Efficacy, safety, and genetic analysis of furmonertinib (AST2818) in patients with EGFR T790M mutated non-small-cell lung cancer: a phase 2b, multicentre, single-arm, open-label study

Shi, Yuankai; Hu, Xingsheng; Zhang, Shucai; Lv, Dongqing; Wu, Lin; Qin, Yu; Zhang, Yiping; Liu, Li; Wang, Xiang; Cheng, Ying; Ma, Zhiyong; Huang, Niu; Wang, Dong; Feng, Jifeng; Huang, Cheng; Liu, Chunling; Zhao, Hui; Li, Jingzhang; Zhang, Xiaodong; Jiang, Yong; Gu, Chuan

doi:10.1016/s2213-2600(20)30455-0

Cited by 74 publications

(71 citation statements)

References 29 publications

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“…Third-generation EGFR-TKI almonertinib (HS-10296, NCT02981108), resulting in an objective rate (ORR) of 68•9% in patients with previously treated EGFR T790M-positive NSCLC in a phase II study, was approved by NMPA on Mar 18th, 2020, three years after osimertinib marketing in China [26] . Furmonertinib (AST2818, NCT03452592) showed an ORR of 73•6% in EGFR T790M mutated NSCLC in a phase IIb trial, and gained its approval on Mar 3rd, 2021 [27] . Additionally, gefitinib (NCT01405079), erlotinib (NCT01683175), and osimertinib (NCT02511106) improved disease-free survival in adjuvant setting in Chinese NSCLC patients with EGFR-sensitizing mutations [28] , [29] , [30] .…”

Section: Discussionmentioning

confidence: 99%

The changing landscape of anti-lung cancer drug clinical trials in mainland China from 2005 to 2020

Zhong

Tao

Chen

et al. 2021

The Lancet Regional Health - Western Pacific

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Background In recent years, new drug development on lung cancer is in full swing in China. The aim of this study was to overview the changing landscape of anti-lung cancer drug clinical trials in mainland China from 2005 to 2020. Methods We analysed anti-lung cancer drug clinical trials registered on three websites including the China National Medical Products Administration Centre for Drug Evaluation platform, the Chinese Clinical Trial Registry and ClinicalTrials.gov. Findings A total of 1595 anti-lung cancer drug clinical trials from Jan 1st, 2005 to Dec 31st, 2020 were extracted, which included 630 (39•5%) investigator-initiated trials (IITs), 698 (43•8%) domestic industry-sponsored trials (ISTs), and 267 (16•7%) international ISTs. During the past 16 years, the number of anti-lung cancer clinical trials including IITs and domestic ISTs had a remarkable growth, however, the number of international ISTs increased slowly. The number of principal clinical trial units also increased significantly over time. Of the 1595 trials, the largest growth was observed in phase I trials during 2013–2020, with an average annual growth rate of 38•6%. 278 trials were led by principal investigators (PI) from Guangdong, followed by Beijing ( n =273) and Shanghai ( n =257). Among the 965 ISTs, clinical trials involving targeted drugs (588, 60•9%) accounted for the largest proportion, followed by immunotherapeutic drugs (284, 29•4%), cytotoxic drugs (75, 7•8%), and traditional Chinese medicine (18, 1•9%). In terms of targeted drugs, EGFR-TKIs remained the most studied drugs (225/588, 38•27%). As for immunotherapy, 125 out of 284 (44•01%) trials involved PD-1 inhibitors, 60 (21•13%) trials involved PD-L1 inhibitors, and seven (2•46%) trials involved CTLA-4 inhibitors. Interpretation In the past 16 years, the development of anti-lung cancer drug clinical trials has achieved much progress in mainland China. The most progress lied in targeted therapy and immunotherapy. Funding This work was financially supported in part by China National Major Project for New Drug Innovation (2017ZX09304015) and Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1-001).

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Section: Discussionmentioning

confidence: 99%

The changing landscape of anti-lung cancer drug clinical trials in mainland China from 2005 to 2020

Zhong

Tao

Chen

et al. 2021

The Lancet Regional Health - Western Pacific

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“…The CNS mPFS among the 86 patients with measurable or nonmeasurable CNS metastasis was 11.0 months (95% CI: 8.3-NR). 28 At an early data cutoff of July 2019, the IC-ORR by IRC for rezivertinib at 180 mg daily was 32% (8 of 25) with several ongoing unconfirmed partial responses. 31…”

Section: Intracranial Orrmentioning

confidence: 98%

“…Grade 3 or higher TRAEs were elevation of ALT (1.4%), AST (1.4%), or gamma-glutamyl transferase (1.4%). 28 Alflutinib was approved in China in March 3, 2021 for treatment of EGFR T790Mþ NSCLC. A phase 3 trial FLAG comparing alflutinib with gefitinib in 1L treatment of patients with EGFRþ NSCLC is ongoing (NCT03787992) (Table 1).…”

Section: Almonertinib (Hs-10296)mentioning

confidence: 99%

Beyond Osimertinib: The Development of Third-Generation EGFR Tyrosine Kinase Inhibitors For Advanced EGFR+ NSCLC

Nagasaka

Zhu

Lim

et al. 2021

Journal of Thoracic Oncology

149

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Single-agent osimertinib is the standard of care for the firstline treatment of advancedEGFRþ NSCLC and remained the only marketed third-generation EGFR tyrosine kinase inhibitor (TKI) until March 2020 when almonertinib (HS-10296) was approved in the People's Republic of China for the treatment of advanced EGFR T790Mþ NSCLC based on a phase 2 expansion study of a phase 1/2 trial. In this review, we profiled many of the third-generation EGFR TKIs in latestage clinical development (e.g., almonertinib, lazertinib, alflutinib 1 , rezivertinib, ASK120069, SH-1028, D-0316, and abivertinib) based on their interim results from phase 1 and phase 2 trials, and included the designs of the phase 3 trials and their chemical structures when publicly available. We also listed other third-generation EGFR TKIs in pipeline development based on the search of clinical trial registration websites. In addition, we summarized the results of clinical trials that previously reported third-generation EGFR TKIs (rociletinib, olmutinib, nazartinib, mavelertinib), including phase 3 results of rociletinib and naquotinib. We further profiled combination clinical trial design of the thirdgeneration EGFR TKIs including FLAURA2 (NCT04035486), MARIPOSA (NCT04487080), ACROSS1 (NCT04500704), and ACROSS2 (NCT04500717) that if positive can potentially usher in the next standard of care for advanced EGFRþ NSCLC.

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“… 127 The ORR and PFS of patients with CNS metastasis were 66% and 11.6 months. 64 , 128 Aulmonertinib and furmonertinib are both under clinical investigation on first‐line treatment for advanced NSCLC patients harboring sensitizing EGFR mutations.…”

Section: Targeted Therapy For Nsclcmentioning

confidence: 99%

Therapeutic advances in non‐small cell lung cancer: Focus on clinical development of targeted therapy and immunotherapy

Yuan

Zhang

2021

MedComm

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Lung cancer still contributes to nearly one‐quarter cancer‐related deaths in the past decades, despite the rapid development of targeted therapy and immunotherapy in non‐small cell lung cancer (NSCLC). The development and availability of comprehensive genomic profiling make the classification of NSCLC more precise and personalized. Most treatment decisions of advanced‐stage NSCLC have been made based on the genetic features and PD‐L1 expression of patients. For the past 2 years, more than 10 therapeutic strategies have been approved as first‐line treatment for certain subgroups of NSCLC. However, some major challenges remain, including drug resistance and low rate of overall survival. Therefore, we discuss and review the therapeutic strategies of NSCLC, and focus on the development of targeted therapy and immunotherapy in advanced‐stage NSCLC. Based on the latest guidelines, we provide an updated summary on the standard treatment for NSCLC. At last, we discussed several potential therapies for NSCLC. The development of new drugs and combination therapies both provide promising therapeutic effects on NSCLC.

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Efficacy, safety, and genetic analysis of furmonertinib (AST2818) in patients with EGFR T790M mutated non-small-cell lung cancer: a phase 2b, multicentre, single-arm, open-label study

Cited by 74 publications

References 29 publications

The changing landscape of anti-lung cancer drug clinical trials in mainland China from 2005 to 2020

The changing landscape of anti-lung cancer drug clinical trials in mainland China from 2005 to 2020

Beyond Osimertinib: The Development of Third-Generation EGFR Tyrosine Kinase Inhibitors For Advanced EGFR+ NSCLC

Therapeutic advances in non‐small cell lung cancer: Focus on clinical development of targeted therapy and immunotherapy

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