PMID- 33972742
OWN - NLM
STAT- MEDLINE
DCOM- 20211210
LR  - 20221207
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 125
IP  - 2
DP  - 2021 Jul
TI  - Randomised Phase 1b/2 trial of tepotinib vs sorafenib in Asian patients with 
      advanced hepatocellular carcinoma with MET overexpression.
PG  - 200-208
LID - 10.1038/s41416-021-01380-3 [doi]
AB  - BACKGROUND: This open-label, Phase 1b/2 study evaluated the highly selective MET 
      inhibitor tepotinib in systemic anticancer treatment (SACT)-naive Asian patients 
      with advanced hepatocellular carcinoma (aHCC) with MET overexpression. METHODS: 
      In Phase 2b, tepotinib was orally administered once daily (300, 500 or 1,000 mg) 
      to Asian adults with aHCC. The primary endpoints were dose-limiting toxicities 
      (DLTs) and adverse events (AEs). Phase 2 randomised SACT-naive Asian adults with 
      aHCC with MET overexpression to tepotinib (recommended Phase 2 dose [RP2D]) or 
      sorafenib 400 mg twice daily. The primary endpoint was independently assessed 
      time to progression (TTP). RESULTS: In Phase 1b (n = 27), no DLTs occurred; the 
      RP2D was 500 mg. In Phase 2 (n = 90, 45 patients per arm), the primary endpoint 
      was met: independently assessed TTP was significantly longer with tepotinib 
      versus sorafenib (median 2.9 versus 1.4 months, HR = 0.42, 90% confidence 
      interval: 0.26-0.70, P = 0.0043). Progression-free survival and objective 
      response also favoured tepotinib. Treatment-related Grade >/=3 AE rates were 28.9% 
      with tepotinib and 45.5% with sorafenib. CONCLUSIONS: Tepotinib improved TTP 
      versus sorafenib and was generally well tolerated in SACT-naive Asian patients 
      with aHCC with MET overexpression. TRIAL REGISTRATION: ClinicalTrials.gov 
      NCT01988493.
CI  - (c) 2021. The Author(s).
FAU - Ryoo, Baek-Yeol
AU  - Ryoo BY
AUID- ORCID: 0000-0002-9052-833X
AD  - Department of Oncology, Asan Medical Center, University of Ulsan College of 
      Medicine, Seoul, Republic of Korea. ryooby@amc.seoul.kr.
FAU - Cheng, Ann-Li
AU  - Cheng AL
AUID- ORCID: 0000-0002-9152-6512
AD  - Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
FAU - Ren, Zhenggang
AU  - Ren Z
AD  - Liver Cancer Institute, Department of Hepatic Oncology, Zhongshan Hospital, Fudan 
      University, Shanghai, China.
FAU - Kim, Tae-You
AU  - Kim TY
AD  - Department of Internal Medicine, Seoul National University Hospital, Seoul, 
      Republic of Korea.
FAU - Pan, Hongming
AU  - Pan H
AD  - School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 
      China.
FAU - Rau, Kun-Ming
AU  - Rau KM
AD  - Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and E-Da 
      Cancer Hospital, Kaohsiung, Taiwan.
FAU - Choi, Hye Jin
AU  - Choi HJ
AUID- ORCID: 0000-0001-5917-1400
AD  - Department of Internal Medicine, Yonsei University College of Medicine, Seoul, 
      Republic of Korea.
FAU - Park, Joong-Won
AU  - Park JW
AD  - Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang-si, 
      Republic of Korea.
FAU - Kim, Jee Hyun
AU  - Kim JH
AD  - Department of Internal Medicine, Seoul National University Bundang Hospital, 
      Seoul National University College of Medicine, Seongnam-si, Republic of Korea.
FAU - Yen, Chia Jui
AU  - Yen CJ
AD  - Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 
      City, Taiwan.
FAU - Lim, Ho Yeong
AU  - Lim HY
AD  - Department of Medicine, Samsung Medical Center, Sungkyunkwan University, Seoul, 
      Republic of Korea.
FAU - Zhou, Dongli
AU  - Zhou D
AD  - EMD Serono Research & Development Institute, Inc. (A Business of Merck KGaA, 
      Darmstadt, Germany), Billerica, MA, USA.
FAU - Straub, Josef
AU  - Straub J
AD  - Clinical Biomarker & Companion Diagnostics, Merck KGaA, Darmstadt, Germany.
FAU - Scheele, Juergen
AU  - Scheele J
AD  - Clinical Oncology, Global Research and Development, Merck KGaA, Darmstadt, 
      Germany.
FAU - Berghoff, Karin
AU  - Berghoff K
AD  - Global Patient Safety Innovation, Merck KGaA, Darmstadt, Germany.
FAU - Qin, Shukui
AU  - Qin S
AD  - Medical Oncology Department, PLA Cancer Center, Nanjing Bayi Hospital, Nanjing, 
      China.
LA  - eng
SI  - ClinicalTrials.gov/NCT01988493
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20210510
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Piperidines)
RN  - 0 (Pyridazines)
RN  - 0 (Pyrimidines)
RN  - 1IJV77EI07 (tepotinib)
RN  - 9ZOQ3TZI87 (Sorafenib)
RN  - EC 2.7.10.1 (MET protein, human)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Asian People/genetics
MH  - Carcinoma, Hepatocellular/*drug therapy/genetics
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Liver Neoplasms/*drug therapy/genetics
MH  - Male
MH  - Middle Aged
MH  - Piperidines/*administration & dosage/adverse effects
MH  - Proto-Oncogene Proteins c-met/*genetics
MH  - Pyridazines/*administration & dosage/adverse effects
MH  - Pyrimidines/*administration & dosage/adverse effects
MH  - Sorafenib/*administration & dosage/adverse effects
MH  - Survival Analysis
MH  - Treatment Outcome
MH  - *Up-Regulation
PMC - PMC8292411
COIS- Ann-Lii Cheng has provided consulting for AstraZeneca, Bristol-Myers Squibb, 
      Eisai, Merck KGaA, Novartis, Ono Pharmaceutical, Exelixis, IPSEN Innovation, 
      Bayer Healthcare, Merck Sharp Dohme, Roche/Genentech, BeiGene, CSR Pharma Group, 
      F. Hoffmann-La Roche and IQVIA; attended speakers' bureau for Bayer Yakuhin Ltd., 
      Novartis, Eisai, Ono Pharmaceutical and Amgen Taiwan; received travel grants from 
      Bayer Yakuhin Ltd, Roche/Genentech and IQVIA. Joong-Won Park participated in 
      consultant and advisory boards for AstraZeneca, Ipsen, Bristol-Myers Squibb, 
      Roche and Bayer, and attended speaker's bureau for Bayer, Ipsen and Eisai. Ho 
      Yeong Lim attended advisory boards for Bayer, Eisai, Ono Pharmaceuticals, 
      Bristol-Myers Squibb, Merck KGaA, Ipsen, AstraZeneca, and attended speaker's 
      bureau for Bayer. Baek-Yeol Ryoo, Zhenggang Ren, Tae-You Kim, Hongming Pan, 
      Kun-Ming Rau, Hye Jin Choi, Jee Hyun Kim, Chia Jui Yen and Shukui Qin have 
      nothing to declare. Juergen Scheele was an employee of Merck KGaA, Darmstadt, 
      Germany, at the time the work was conducted. Karin Berghoff, Josef Straub and 
      Dongli Zhou are employees of Merck KGaA, Darmstadt, Germany and also hold stocks 
      with the company.
EDAT- 2021/05/12 06:00
MHDA- 2021/12/15 06:00
PMCR- 2021/05/10
CRDT- 2021/05/11 06:30
PHST- 2020/10/02 00:00 [received]
PHST- 2021/03/25 00:00 [accepted]
PHST- 2021/03/10 00:00 [revised]
PHST- 2021/05/12 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/05/11 06:30 [entrez]
PHST- 2021/05/10 00:00 [pmc-release]
AID - 10.1038/s41416-021-01380-3 [pii]
AID - 1380 [pii]
AID - 10.1038/s41416-021-01380-3 [doi]
PST - ppublish
SO  - Br J Cancer. 2021 Jul;125(2):200-208. doi: 10.1038/s41416-021-01380-3. Epub 2021 
      May 10.