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
4526 - Long-term outcome of neoadjuvant tyrosine kinase inhibitors (TKI) in locally advanced dermatofibrosarcoma protuberans (DFSP)
Presenter: Jessica Beaziz
Session: Poster Display session 1
Resources:
Abstract
1214 - Neo-adjuvant (NA) Imatinib for gastrointestinal stromal tumours (GISTs): What is the optimal length of treatment?
Presenter: Tom Wilson
Session: Poster Display session 1
Resources:
Abstract
2690 - Gastrointestinal Stromal Tumours (GIST) in adolescents and young adults (AYA)
Presenter: Nikki Ijzerman
Session: Poster Display session 1
Resources:
Abstract
4558 - Radiomics improves response evaluation for desmoid tumors treated with chemotherapy
Presenter: Amandine Crombe
Session: Poster Display session 1
Resources:
Abstract
2751 - Radiomics of gastrointestinal stromal tumors; risk classification based on computed tomography images – a pilot study
Presenter: Milea Timbergen
Session: Poster Display session 1
Resources:
Abstract
2737 - Differentiating well-differentiated liposarcomas from lipomas using a radiomics approach
Presenter: Melissa Vos
Session: Poster Display session 1
Resources:
Abstract
1282 - The immune landscape of chondrosarcoma reveals an anti inflammatory environment
Presenter: Iseulys Richert
Session: Poster Display session 1
Resources:
Abstract
1572 - Impact of Immunotherapy and Targeted Therapy on Tumor Growth Rate in Sarcoma
Presenter: Esmail Al-ezzi
Session: Poster Display session 1
Resources:
Abstract
3414 - DNA methylation profiles of angiosarcoma subtypes.
Presenter: Marije Weidema
Session: Poster Display session 1
Resources:
Abstract
3411 - Prognostic significance of circulating PD-1, PD-L1, pan-BTN3As and BTN3A1 in patients with metastatic gastrointestinal stromal tumors (mGISTs)
Presenter: Daniele Fanale
Session: Poster Display session 1
Resources:
Abstract