Ensatinib Treat Second-generation ALK-TKI Resistance After Second-generation ALK-TKI Resistance
Status:
Recruiting
Trial end date:
2024-12-31
Target enrollment:
Participant gender:
Summary
After the use of second-generation ALK-TKI drug resistance, about 50% of tissue biopsies
showed mutations in the ALK kinase domain, and appropriate ALK-TKI could be selected
according to different mutation sites .Phase I/II clinical trials in the US of ensatinib
showed ORR of 25% (4/16) in patients previously treated with crizotinib and second-generation
ALK-TKI (N=16) .In the phase II registered clinical study in China, biomarker analysis also
showed that the ORR of ensatinib against drug resistance site G1202R was 33% (2/6).The ORR of
I1171 and F1174 were 50% (2/4) and 71% (5/7), respectively, suggesting that ensatinib may
still be effective in patients with drug resistance to other second-generation ALK inhibitors
. Investigators designed this study to evaluate the clinical efficacy of ensatinib after
second-generation ALK-TKI resistance.The study was a single-arm, multi-center Phase II
clinical study, using ORR of patients with measurable lesions as the primary endpoint, and
using Simon two-stage design to estimate the required sample size.At a 5% level of
significance and 85% confidence, a minimum of 40 evaluable subjects were required for both
phases.In the first stage, 20 patients were enrolled. If 2 patients had objective response,
an additional 20 patients were enrolled in the second stage. If more than 5 patients /40
patients had objective response, the therapeutic drugs were considered effective.Eligible
patients will take 225mg of ensaritinib orally once daily, on an empty stomach or with food,
until the patient develops disease progression, develops unacceptable toxicity, the
investigator or subject decides to drop out, loses follow-up, starts another antitumor
therapy, or dies.The primary end points were objective response rate (ORR) to disease
progression, occurrence of unacceptable toxicity, investigator or subject decision to drop
out, loss of follow-up, initiation of other antitumor therapy, or death.