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
2831 - Interleukin-6 as a Predictive Marker for Early Response to Induction Chemotherapy in Acute Myeloblastic Leukaemia
Presenter: Salah Khallaf
Session: Poster Display session 1
Resources:
Abstract
6014 - Impact of FLT3-ITD mutation on post-transplant outcome of adult AML is modified by the concomitant NPM1 mutation and pre-transplant remission status: A report from Taiwan Bone Marrow Transplant Registry (TBMTR)
Presenter: Su-peng Yeh
Session: Poster Display session 1
Resources:
Abstract
2914 - Efficacy endpoints studied in clinical trials for early-onset leukaemia
Presenter: Dylan Said
Session: Poster Display session 1
Resources:
Abstract
4691 - High triglyceride is a major risk factor of DIC and differentiation syndrome in acute promyelocytic leukemia
Presenter: Tomohiro Yamakawa
Session: Poster Display session 1
Resources:
Abstract
4395 - DREAMM 4: A Phase I/II single-arm open-label study to explore safety and clinical activity of belantamab mafodotin (GSK2857916) administered in combination with pembrolizumab in patients with relapsed/refractory multiple myeloma (RRMM)
Presenter: Suzanne Trudel
Session: Poster Display session 1
Resources:
Abstract
2808 - A Phase 1 Study of HMPL-523, a Selective Oral Anti-Spleen Tyrosine Kinase Inhibitor, in Patients with Relapsed or Refractory Lymphoma
Presenter: Nathan Fowler
Session: Poster Display session 1
Resources:
Abstract
4403 - A Phase 1 Study of HMPL-689, a Selective Oral Phosphoinositide 3-Kinase-Delta Inhibitor, in Patients with Relapsed or Refractory Lymphoma
Presenter: Jonathon Cohen
Session: Poster Display session 1
Resources:
Abstract
3357 - A global patient-driven Facebook study in a very rare sarcoma: Health-related quality of life in Epithelioid Hemangioendothelioma (EHE) patients
Presenter: Marije Weidema
Session: Poster Display session 1
Resources:
Abstract
2475 - Qualitative study of patients’ experiences of living with and beyond a soft tissue sarcoma diagnosis: the impact of sarcoma specialist services
Presenter: Ana Martins
Session: Poster Display session 1
Resources:
Abstract
2640 - Health-related quality of life issues of patients affected by desmoid-type fibromatosis; experiences from two countries
Presenter: Milea Timbergen
Session: Poster Display session 1
Resources:
Abstract