Abstract 2982
Background
Alflutinib (AST2818) is an irreversible EGFR-TKI selective for EGFR T790M mutation. We aimed to assess the safety and efficacy of alflutinib in advanced non-small cell lung cancer (NSCLC) patients with EGFR T790M mutation, who progressed after the first- or second-generation EGFR-TKI therapy.
Methods
In the phase I/II open-label, single-arm, dose-escalation and dose-expansion studies, patients with confirmed EGFR T790M mutation, locally advanced or metastatic NSCLC, who progressed after prior EGFR-TKI therapy, received alflutinib ranging from 20 - 240 mg orally once daily until disease progression or unacceptable toxicity. Patients with asymptomatic, stable central nervous system (CNS) metastases were included. The primary efficacy endpoint was the objective response rate (ORR), assessed by independent radiological review committee, in patients who received at least 1 dose with measurable disease at baseline in the dose-expansion study. Safety was assessed in all treated patients.
Results
Between Dec 27, 2016, and Oct 30, 2018, 130 (14 from dose-escalation, 116 from dose-expansion) patients received alflutinib treatment (2, 9, 48, 53, 18 patients in 20, 40, 80, 160 and 240 mg groups, respectively). By Oct 30, 2018, 79 (61%) patients remained on treatment. No dose limiting toxicity was observed. Median duration of alflutinib treatment was 226 (range: 3 - 513) days. The ORR in all treated patients was 76.7% (89/116; 95% CI: 68.0 - 84.1), duration of response ranged from 72 - 294+ days, disease control rate was 82.8% (96/116 patients). The ORR in patients with CNS metastases was 58.8% (10/17). No clear dose-response relationship was observed. Among 130 patients, 123 (95%) had treatment-related adverse events (TRAEs, including possibly not-related cases); 21 (16%) patients had grade 3 or 4 TRAEs, with the most common being decreased neutrophil count (4 patients). 20 (15%) patients had 31 serious adverse events (SAEs), 15 (12%) of them had 22 treatment-related SAEs. Five out of six deaths were due to AEs.
Conclusions
Alflutinib has promising efficacy and acceptable toxicity profile for NSCLC patients with EGFR T790M mutation who progressed after EGFR-TKI therapy. Further investigation is ongoing.
Clinical trial identification
NCT02973763, NCT03127449.
Editorial acknowledgement
Ping Liu (Linking Truth Technology Co. Ltd., China), funded by Shanghai Allist Pharmaceuticals Inc., China.
Legal entity responsible for the study
Shanghai Allist Pharmaceuticals Inc., China.
Funding
Shanghai Allist Pharmaceuticals Inc., China.
Disclosure
Y. Jiang: Full / Part-time employment: Shanghai Allist Pharmaceuticals Inc., China. All other authors have declared no conflicts of interest.
Resources from the same session
5011 - LCSCAF1 maintains cancer stem-like traits by stabilizing c-Myc protein and promotes metastasis and recurrence in lung cancer
Presenter: Tao Guo
Session: Poster Display session 1
Resources:
Abstract
4955 - XAF1 Enhances Temozolomide Induced Autophagic Cell Death through AMPK signaling pathway
Presenter: Mingoo Lee
Session: Poster Display session 1
Resources:
Abstract
5616 - The effect of cortisol on methylation patterns in breast cancer cell lines
Presenter: Haya Intabli
Session: Poster Display session 1
Resources:
Abstract
4649 - Global and sex-specific epigenome-wide association studies for the identification of the main methylated loci related to smoking in a Mediterranean population
Presenter: Judith Begona Ramirez Sabio
Session: Poster Display session 1
Resources:
Abstract
4984 - Whole transcriptomics analyses of mimicking Circulating Tumor Cells (CTCs) by single-cell RNA sequencing (scRNAseq)
Presenter: Jessica Garcia
Session: Poster Display session 1
Resources:
Abstract
5926 - Comparison of enzymatic- and bisulfite conversion to map the plasma cell-free methylome in cancer
Presenter: Nicole Lambert
Session: Poster Display session 1
Resources:
Abstract
5454 - Detection of low mutations in hepatocellular carcinoma by using circulating tumor DNA
Presenter: Esl Kim
Session: Poster Display session 1
Resources:
Abstract
4428 - Variants in the JAK1 and JAK2 genes in the risk and prognosis of patients with cutaneous melanoma
Presenter: Bruna Carvalho
Session: Poster Display session 1
Resources:
Abstract
4409 - P-Rex1 expression in breast cancer patients.
Presenter: Angela Lara Montero
Session: Poster Display session 1
Resources:
Abstract
4185 - Modulation of Risk of Cutaneous Melanoma Patients by Variants in STAT3 Gene and Functional Analysis
Presenter: Gabriela Gomez
Session: Poster Display session 1
Resources:
Abstract