The indication is for patients with locally advanced or metastatic disease who have not previously received treatment with an ALK-inhibitor.
Trial Name: eXalt3: Study Comparing X-396 (Ensartinib) to Crizotinib in ALK Positive Non-Small Cell Lung Cancer (NSCLC) Patients
ClinicalTrials.gov ID: NCT02767804
Sponsor: Xcovery Holdings, Inc.
Completion Date (Estimated): December 31, 2025
The FDA approved ensartinib (Ensacove; Xcovery Holdings Inc) for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non–small cell lung cancer (NSCLC) who have previously received treatment with an ALK-inhibitor. The approval comes after results from the phase 3 eXALT3 trial (NCT02767804).1,2
Ensartinib is an oral tyrosine kinase inhibitor of ALK, and when administered, it binds to and inhibits ALK kinase, ALK function proteins, and ALK point mutation variants. The current recommended dose is 225 mg orally once per day—with or without food—until disease progression or unacceptable toxicity.3,4
eXALT3 (NCT02767804) is an open-label, randomized, active-controlled, multicenter phase 3 trial that evaluated the efficacy and safety of ensartinib compared with crizotinib (Xalkori; Pfizer). A total of 290 patients (mean age: 54 years [range, 25-90 years]) with locally advanced or metastatic ALK-positive NSCLC who had not previously been treated with an ALK-targeted therapy were enrolled. Patients were randomly assigned to receive either 225 mg of ensartinib or 250 mg of crizotinib twice per day, both of which were administered with or without food until disease progression or unacceptable toxicity.1,2,4
The main efficacy outcome was progression-free survival (PFS), which was evaluated by a blinded independent central review at the 36-month point. Secondary outcome measures include overall survival (OS) which was assessed at 48 months, as well as time to central nervous system (CNS) progression and overall response rate (ORR), both of which were assessed at 36 months. Further, efficacy was evaluated in the intent-to-treat (ITT) population as well as a prespecified modified ITT (mITT) population.1,2,4
According to the results, the median PFS in the ITT population was significantly longer in patients who were treated with ensartinib (25.8 months; range, 0.03-44.0 months) compared with crizotinib (12.7 months; range, 0.03-38.6 months; HR, 0.51 [95% CI, 0.35-0.72]; P < .001). Additionally, patients receiving ensartinb had a longer median follow-up (23.8 months; range, 0-44 months) compared with crizotinib (20.2 months; range, 0-38 months).4
Further, in the mITT population, the median PFS in the ensartinib group was not reached, and the median PFS for those receiving crizotinib was about 12.7 months (95% CI, 8.9-16.6 months; HR, 0.45; 95% CI, 0.30-0.66; P < .001). Additionally, the intracranial response rate was approximately 63.6% with ensartinib compared with 21.2% in crizotinib for patients with targeted brain metastases at baseline. PFS for patients without brain metastases was not reached with ensartinib compared with 16.6 months with crizotinib as a result of a lower CNS progression rate (12-month PFS: 4.2% with ensartinib vs 23.9% with crizotinib; HR, 0.32; 95% CI, 0.16-0.63; P = .001).4
According to the FDA, the most common adverse events (AEs) reported by those receiving ensartinib were rash, musculoskeletal pain, constipation, cough, pruritic, nausea, edema, pyrexia, and fatigue.1 In the trial, AEs were similar between the ensartinib and crizotinib groups, with approximately 7.7% (n = 11) and 6.1% (n = 9) patients experiencing treatment-related serious AEs, 23.8% (n =34) and 19.9% (n = 29) experiencing dose reductions, and 9.1% (n = 13) and 6.8% (n = 10) dose discontinuations. There were no new safety signals observed during the trial.4
