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Therapy Name Lorlatinib
Synonyms
Therapy Description

Lorbrena (lorlatinib) is a small molecule inhibitor of Alk and Ros1 fusion proteins, which may result in suppression of Alk and Ros1-mediated signaling thereby inhibiting cell growth and causing tumor regression (PMID: 26144315). Lorbrena (lorlatinib) is FDA approved for use in patients with ALK-positive non-small cell lung cancer (FDA.gov).

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Drug Name Trade Name Synonyms Drug Classes Drug Description
Lorlatinib Lorbrena PF-06463922 ALK Inhibitor 22 ROS1 Inhibitor 14 Lorbrena (lorlatinib) is a small molecule inhibitor of Alk and Ros1 fusion proteins, which may result in suppression of Alk and Ros1-mediated signaling thereby inhibiting cell growth and causing tumor regression (PMID: 26144315). Lorbrena (lorlatinib) is FDA approved for use in patients with ALK-positive non-small cell lung cancer (FDA.gov).

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  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
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  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
EML4 - ALK ALK F1174L ALK G1202R Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK F1174L and ALK G1202R compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) in culture (PMID: 31585938). 31585938
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A demonstrated resistance to Lorbrena (lorlatinib) treatment in culture (PMID: 31943796). 31943796
NPM1 - ALK ALK E1210K Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK E1210K were resistant to Lorlatinib (PF-06463922) in culture (PMID: 25749034). 25749034
ALK rearrange ALK D1203N lung non-small cell carcinoma predicted - resistant Lorlatinib Clinical Study - Cohort Actionable In a retrospective study, ALK D1203N was identified in 24% (7/29) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Lorbrena (lorlatinib) treatment (PMID: 31358542). 31358542
EML4 - ALK ALK G1269A lung non-small cell carcinoma sensitive Lorlatinib Preclinical - Patient cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and growth of non-small cell lung cancer (NSCLC) cells over expressing ALK G1269A in the context of EML4-ALK in culture and in cell line xenograft models, as well as inhibited growth of patient derived NSCLC cells harboring EML4-ALK ALK G1269A in culture (PMID: 26144315). 26144315
EML4 - ALK ALK G1202R Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202R demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
ALK F1245C neuroblastoma sensitive Lorlatinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of neuroblastoma cells over expressing ALK F1245C in culture, and induced rapid and sustained complete tumor regression in patient-derived xenograft models harboring ALK F1245C (PMID: 26554404). 26554404
ALK amp neuroblastoma sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of ALK amplified neuroblastoma cells in culture (PMID: 26554404). 26554404
NPM1 - ALK ALK I1171N Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171N were resistant to Lorlatinib (PF-06463922) in culture (PMID: 25749034). 25749034
ALK L1196M ALK D1203N ALK rearrange lung adenocarcinoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, a patient with lung adenocarcinoma harboring ALK rearrangement and acquired ALK L1196M, ALK D1203N mutations demonstrated primary resistance to Lorbrena (lorlatinib) treatment, resulted in immediate disease progression (PMID: 31585938). 31585938
ALK rearrange ALK G1202R ALK L1196M lung non-small cell carcinoma resistant Lorlatinib Case Reports/Case Series Actionable In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK G1202R ALK L1196M developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
ALK rearrange ALK G1202R ALK G1269A ALK L1204V lung non-small cell carcinoma resistant Lorlatinib Case Reports/Case Series Actionable In a clinical study, ALK G1269A and L1204V were identified as acquired mutations in an ALK-positive non-small cell lung cancer patient harboring ALK G1202R who developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
EML4 - ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
ROS1 rearrange lung non-small cell carcinoma sensitive Lorlatinib Guideline Actionable Lorbrena (lorlatinib) is included in guidelines as subsequent therapy in patients with advanced or metastatic ROS1-rearranged non-small lung cancer who have progressed on Xalkori (crizotinib) or Zykadia (ceritinib) (NCCN.org). detail...
ROS1 rearrange lung non-small cell carcinoma sensitive Lorlatinib Phase I Actionable In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in an objective response in 50% (6/12) of patients with non-small cell lung carcinoma harboring a ROS1 rearrangement (PMID: 29074098; NCT03052608). 29074098
ROS1 rearrange lung non-small cell carcinoma sensitive Lorlatinib Phase Ib/II Actionable In a Phase I/II trial, Lorbrena (lorlatinib) treatment resulted in an objective response rate of 62% (13/21) in tyrosine kinase inhibitor (TKI)-naive and 35% (14/40) in previous Xalkori (crizotinib)-treated patients with non-small cell lung cancer harboring ROS1 rearrangements, intracranial responses were observed in 64% (7/11) of TKI-naive patients and 50% (12/24) of previous Xalkori (crizotinib)-treated patients (PMID: 31669155; NCT01970865). 31669155
EML4 - ALK ALK I1171N ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1171N was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
ALK rearrange ALK F1174L ALK G1202R lung non-small cell carcinoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, a patient with ALK-rearranged non-small cell lung cancer progressed on treatment with Lorbrena (lorlatinib) and subsequent testing of the tumor biopsy revealed ALK G1202R and ALK F1174L whereas testing of single isolated circulating tumor cells (CTC) revealed ALK G1202R and ALK F1174C in one CTC sample and ALK G1202R and ALK T1151M in the second CTC sample (PMID: 31439588). 31439588
ALK F1174L neuroblastoma conflicting Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, neuroblastoma cells harboring ALK F1174L were resistant to Lorbrena (lorlatinib) in culture (PMID: 30322862). 30322862
ALK F1174L neuroblastoma conflicting Lorlatinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited growth of neuroblastoma cells over expressing ALK F1174L in culture, and induced rapid and sustained complete tumor regression in both patient-derived and cell line xenograft models harboring ALK F1174L (PMID: 26554404). 26554404
EML4 - ALK ALK T1151M ALK C1156Y ALK F1174L ALK G1202R ALK S1206F ALK G1269A lung adenocarcinoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in disease progression after 3.7 months therapy in a patient with lung adenocarcinoma harboring EML4-ALK and ALK G1202R, at disease progression, ALK F1174L in cis wth ALK G1202R was identified in biopsies, and ALK C1156Y, G1269A, S1206F, and T1151M were identified in ctDNA (PMID: 31585938). 31585938
ALK rearrange ALK C1156Y ALK L1198F lung non-small cell carcinoma resistant Lorlatinib Case Reports/Case Series Actionable In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK C1156Y ALK L1198F developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
EML4 - ALK ALK I1171T Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171T demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK L1196M Advanced Solid Tumor conflicting Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M were resistant to growth inhibition mediated by Lorbrena (lorlatinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1196M Advanced Solid Tumor conflicting Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated sensitivity to Lorbrena (lorlatinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK C1156Y ALK L1256F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1256F was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK G1202R in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
ALK rearrange ALK I1171N ALK L1198F lung non-small cell carcinoma resistant Lorlatinib Case Reports/Case Series Actionable In a clinical study, a non-small cell lung cancer patient harboring ALK I1171N and L1198F in cis in the context of EML4-ALK demonstrated primary resistance to Lorlatinib (PF-06463922) (PMID: 29650534). 29650534
ALK rearrange ALK I1171X lung non-small cell carcinoma predicted - resistant Lorlatinib Clinical Study - Cohort Actionable In a retrospective study, ALK I1171X was identified in 14% (4/29) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Lorbrena (lorlatinib) treatment (PMID: 31358542). 31358542
EML4 - ALK ALK F1174C Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of transformed cells expressing EML4-ALK with ALK F1174C in culture (PMID: 26698910). 26698910
ALK rearrange ALK L1196M lung non-small cell carcinoma predicted - resistant Lorlatinib Clinical Study - Cohort Actionable In a retrospective study, ALK L1196M was identified in 38% (11/29) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Lorbrena (lorlatinib) treatment (PMID: 31358542). 31358542
ALK fusion ALK G1202R lung non-small cell carcinoma sensitive Lorlatinib Phase I Actionable In a Phase I trial, treatment with Lorlatinib (PF-06463922) demonstrated safety and resulted in durable responses in patients with ALK-positive non-small cell lung cancer, including patients harboring ALK G1202R (J Clin Oncol 34, 2016 (suppl; abstr 9009)). detail...
EML4 - ALK ALK F1174C ALK L1198F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1196M ALK L1256F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1256F was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK V1180L lung non-small cell carcinoma sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation, reduced proliferation, and induced apoptosis of non-small cell lung carcinoma cells harboring ALK V1180L in the context of EML4-ALK in culture (PMID: 26144315). 26144315
EML4 - ALK ALK F1174C ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK G1269A was identified as a compound mutation in transformed cells expressing ALK F1174C in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
ALK rearrange ALK F1174L lung non-small cell carcinoma predicted - resistant Lorlatinib Clinical Study - Cohort Actionable In a retrospective study, ALK F1174C/L was identified in 14% (4/29) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Lorbrena (lorlatinib) treatment (PMID: 31358542). 31358542
NPM1 - ALK ALK N1178H Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK N1178H were resistant to Lorlatinib (PF-06463922) in culture (PMID: 25749034). 25749034
EML4 - ALK ALK L1152R Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and cell proliferation of transformed cells over expressing ALK L1152R in the context of EML4-ALK in culture (PMID: 26144315). 26144315
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1196M and ALK D1203N compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) in culture (PMID: 31585938). 31585938
EML4 - ALK ALK F1174L ALK L1196M Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174L was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK C1156Y lung non-small cell carcinoma sensitive Lorlatinib Case Reports/Case Series Actionable In a Phase I trial, a patient with EML4-ALK positive non-small cell lung cancer with a secondary Xalkori (crizotinib) resistance mutation ALK C1156Y, was treated with Lorlatinib (PF-06463922) and displayed a 41% reduction in tumor growth after 5 weeks of treatment (PMID: 26698910; NCT01970865). 26698910
ALK rearrange ALK F1174C lung non-small cell carcinoma predicted - resistant Lorlatinib Clinical Study - Cohort Actionable In a retrospective study, ALK F1174C/L was identified in 14% (4/29) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Lorbrena (lorlatinib) treatment (PMID: 31358542). 31358542
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 irapid and sustained complete tumor regression in cell line xenograft models (PMID: 26554404). 26554404
EML4 - ALK ALK C1156Y ALK D1203N Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK D1203N was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK D1203N ALK E1210K Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
ROS1 fusion lung non-small cell carcinoma sensitive Lorlatinib Phase I Actionable In a Phase I clinical trial, Lorlatinib (PF-06463922) demonstrated safety and resulted in a 50% (26/52) overall response rate in patients with ALK-positive or ROS1-positive non-small cell lung cancer, including intracranial responses in patients with CNS metastasis (J Clin Oncol 34, 2016 (suppl; abstr 9009)). detail...
EML4 - ALK neuroblastoma sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of neuroblastoma cells harboring EML4-ALK in culture (PMID: 26554404). 26554404
NPM1 - ALK ALK F1174I Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of transformed cells expressing NPM1-ALK with ALK F1174I in culture (PMID: 25749034). 25749034
ALK rearrange ALK G1202R ALK F1174C lung non-small cell carcinoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, a patient with ALK-rearranged non-small cell lung cancer progressed on treatment with Lorbrena (lorlatinib) and subsequent testing of the tumor biopsy revealed ALK G1202R and ALK F1174L whereas testing of single isolated circulating tumor cells (CTC) revealed ALK G1202R and ALK F1174C in one CTC sample and ALK G1202R and ALK T1151M in the second CTC sample (PMID: 31439588). 31439588
EML4 - ALK ALK L1198F ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK C1156Y ALK L1196M Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK I1171S ALK L1196M Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1171S was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK G1202del Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202del demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK L1196M lung non-small cell carcinoma sensitive Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and proliferation of non-small cell lung carcinoma cells over expressing ALK L1196M in the context of EML4-ALK in culture, and resulted in tumor regression in cell line xenograft models (PMID: 26144315). 26144315
EML4 - ALK ALK I1171T ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1171T was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK C1156Y ALK F1174I Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174I was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of transformed cells expressing EML4-ALK in culture (PMID: 26698910). 26698910
ALK rearrange ALK C1156Y lung adenocarcinoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, ALK C1156Y was identified in biopsies at disease progression after 16 months of Lorbrena (lorlatinib) treatment in a patient with lung adenocarcinoma harboring ALK rearrangement, cells derived from patient's tumor were resistant to Lorbrena (lorlatinib) in culture (PMID: 31585938). 31585938
EML4 - ALK ALK C1156Y ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK G1269A was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK I1171T lung non-small cell carcinoma sensitive Lorlatinib Preclinical - Patient cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and cell growth in patient derived non-small cell lung cancer cells harboring ALK I1171T in the context of EML4-ALK in culture (PMID: 26144315). 26144315
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
NPM1 - ALK Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of transformed cells expressing NPM1-ALK in culture (PMID: 25749034). 25749034
EML4 - ALK ALK L1196M ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK C1156Y ALK G1269A lung adenocarcinoma unknown Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in disease progression after 6.9 months of therapy in a patient with lung adenocarcinoma harboring EML4-ALK, ALK C1156Y and ALK G1269A were identified in biopsies at disease progression, however, cells derived from the patient-derived xenograft (PDX) model of the patient and transformed cells expressing the compound mutation demonstrated sensitivity to Lorbrena (lorlatinib) in culture (PMID: 31585938). 31585938
EML4 - ALK ALK C1156Y ALK F1174V Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174V was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK F1174C ALK D1203N Advanced Solid Tumor decreased response Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated a decreased response to treatment with Lorlatinib (PF-06463922) in culture compared to cells expressing wild-type EML4-ALK (PMID: 27432227). 27432227
EML4 - ALK ALK L1256F lung adenocarcinoma resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) did not inhibit Alk kinase activity or proliferation of lung adenocarcinoma cells expressing ALK L1256F in the context of EML4-ALK in cell culture (PMID: 30662002). 30662002
EML4 - ALK ALK G1202R lung cancer conflicting Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation, reduced proliferation, and induced apoptosis in transformed cells over expressing ALK G1202R in the context of EML4-ALK in culture and in cell line xenograft models (PMID: 26144315). 26144315
EML4 - ALK ALK G1202R lung cancer conflicting Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK C1156Y ALK F1174C Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174C was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
ALK rearrange ALK I1171N ALK D1203N lung non-small cell carcinoma resistant Lorlatinib Case Reports/Case Series Actionable In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK I1171N and D1203N developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
ALK F1174L Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited foci formation more efficiently than Xalkori (crizotinib) in transformed cells over expressing ALK F1174L in culture (PMID: 26554404). 26554404
EML4 - ALK ALK F1174C ALK L1196M Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174C was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
NPM1 - ALK ALK C1156F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK C1156F were resistant to Lorlatinib (PF-06463922) in culture (PMID: 25749034). 25749034
ALK rearrange ALK E1210K ALK D1203N ALK G1269A lung non-small cell carcinoma resistant Lorlatinib Case Reports/Case Series Actionable In a clinical study, ALK G1269A was identified as an acquired mutation in an ALK-positive non-small cell lung cancer patient harboring ALK E1210K and D1203N, who developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
EML4 - ALK ALK S1206Y Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and cell proliferation of transformed cells over expressing ALK S1206Y in the context of EML4-ALK in culture (PMID: 26144315). 26144315
NPM1 - ALK ALK I1171T Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171T were resistant to Lorlatinib (PF-06463922) in culture (PMID: 25749034). 25749034
EML4 - ALK ALK F1174V ALK L1196M Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174V was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK L1198F Advanced Solid Tumor decreased response Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with L1198F had reduced sensitivity to growth inhibition mediated by Lorlatinib (PF-06463922) in comparison to EML4-ALK wild type in culture (PMID: 26698910). 26698910
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
ALK F1245C Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited foci formation more efficiently than Xalkori (crizotinib) in transformed cells over expressing ALK F1245C in culture (PMID: 26554404). 26554404
EML4 - ALK ALK F1174L Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and cell proliferation of transformed cells over expressing ALK F1174L in the context of EML4-ALK in culture (PMID: 26144315). 26144315
EML4 - ALK ALK C1156Y ALK I1171T Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1171T was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK E1210K Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
ALK rearrange lung non-small cell carcinoma sensitive Lorlatinib Guideline Actionable Lorbrena (lorlatinib) is included in guidelines as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer that have progressed on Xalkori (crizotinib) and Alecensa (alectinib), Alunbrig (brigatinib), or Zykadia (ceritinib), or on Alecensa (alectinib), Alunbrig (brigatinib), or Zykadia (ceritinib)(NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma sensitive Lorlatinib Guideline Actionable Lorbrena (lorlatinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement who have progressed on a second-generation ALK tyrosine kinase inhibitor (PMID: 30715168, PMID: 30285222; ESMO.org). 30285222 detail... 30715168
ALK rearrange lung non-small cell carcinoma sensitive Lorlatinib FDA approved Actionable In a Phase II trial that supported FDA approval, Lorbrena (lorlatinib) treatment resulted in an objective response (OR) rate of 47% (93/198; 4 CR, 89 PR) and a median time to overall first tumor response of 1.4 months, and an objective intracranial response rate of 63% (51/81) and median time to first intracranial response of 1.4 months in ALK-positive (rearrangement or fusion) non-small cell lung cancer patients who had received at least one prior ALK inhibitor therapy (PMID: 30413378; NCT01970865). detail... 30413378
ALK rearrange lung non-small cell carcinoma sensitive Lorlatinib Phase I Actionable In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in an objective response in 46% (19/41) of patients with non-small cell lung carcinoma harboring an ALK rearrangement (PMID: 29074098; NCT03052608). 29074098
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK G1269A Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 26698910). 26698910
ALK wild-type neuroblastoma resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) did not inhibit growth of ALK wild-type neuroblastoma cells in culture (PMID: 26554404). 26554404
EML4 - ALK lung non-small cell carcinoma sensitive Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and proliferation of non-small cell lung carcinoma cells harboring EML4-ALK fusion, and reduced intracranial tumor size in cell line xenograft models (PMID: 26144315). 26144315
ALK rearrange ALK G1202R ALK G1269A lung non-small cell carcinoma resistant Lorlatinib Case Reports/Case Series Actionable In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK G1202R ALK G1269A developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
NPM1 - ALK ALK C1156F ALK D1203N Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK C1156F and ALK D1203N were resistant to Lorlatinib (PF-06463922) in culture (PMID: 25749034). 25749034
EML4 - ALK ALK I1171S Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171S demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
ALK rearrange ALK G1202R lung non-small cell carcinoma predicted - resistant Lorlatinib Clinical Study - Cohort Actionable In a retrospective study, ALK G1202R was identified in 28% (8/29) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Lorbrena (lorlatinib) treatment (PMID: 31358542). 31358542
ALK fusion lung non-small cell carcinoma sensitive Lorlatinib Phase I Actionable In a Phase I trial, Lorlatinib (PF-06463922) demonstrated safety and resulted in a 50% (26/52) overall response rate in patients with ALK-positive or ROS1-positive non-small cell lung cancer, including intracranial responses in patients with CNS metastasis (J Clin Oncol 34, 2016 (suppl; abstr 9009)). detail...
ALK fusion lung non-small cell carcinoma sensitive Lorlatinib FDA approved Actionable In a Phase II trial that supported FDA approval, Lorbrena (lorlatinib) treatment resulted in an objective response (OR) rate of 47% (93/198; 4 CR, 89 PR) and a median time to overall first tumor response of 1.4 months, and an objective intracranial response rate of 63% (51/81) and median time to first intracranial response of 1.4 months in ALK-positive (rearrangement or fusion) non-small cell lung cancer patients who had received at least one prior ALK inhibitor therapy (PMID: 30413378; NCT01970865). detail... 30413378
ALK R1275Q Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited foci formation more efficiently than Xalkori (crizotinib) in transformed cells over expressing ALK R1275Q in culture (PMID: 26554404). 26554404
EML4 - ALK ALK I1171N Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK C1156Y ALK L1198F lung non-small cell carcinoma resistant Lorlatinib Case Reports/Case Series Actionable In a Phase I trial, a patient with EML4-ALK positive non-small lung cancer with a secondary Xalkori (critzotinib) resistance mutation C1156Y, responded to Lorlatinib (PF-06463922) but subsequently developed resistance upon the emergence of a second ALK mutation, L1198F (PMID: 26698910; NCT01970865). 26698910
EML4 - ALK ALK C1156Y Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth and ALK phosphorylation of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 26698910). 26698910
ALK rearrange ALK G1202R ALK T1151M lung non-small cell carcinoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, a patient with ALK-rearranged non-small cell lung cancer progressed on treatment with Lorbrena (lorlatinib) and subsequent testing of the tumor biopsy revealed ALK G1202R and ALK F1174L whereas testing of single isolated circulating tumor cells (CTC) revealed ALK G1202R and ALK F1174C in one CTC sample and ALK G1202R and ALK T1151M in the second CTC sample (PMID: 31439588). 31439588
EML4 - ALK ALK I1179V ALK L1196M Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1179V was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
NPM1 - ALK ALK G1128S Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK G1128S were resistant to Lorlatinib (PF-06463922) in culture (PMID: 25749034). 25749034

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Clinical Trial Phase Therapies Title Recruitment Status
NCT03726333 Phase I Lorlatinib Hepatic Impairment Study for Lorlatinib in Cancer Patients Recruiting
NCT03737994 Phase II Cisplatin + Lorlatinib Carboplatin + Lorlatinib Ceritinib Alectinib + Cisplatin Alectinib + Carboplatin Ceritinib + Cisplatin Pemetrexed Carboplatin + Ceritinib Cisplatin + Ensartinib Carboplatin + Ensartinib Brigatinib + Cisplatin Brigatinib Alectinib Brigatinib + Carboplatin Ensartinib Cisplatin + Pemetrexed Crizotinib Carboplatin + Pemetrexed Lorlatinib Biomarker/ALK Inhibitor Combinations in Treating Patients With Stage IV ALK Positive Non-Small Cell Lung Cancer (The NCI-NRG ALK Master Protocol) Recruiting
NCT02927340 Phase II Lorlatinib A Study of Lorlatinib in Advanced ALK and ROS1 Rearranged Lung Cancer With CNS Metastasis in the Absence of Measurable Extracranial Lesions Recruiting
NCT03107988 Phase I Cyclophosphamide + Lorlatinib + Topotecan Lorlatinib Study of Lorlatinib (PF-06463922) Recruiting
NCT03052608 Phase III Lorlatinib Crizotinib A Study Of Lorlatinib Versus Crizotinib In First Line Treatment Of Patients With ALK-Positive NSCLC Recruiting
NCT01970865 Phase II Lorlatinib Crizotinib A Study Of PF-06463922 An ALK/ROS1 Inhibitor In Patients With Advanced Non Small Cell Lung Cancer With Specific Molecular Alterations Active, not recruiting
NCT02584634 Phase I Crizotinib Avelumab Lorlatinib Study to Evaluate Safety, Efficacy, Pharmacokinetics And Pharmacodynamics Of Avelumab In Combination With Either Crizotinib Or PF-06463922 In Patients With NSCLC. (Javelin Lung 101) Active, not recruiting
NCT03178071 Expanded access Lorlatinib Expanded Access For Lorlatinib For Patients With Non Small Cell Lung Cancer Harboring Specific Molecular Alterations No longer available


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