Reference Detail

Ref Type

PMID

(38149055)

Authors

Li N, Li H, Wang D, Xu X

Title

Case report: SAF-189s is a potent inhibitor in a lorlatinib-resistant NSCLC patient with acquired compound mutations ALK L1196M and D1203N.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Frontiers in pharmacology	14		2023	1197163	Front Pharmacol

URL

Abstract Text

Acquired anaplastic lymphoma kinase (ALK) mutation is the major resistant mechanism to ALK tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients. At present, treatment options after acquiring secondary ALK mutations are still limited. Here, we report on a patient with metastatic ALK-rearranged NSCLC who was sequentially treated with ALK TKIs, from crizotinib to lorlatinib, and developed rare acquired compound ALK mutations (L1196M and D1203N) that confer resistance to lorlatinib. Moreover, our report describes the clinical response of an NSCLC patient with these compound mutations to multiple anti-tumor therapies. Among them, the patient was treated with SAF-189s 120 mg daily and had a stable disease lasting 3 months. Chemotherapy (pemetrexed-carboplatin) combined with bevacizumab was then administered. She achieved a partial response, which was maintained for 7 months as the best response. Since both SAF-189s and chemotherapy have shown a clear antitumor effect, they may be viable therapeutic options for these patients. Thus, our study can provide some reference in the treatment of NSCLC patients with ALK L1196M/D1203N compound mutations.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
EML4 - ALK ALK D1203N	lung adenocarcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e19:e20) who responded to Xalkori (crizotinib) treatment was found to have acquired ALK D1203N upon disease progression (PMID: 38149055).	38149055
EML4 - ALK ALK L1196M ALK D1203N	lung adenocarcinoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e19:e20) and ALK D1203N who responded to Lorbrena (lorlatinib) treatment was found to have acquired ALK L1196M upon disease progression (PMID: 38149055).	38149055
EML4 - ALK ALK D1203N	lung adenocarcinoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response and progression-free survival of 19 months in a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e19:e20) and ALK D1203N (PMID: 38149055).	38149055