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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.
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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 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
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