Ensacove (ensartinib)

We report the case of a 50-year-old woman with advanced ALK-positive NSCLC who experienced rapid tumor regression after 1 month of treatment with ensartinib, complicated by mild bilateral interstitial pneumonitis...Following progression on second-line chemotherapy, she was rechallenged with lorlatinib, which induced severe cutaneous toxicity that responded to corticosteroids...These findings highlight the need for heightened vigilance, multidisciplinary management, and the development of predictive biomarkers for TKI-associated toxicities. Future prospective studies are essential to guide safe rechallenge strategies and personalize toxicity monitoring in ALK-positive NSCLC.

P2, N=10, Terminated, National Cancer Institute (NCI) | Trial completion date: Mar 2027 --> Mar 2026 | Active, not recruiting --> Terminated; Inadequate accrual rate

The HEATR5B-ALK fusion is targetable by ensartinib, producing durable disease control and excellent tolerability. Comprehensive NGS and ALK IHC are essential for detecting rare actionable ALK variants.

P1/2, N=20, Recruiting, Tang-Du Hospital | Not yet recruiting --> Recruiting

The patient recovered well and was discharged after four postoperative days. During more than four years of follow-up, long-term ensartinib therapy was associated with stable disease without recurrence, offering potential clinical insights for managing LUAD with rare ALK variants.

The progression-free survival (PFS) exceeded 32 months, with no significant treatment-related adverse events observed. This study investigates the feasibility of combining targeted therapy with local radiotherapy, guided by genetic testing, to offer novel treatment strategies for patients with advanced primary pulmonary EIMS..

P1/2, N=164, Recruiting, Betta Pharmaceuticals Co., Ltd.

P2, N=10, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026

Among patients who received next-generation ALK TKIs as first-line therapy, continuation of next-generation ALK TKI with PT/Pem led to longer PFS and OS than PT/Pem alone, with no unanticipated toxicities. The modest efficacy of PT/Pem-based regimens overall underscores the need for more effective therapies for TKI-refractory ALK+ NSCLC.

Since the approval of crizotinib, several next-generation ALK inhibitors have been introduced, offering improved treatment outcomes. The phase III eXalt3 study, a global randomized open-label trial, compared the efficacy of ensartinib, a second-generation ALK inhibitor, with crizotinib in patients with advanced ALK-rearranged NSCLC who had not received prior ALK-targeted therapy. With superior systemic and intracranial efficacy, ensartinib stands as a promising option in precision oncology. Ongoing research into improved ALK inhibitors and novel therapeutic strategies, including immune-based approaches, is expected to further improve patient outcomes.

Among the three paradigms, MET-specific monitoring provided the most favorable diagnostic performance to identify long-term responders, with a specificity of 90% and a positive predictive value of 80%. These data demonstrate that early MET-specific ctDNA clearance is a robust on-treatment biomarker for ensartinib benefit in METex14 NSCLC, while broader ctDNA profiling remains valuable for uncovering emerging resistance mechanisms.