Ensacove (ensartinib)

P2, N=45, Not yet recruiting, Shanghai Pulmonary Hospital, Shanghai, China

This retrospective study included patients who developed CNS progression (time 0, [T0]) on alectinib, lorlatinib, brigatinib, or ensartinib. The median intracranial progression-free survival from T0 was not significantly different between the TKI-altered versus unaltered groups (p = 0.21). For patients with ALK-rearranged NSCLC with leptomeningeal progression or concurrent systemic progression, TKI change or dose increase was a feasible salvage strategy for CNS progression during treatment with CNS-penetrable TKI.

The patient received first-line chemotherapy with pemetrexed (820 mg on day 1) plus cisplatin (40 mg on days 1-3) every 21 days and achieved a remarkable progression-free survival (PFS) of 48 months...She was subsequently treated with ensartinib (225 mg once daily), yielding a favorable response...Unless there are studies with large cohorts clarifying the case, an individualized regimen-potentially starting with chemotherapy and transitioning to targeted agents-may be justified. Further clinical experience and collaborative research are essential to develop evidence-based guidelines for this exceptionally rare subset.

EST and Encorafenib (ECB as the internal standard) were differentiated using an isocratic mobile phase system on a reversed stationary phase (Eclipse Plus C18) column. In silico data proposed that minor structural modifications to the dichlorophenyl moiety or the piperazine ring during drug design may enhance the safety profile and metabolic stability relative to the properties of EST. Evaluating the EST metabolic stability and in silico ADME characteristics is essential for advancing innovative therapeutic research focused on improving metabolic stability.

Phase III trial confirmed superior PFS with ensartinib compared to crizotinib. This review received no specific funding. The protocol was not registered.

The corresponding PDO model demonstrated sensitivity to a combination of pemetrexed, carboplatin, and osimertinib, but insensitivity to osimertinib monotherapy...The patient had progressed on multiple lines of therapy, including alectinib and lorlatinib. The PDO model showed sensitivity to brigatinib but insensitivity to ensartinib. Subsequent treatment with brigatinib induced a PR that was sustained for 5.8 months; the patient survived for a total of 9 months following the initiation of this PDO-guided therapy. These two cases suggests that PDOs derived from primary and metastatic lesions may help optimize treatment regimens for patients with lung cancer brain metastases, thereby enabling personalized therapy and potentially improving survival outcomes.

This is the first report of a patient with SQSTM1-ALK fusion who experienced different responses after treatment with alectinib, ensartinib, lorlatinib, and brigatinib. We hope that this case provides clinical evidence to guide treatment strategies for this rare variant and further supports the individualized application of ALK-tyrosine kinase inhibitors (TKIs) in patients with non-classical fusions.

After multidisciplinary evaluation and considering the patient's refusal to undergo local therapies, treatment was switched to lorlatinib. The case underscores the need for continued vigilance and individualized surveillance strategies even once favorable pathological responses are achieved. Additionally, the perioperative evolution of skin toxicity highlights the importance of continuous adverse event monitoring and management.

• A PCR-based mutation prediction system was successfully applied to fourth-generation ALK inhibitors. • Neladalkib showed efficacy against G1202R-positive relapses with minimal evidence of secondary resistance mutations. • Sequential combinations of gilteritinib with either neladalkib or ensartinib may sustain efficacy and delay resistance in I1171N-positive relapses.

P2, N=27, Active, not recruiting, Fudan University | Unknown status --> Active, not recruiting | Trial completion date: Oct 2020 --> Jun 2026 | Trial primary completion date: Jul 2020 --> Jun 2025

OP should be considered when new lesions appear in the lungs of lung cancer patients, and distinguished from infectious pneumonia, metastasis, or cancer progression. In this respect, pathological biopsy plays an important role in diagnosis. In our case, discontinuation of ceritinib and regular steroid administration were effective.

We suggest that serum amylase may be a tumor marker that may lead to a more effective approach to the diagnosis and treatment of related diseases.