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Molecular Profile ALK R1275Q
Therapy Lorlatinib
Indication/Tumor Type neuroblastoma
Response Type sensitive

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ALK R1275Q neuroblastoma sensitive Lorlatinib Case Reports/Case Series Actionable In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in a complete response in a neuroblastoma patient harboring a germline ALK R1275Q, who was on treatment for 18 months and remained in remission at 5 years (PMID: 37147298; NCT03107988). 37147298
ALK R1275Q neuroblastoma sensitive Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation, resulted in growth inhibition of neuroblastoma cells over expressing ALK R1275Q in culture and induced rapid and sustained complete tumor regression in cell line xenograft models (PMID: 26554404). 26554404
ALK R1275Q neuroblastoma sensitive Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in 3 complete responses and 1 partial response in 4 pediatric patients with relapsed or refractory neuroblastoma harboring ALK R1275Q, with treatment ongoing for an average of 52 months (PMID: 39177282). 39177282
ALK R1275Q neuroblastoma sensitive Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in 3 of 4 patients with neuroblastoma harboring ALK R1275Q (PMID: 37561984). 37561984
ALK R1275Q neuroblastoma sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) decreased viability of neuroblastoma cell lines harboring ALK R1275Q in culture (PMID: 38032104). 38032104
PubMed Id Reference Title Details
(26554404) The ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma. Full reference...
(37147298) Circulating tumor DNA reveals mechanisms of lorlatinib resistance in patients with relapsed/refractory ALK-driven neuroblastoma. Full reference...
(37561984) Anaplastic Lymphoma Kinase Inhibitors for Therapy of Neuroblastoma in Adults. Full reference...
(38032104) SHP2 inhibition with TNO155 increases efficacy and overcomes resistance of ALK inhibitors in neuroblastoma. Full reference...
(39177282) Long-Lasting Response to Lorlatinib in Patients with ALK-Driven Relapsed or Refractory Neuroblastoma Monitored with Circulating Tumor DNA Analysis. Full reference...