Safety, pharmacokinetics, and efficacy of BPI-15086 in patients with EGFR T790M-mutated advanced non-small-cell lung cancer: results from a phase I, single-arm, multicenter study.
ESMO Open
; 7(3): 100473, 2022 06.
Article
in En
| MEDLINE
| ID: mdl-35526510
ABSTRACT
BACKGROUND:
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) resistance frequently occurs in patients with non-small-cell lung cancer (NSCLC). EGFR Thr790Met mutation (T790M+) is seen in â¼50% of patients. We assessed the safety, tolerability, and pharmacokinetics (PK) of BPI-15086, a novel, ATP-competitive, irreversible, third-generation, mutation-selective EGFR-TKI in patients with EGFR T790M-mutated NSCLC. PATIENTS ANDMETHODS:
This two-center, phase I, dose-escalation study included patients who were 18-65 years old, with an Eastern Cooperative Oncology Group performance status of 0-2, with histologically or cytologically confirmed locally advanced or metastatic T790M+ NSCLC who were not surgical or radiotherapy candidates, and had imaging-identified disease progression after prior EGFR-TKIs. This dose-escalation study enrolled patients using a 3 + 3 study design. Patients received 25, 50, 100, 200, and 300 mg/day orally in 21-day cycles. The primary endpoints were safety, tolerability, and PK. Secondary endpoints were objective response rate (ORR) and disease control rate (DCR). The dose-expansion study was not conducted.RESULTS:
We enrolled 17 patients from 29 December 2016 to 16 May 2018, in the safety and full analysis sets. All patients completed a single dosing trial, and no adverse events (AEs) causing drug discontinuation were seen. Grade 1-2 nausea, hypoalbuminemia, and decreased appetite were the most common treatment-related AEs. Grade 3 hyperglycemia was seen in one patient dosed at 300 mg/day. The ORR and DCR were 17.7% [95% confidence interval (CI) 3.8% to 43.4%] and 47.1% (95% CI 23.0% to 72.2%), respectively.CONCLUSION:
BPI-15086 is a safe and tolerable third-generation EGFR-TKI with a rationale for further clinical studies.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma, Non-Small-Cell Lung
/
Lung Neoplasms
Type of study:
Clinical_trials
/
Prognostic_studies
Limits:
Adolescent
/
Adult
/
Aged
/
Humans
/
Middle aged
Language:
En
Journal:
ESMO Open
Year:
2022
Document type:
Article