PMID- 35274722
OWN - NLM
STAT- MEDLINE
DCOM- 20220420
LR  - 20220420
IS  - 1549-490X (Electronic)
IS  - 1083-7159 (Print)
IS  - 1083-7159 (Linking)
VI  - 27
IP  - 3
DP  - 2022 Mar 11
TI  - Phase I Trial of a Third Generation EGFR Mutant-Selective Inhibitor (D-0316) in 
      Patients with Advanced Non-Small Cell Lung Cancer.
PG  - 163-e213
LID - 10.1093/oncolo/oyab007 [doi]
AB  - BACKGROUND: D-0316 is a third-generation epidermal growth factor receptor (EGFR) 
      tyrosine kinase inhibitor (TKI) developed for patients with locally advanced or 
      metastatic non-small cell lung cancer (NSCLC) with EGFR T790M mutation that 
      progressed after prior treatment with the first- or second-generation EGFR-TKI. 
      METHODS: This phase I, open-label, multicenter clinical trial evaluated daily 
      oral D-0316 administration in dose-escalation (25 to 150 mg; 17 patients) and 
      dose-expansion (50, 100 mg; 67 patients) cohorts for safety, tolerability, 
      anti-tumor activity, and pharmacokinetics. RESULTS: D-0316 was well tolerated at 
      daily doses of 25 to 150 mg and the maximum tolerated dose (MTD) was not reached. 
      The most common treatment-related adverse events (AEs) were platelet count 
      decreased, electrocardiogram QT corrected interval prolonged, anemia, rash, low 
      white blood cell count, hypertriglyceridemia, high cholesterol, headache, 
      pruritus, cough, and aspartate transaminase (AST) or alanine transaminase (ALT) 
      increased. Most of AEs were grade 1 or 2. In the 50 and 100 mg group, the overall 
      response rate (ORR) was 33.3% and 45.5%, the disease control rate (DCR) was 86.7% 
      and 93.9%, and the median PFS was 8.3 and 9.6 months, respectively. D-0316 
      exposure increased in proportion to dose from 25 to 150 mg. The recommended phase 
      II dose (RP2D) was 100 mg. CONCLUSION: D-0316 is safe, tolerable, and effective 
      for patients with locally advanced/metastatic NSCLC with the EGFR T790M mutation 
      who previously received EGFR-TKI. CLINICALTRIALS.GOV IDENTIFIER: NCT03452150.
CI  - (c) The Author(s) 2022. Published by Oxford University Press. The data published 
      online to support this summary are the property of the authors. Please contact 
      the authors about reuse rights of the original data.
FAU - Jian, Hong
AU  - Jian H
AD  - Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong 
      University, Shanghai, People's Republic of China.
FAU - Wang, Kai
AU  - Wang K
AD  - The Second Affiliated Hospital of Zhejiang University School of Medicine, 
      Hangzhou, People's Republic of China.
FAU - Cheng, Ying
AU  - Cheng Y
AD  - Jilin Cancer Hospital, Changchun, People's Republic of China.
FAU - Ding, Lieming
AU  - Ding L
AD  - Betta Pharmaceuticals Co., Ltd, Hangzhou, People's Republic of China.
FAU - Wang, Yang
AU  - Wang Y
AD  - Betta Pharmaceuticals Co., Ltd, Hangzhou, People's Republic of China.
FAU - Shi, Zhe
AU  - Shi Z
AD  - InventisBio Co., Ltd, Shanghai, People's Republic of China.
FAU - Zhang, Ling
AU  - Zhang L
AD  - InventisBio Co., Ltd, Shanghai, People's Republic of China.
FAU - Wang, Yaolin
AU  - Wang Y
AD  - InventisBio Co., Ltd, Shanghai, People's Republic of China.
FAU - Lu, Shun
AU  - Lu S
AD  - Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong 
      University, Shanghai, People's Republic of China.
LA  - eng
SI  - ClinicalTrials.gov/NCT03452150
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PL  - England
TA  - Oncologist
JT  - The oncologist
JID - 9607837
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - *Antineoplastic Agents/therapeutic use
MH  - *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/pathology
MH  - ErbB Receptors
MH  - Humans
MH  - *Lung Neoplasms/drug therapy/genetics/pathology
MH  - Mutation
MH  - Protein Kinase Inhibitors/adverse effects
PMC - PMC8914503
OTO - NOTNLM
OT  - EGFR T790M mutation
OT  - efficacy
OT  - epidermal growth factor receptor
OT  - non-small cell lung cancer (NSCLC)
OT  - phase I
OT  - safety
EDAT- 2022/03/12 06:00
MHDA- 2022/04/21 06:00
PMCR- 2022/02/26
CRDT- 2022/03/11 08:47
PHST- 2021/06/21 00:00 [received]
PHST- 2021/09/17 00:00 [accepted]
PHST- 2022/03/11 08:47 [entrez]
PHST- 2022/03/12 06:00 [pubmed]
PHST- 2022/04/21 06:00 [medline]
PHST- 2022/02/26 00:00 [pmc-release]
AID - 6537473 [pii]
AID - oyab007 [pii]
AID - 10.1093/oncolo/oyab007 [doi]
PST - ppublish
SO  - Oncologist. 2022 Mar 11;27(3):163-e213. doi: 10.1093/oncolo/oyab007.