwan

 

Background:The combination of the highly selective c-Met inhibitor tepotinib (MSC2156119J) + gefitinib was shown to be well tolerated and have antitumor activity possibly associated with c-Met-positive tumor status in the phase Ib part of this trial, which involved patients (pts) with gefitinib-resistant locally advanced/metastatic c-Met+ NSCLC. A tepotinib dose of 500mg/day was selected for use in the phase II part. The soon to be initiated phase II part of the trial (NCT01982955) is described. Trial design: Eligible pts are Asian adults with histologically or cytologically confirmed, gefitinib-resistant locally advanced/metastatic NSCLC other than predominantly squamous histology. Other inclusion criteria include: ECOG PS 0/1; activating EGFR mutations; T790M status assessed centrally using the therascreen® EGFR RGQ PCR Kit [QIAGEN]); confirmed c-Met+ tumors using immunohistochemistry (2+/3+ c-Met protein overexpression using Dako MET IHC MSC2156119J pharmDx anti-total c-MET [D1C2] rabbit MAb [Dako]). FISH (probe: Dako MET/CEN-7 IQFISH Probe Mix (IUO); c-Met: CEP7 ratio ≥2) will be used to prospectively assess c-Met amplification status. Pts with c-Met+, EGFR T790M– NSCLC (n=136) will be randomized to tepotinib 500mg/day p.o. + gefitinib 250mg/day q3w or cisplatin 75mg/m2 + pemetrexed 500mg/m2q3w for up to 6 cycles. Pts with c-Met+, T790M+ NSCLC (n=15) will receive tepotinib 500mg/day p.o. + gefitinib 250mg/day q3w. The primary objective is to determine whether progression-free survival (PFS) with second-line tepotinib + gefitinib is superior to that of pemetrexed + cisplatin in pts with c-Met+, T790M– advanced NSCLC and acquired resistance to first-line gefitinib. An interim analysis is planned when 50% of PFS events have occurred in both arms. Secondary objectives are to evaluate: tolerability; efficacy in pts with c-Met+, T790M- tumors; antitumor activity in pts with c-Met+, T790M+ tumors; and patient-reported outcome in all pts. This randomized phase II trial will provide evidence of whether tepotinib has a role in the treatment of Asian pts with c-Met+, T790M– NSCLC with activating EGFR mutations and acquired resistance to first-line gefitinib.

 

Key Words: NSCLC


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