ALK Fusion

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Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
High-Grade Glioma, NOS1
EML4::ALK Fusion	Entrectinib	Predictive	C	Does Not Support Sensitivity Response	2	submitted	EID12607 In the STARTRK-NG Phase 1/2 trial of entrectinib in pediatric patients, with extracranial solid tumors or primary CNS tumors, aged <22 years with relapsed or refractory disease, tumors with fusions… (full text at CIViC) PMID 35395680 · Desai et al., 2022 · Open in CIViC	civic
Lung Acinar Adenocarcinoma1
EML4::ALK Fusion	Erlotinib	Predictive	C	Supports Resistance	2	accepted	EID1121 A 39-year-old man presented was observed to have lung acinar adenocarcinoma. Treatment with chemotherapy produced no remarkable response. A EGFR L858R point mutation was observed; the patient was ther… (full text at CIViC) PMID 23181703 ·

Molecular profile

Therapy

Type

Level

Direction · significance

Rating (1–5)

Status

Evidence

Source

High-Grade Glioma, NOS1

EML4::ALK Fusion

Entrectinib

Predictive

Does Not Support Sensitivity Response

submitted

EID12607

In the STARTRK-NG Phase 1/2 trial of entrectinib in pediatric patients, with extracranial solid tumors or primary CNS tumors, aged <22 years with relapsed or refractory disease, tumors with fusions… (full text at CIViC)

PMID 35395680 · Desai et al., 2022 · Open in CIViC

civic

Lung Acinar Adenocarcinoma1

EML4::ALK Fusion

Erlotinib

Predictive

Supports Resistance

accepted

EID1121

A 39-year-old man presented was observed to have lung acinar adenocarcinoma. Treatment with chemotherapy produced no remarkable response. A EGFR L858R point mutation was observed; the patient was ther… (full text at CIViC)

PMID 23181703 ·

Lung Adenocarcinoma9
EML4::ALK Fusion	Crizotinib	Predictive	C	Supports Sensitivity Response	4	accepted	EID262 A 28 year-old patient with non-small cell lung cancer that failed conventional therapy was found to harbor the EML4-ALK (E13;A20) fusion using reverse transcription PCR. Treatment with 250mg crizotini… (full text at CIViC) PMID 20979473 · Choi et al., 2010 · Open in CIViC	civic
EML4::ALK Fusion AND ABCB1 Overexpression	Alectinib + LorlatinibSubstitutes	Predictive	D	Does Not Support Resistance	3	accepted	EID10016 EML4-ALK fusion positive lung adenocarcinoma cell lines with high expression of P-gp (ABCB1 gene) (H3122 and the newly established JFCR013-2) were found to be resistant to crizotinib and ceritinib. P-… (full text at CIViC) PMID 26870817 · Katayama et al., 2016 · Open in CIViC	civic
EML4::ALK Fusion AND ABCB1 Overexpression	Ceritinib + CrizotinibSubstitutes	Predictive	D	Supports Resistance	3	accepted	EID7869 EML4-ALK fusion positive lung adenocarcinoma cell lines (H3122 and the newly established JFCR013-2) with high expression of P-gp (ABCB1 gene) were found to be resistant to crizotinib and ceritinib. P… (full text at CIViC) PMID 26870817 · Katayama et al., 2016 · Open in CIViC	civic
EML4::ALK Fusion AND ALK C1156Y	Crizotinib	Predictive	C	Supports Resistance	4	accepted	EID236 A 28 year-old patient with T4N3M1 stage lung adenocarcinoma harboring an EML4-ALK variant 1 fusion was treated with crizotinib after failing conventional therapy. The patient achieved a partial respon… (full text at CIViC) PMID 20979473 · Choi et al., 2010 · Open in CIViC	civic
EML4::ALK Fusion AND ALK C1156Y	Crizotinib	Predictive	C	Supports Resistance	2	accepted	EID4046 In a lung adenocarcinoma cancer patient with an EML4-ALK gene rearrangement (a known sensitizing alteration to crizotinib) and an ALK C1156Y co-mutation, ALK C1156Y was reported to be refractory to cr… (full text at CIViC) PMID 27045755 · Saber et al., 2016 · Open in CIViC	civic
EML4::ALK Fusion AND ALK G1269A	Crizotinib	Predictive	C	Supports Resistance	2	accepted	EID4620 In a lung adenocarcinoma cancer patient with an EML4-ALK gene rearrangement (a known sensitizing alteration to crizotinib) and an ALK G1269A co-mutation, ALK G1269A was reported to be refractory to cr… (full text at CIViC) PMID 27045755 · Saber et al., 2016 · Open in CIViC	civic
EML4::ALK Fusion AND ALK L1196M	Crizotinib	Predictive	C	Supports Resistance	4	accepted	EID237 A 28 year-old patient with non-small cell lung cancer was found to harbor the EML4-ALK (E13;A20) fusion using reverse transcription PCR. Treatment with 250mg crizotinib twice daily resulted in rapid i… (full text at CIViC) PMID 20979473 · Choi et al., 2010 · Open in CIViC	civic
EML4::ALK Fusion AND ALK L1196M	Crizotinib	Predictive	C	Supports Resistance	2	submitted	EID4040 In a stage IV Hodgkin's lymphoma patient with metastatic lung adenocarcinoma harboring an EML4-ALK gene rearrangement (a known sensitizing alteration to crizotinib) and an ALK L1196M�co-mutation, ALK … (full text at CIViC) PMID 27507192 · Zhang et al., 2017 · Open in CIViC	civic
EML4::ALK Fusion AND ALK L1196M	Crizotinib	Predictive	D	Supports Resistance	2	submitted	EID4039 In an in vitro study, a H3122 cell line expressing L1196M mutation in the ALK portion of the EML4-ALK fusion protein was associated with resistance to crizotinib treatment, as compared to H3122 cells … (full text at CIViC) PMID 27565908 · Lucena-Araujo et al., 2016 · Open in CIViC	civic

Lung Adenocarcinoma9

EML4::ALK Fusion

Crizotinib

Predictive

Supports Sensitivity Response

accepted

EID262

A 28 year-old patient with non-small cell lung cancer that failed conventional therapy was found to harbor the EML4-ALK (E13;A20) fusion using reverse transcription PCR. Treatment with 250mg crizotini… (full text at CIViC)

PMID 20979473 · Choi et al., 2010 · Open in CIViC

civic

EML4::ALK Fusion AND ABCB1 Overexpression

Alectinib + LorlatinibSubstitutes

Predictive

Does Not Support Resistance

accepted

EID10016

EML4-ALK fusion positive lung adenocarcinoma cell lines with high expression of P-gp (ABCB1 gene) (H3122 and the newly established JFCR013-2) were found to be resistant to crizotinib and ceritinib. P-… (full text at CIViC)

PMID 26870817 · Katayama et al., 2016 · Open in CIViC

civic

EML4::ALK Fusion AND ABCB1 Overexpression

Ceritinib + CrizotinibSubstitutes

Predictive

Supports Resistance

accepted

EID7869

EML4-ALK fusion positive lung adenocarcinoma cell lines (H3122 and the newly established JFCR013-2) with high expression of P-gp (ABCB1 gene) were found to be resistant to crizotinib and ceritinib. P… (full text at CIViC)

PMID 26870817 · Katayama et al., 2016 · Open in CIViC

civic

EML4::ALK Fusion AND ALK C1156Y

Crizotinib

Predictive

Supports Resistance

accepted

EID236

A 28 year-old patient with T4N3M1 stage lung adenocarcinoma harboring an EML4-ALK variant 1 fusion was treated with crizotinib after failing conventional therapy. The patient achieved a partial respon… (full text at CIViC)

PMID 20979473 · Choi et al., 2010 · Open in CIViC

civic

EML4::ALK Fusion AND ALK C1156Y

Crizotinib

Predictive

Supports Resistance

accepted

EID4046

In a lung adenocarcinoma cancer patient with an EML4-ALK gene rearrangement (a known sensitizing alteration to crizotinib) and an ALK C1156Y co-mutation, ALK C1156Y was reported to be refractory to cr… (full text at CIViC)

PMID 27045755 · Saber et al., 2016 · Open in CIViC

civic

EML4::ALK Fusion AND ALK G1269A

Crizotinib

Predictive

Supports Resistance

accepted

EID4620

In a lung adenocarcinoma cancer patient with an EML4-ALK gene rearrangement (a known sensitizing alteration to crizotinib) and an ALK G1269A co-mutation, ALK G1269A was reported to be refractory to cr… (full text at CIViC)

PMID 27045755 · Saber et al., 2016 · Open in CIViC

civic

EML4::ALK Fusion AND ALK L1196M

Crizotinib

Predictive

Supports Resistance

accepted

EID237

A 28 year-old patient with non-small cell lung cancer was found to harbor the EML4-ALK (E13;A20) fusion using reverse transcription PCR. Treatment with 250mg crizotinib twice daily resulted in rapid i… (full text at CIViC)

PMID 20979473 · Choi et al., 2010 · Open in CIViC

civic

EML4::ALK Fusion AND ALK L1196M

Crizotinib

Predictive

Supports Resistance

submitted

EID4040

In a stage IV Hodgkin's lymphoma patient with metastatic lung adenocarcinoma harboring an EML4-ALK gene rearrangement (a known sensitizing alteration to crizotinib) and an ALK L1196M�co-mutation, ALK … (full text at CIViC)

PMID 27507192 · Zhang et al., 2017 · Open in CIViC

civic

EML4::ALK Fusion AND ALK L1196M

Crizotinib

Predictive

Supports Resistance

submitted

EID4039

In an in vitro study, a H3122 cell line expressing L1196M mutation in the ALK portion of the EML4-ALK fusion protein was associated with resistance to crizotinib treatment, as compared to H3122 cells … (full text at CIViC)

PMID 27565908 · Lucena-Araujo et al., 2016 · Open in CIViC

civic

Lung Large Cell Carcinoma1
EML4::ALK Fusion AND ALK I1171S	Crizotinib	Predictive	D	Supports Resistance	2	submitted	EID4794 In an in vitro study, a FL5.12 cell line expressing NPM1-ALK or EML4-ALK (known sensitizing alterations to crizotinib) and an ALK I1171S co-mutation, demonstrated resistance to crizotinib treatment (I… (full text at CIViC) PMID 27009859 · Amin et al., 2016 · Open in CIViC	civic

Lung Large Cell Carcinoma1

EML4::ALK Fusion AND ALK I1171S

Crizotinib

Predictive

Supports Resistance

submitted

EID4794

In an in vitro study, a FL5.12 cell line expressing NPM1-ALK or EML4-ALK (known sensitizing alterations to crizotinib) and an ALK I1171S co-mutation, demonstrated resistance to crizotinib treatment (I… (full text at CIViC)

PMID 27009859 · Amin et al., 2016 · Open in CIViC

civic

Lung Non-Small Cell Carcinoma38
EML4::ALK Fusion	Crizotinib	Predictive	C	Supports Sensitivity Response	4	accepted	EID1207 In the PROFILE 1001 study of crizotinib in 82 patients with ALK-rearranged NSCLC, 31 patients with sufficient tumor material were tested using RT-PCR for the presence of certain EML4-ALK variants. 13… (full text at CIViC) PMID 20979469 · Kwak et al., 2010 · Open in CIViC	civic
EML4::ALK Fusion	Alvespimycin + CrizotinibCombination	Predictive	D	Supports Sensitivity Response	2	accepted	EID1206 Transduction of Ba/F3 cells with EML4-ALK variant 1 causes IL3 independent growth. Incubation of EML4-ALK variant 1 transduced Ba/F3 cells with Hsp90 inhibitor 17-DMAG caused cell death that was rever… (full text at CIViC) PMID 22912387 · Heuckmann et al., 2012 · Open in CIViC	civic
EML4::ALK Fusion	Crizotinib + Retaspimycin HydrochlorideCombination	Predictive	D	Supports Sensitivity Response	4	accepted	EID1203 In preclinical work using H3122 NSCLC cells which contain the EML4-ALK variant 1, administration of the Hsp90 inhibitor IPI-504 caused marked decrease of EML4-ALK protein levels at concentrations lowe… (full text at CIViC) PMID 21258415 · Normant et al., 2011 · Open in CIViC	civic
EML4::ALK Fusion	Lorlatinib	Predictive	D	Supports Sensitivity Response	2	accepted	EID1332 EML4-ALK variant 1 containing H-3122 NSCLC cells were treated with second generation ALK inhibitor PF-06463922. PF-06463922 was 125x more potent at reducing cell viability than crizotinib. Control neu… (full text at CIViC) PMID 26554404 · Infarinato et al., 2016 · Open in CIViC	civic
EML4::ALK Fusion	WHI-P154	Predictive	D	Supports Sensitivity Response	5	accepted	EID1188 A retroviral cDNA expression library was constructed using a lung adenocarcinoma specimen from a 67 year old NSCLC patient, and transfected into mouse 3T3 fibroblasts which were assessed for transform… (full text at CIViC) PMID 17625570 · Soda et al., 2007 · Open in CIViC	civic
EML4::ALK Fusion AND ALK Amplification	Crizotinib	Predictive	C	Supports Resistance	3	accepted	EID766 This study analyzed patients with non small cell lung cancer (NSCLC) who were positive for EML4-ALK fusions (ALK+) and progressed on crizotinib monotherapy. One out of 11 patients with acquired crizot… (full text at CIViC) PMID 22235099 · Doebele et al., 2012 · Open in CIViC	civic
EML4::ALK Fusion AND ALK Amplification	Crizotinib	Predictive	C	Supports Resistance	2	accepted	EID767 One patient with ALK-rearranged non-small cell lung cancer and an acquired resistance to crizotinib showed new ALK amplification (4.1 fold increase compared to pre-crizotinib specimen as measured by F… (full text at CIViC) PMID 23344087 · Kim et al., 2013 · Open in CIViC	civic
EML4::ALK Fusion AND ALK Amplification	Crizotinib	Predictive	D	Supports Resistance	3	accepted	EID440 Amplification of wild-type EML4-ALK in the non-small cell lung carcinoma cell line, H3122, caused resistance to crizotinib. PMID 22277784 · Katayama et al., 2012 · Open in CIViC	civic
EML4::ALK Fusion AND ALK C1156Y	Crizotinib	Predictive	C	Supports Resistance	2	submitted	EID4042 In a non-small cell lung cancer patient with a liver metastatic tumor harboring an ALK gene rearrangement and an ALK C1156Y co-mutation, ALK C1156Y was reported to be refractory to 7-month crizotinib … (full text at CIViC) PMID 23434628 · Huang et al., 2013 · Open in CIViC	civic
EML4::ALK Fusion AND ALK C1156Y	Crizotinib	Predictive	D	Supports Resistance	4	accepted	EID1346 EML4-ALK variant 3 containing NSCLC cell line H2228 xenografts in SCID beige mice were treated with increasing doses of crizotinib up to 100 mg/kg per day by oral gavage. At approximately 40 days tumo… (full text at CIViC) PMID 24675041 · Friboulet et al., 2014 · Open in CIViC	civic
EML4::ALK Fusion AND ALK C1156Y	Crizotinib	Predictive	D	Supports Resistance	2	submitted	EID4043 In an in vitro study, H3122 cells expressing EML4-ALK fusion (a known sensitizing alteration to crizotinib) and an ALK C1156Y co-mutation demonstrated resistance to crizotinib treatment (240 nmol/L vs… (full text at CIViC) PMID 21791641 · Sasaki et al., 2011 · Open in CIViC	civic
EML4::ALK Fusion AND ALK C1156Y	Crizotinib	Predictive	D	Supports Resistance	2	submitted	EID4044 In an in vitro study, a Ba/F3 cell line expressing EML4-ALK fusion (a known sensitizing alteration to crizotinib) and an ALK C1156Y co-mutation demonstrated resistance to crizotinib treatment (180 nm… (full text at CIViC) PMID 22235099 · Doebele et al., 2012 · Open in CIViC	civic
EML4::ALK Fusion AND ALK C1156Y	Ceritinib + Crizotinib + LuminespibSequential	Predictive	C	Supports Resistance	3	accepted	EID841 In this case report, a patient with metastatic, ALK-rearranged NSCLC with C1156Y mutation had tumor progression under sequential treatment with first crizotinib, then ceritinib and finally AUY922. Sub… (full text at CIViC) PMID 26698910 · Shaw et al., 2016 · Open in CIViC	civic
EML4::ALK Fusion AND ALK C1156Y	Ensartinib	Predictive	B	Supports Sensitivity Response	3	submitted	EID8860 In this multicentre phase II study of ALK-positive NSCLC patients that progressed on crizotinib, the safety and efficacy of 225mg daily ensartinib was assessed. Objective responses were seen in 76 (52… (full text at CIViC) PMID 31628085 · Yang et al., 2020 · Open in CIViC	civic
EML4::ALK Fusion AND ALK C1156Y	Lorlatinib	Predictive	C	Supports Sensitivity Response	3	accepted	EID842 Case report of a patient with metastatic ALK-rearranged NSCLC after progression under sequential crizotinib, ceritinib, HSP90 inhibitor AUY922 and chemotherapy followed by crizotinib again. Third gene… (full text at CIViC) PMID 26698910 · Shaw et al., 2016 · Open in CIViC	civic
EML4::ALK Fusion AND ALK F1174L	Crizotinib	Predictive	D	Supports Resistance	3	accepted	EID33 Ba/F3 cells expressing the EML4-ALK fusion containing an F1174L mutation were more resistant to crizotinib treatment than Ba/F3 cells expressing EML4-ALK without this mutation. PMID 21030459 · Sasaki et al., 2010 · Open in CIViC	civic
EML4::ALK Fusion AND ALK F1245C	Ceritinib	Predictive	C	Supports Sensitivity Response	3	accepted	EID1338 A 52 year old male never smoker was diagnosed with stage IV NSCLC adenocarcinoma and was treated with chemotherapy with eventual disease progression. He tested positive for ALK rearrangement via break… (full text at CIViC) PMID 26775591 · Kodityal et al., 2016 · Open in CIViC	civic
EML4::ALK Fusion AND ALK F1245C	Crizotinib	Predictive	C	Supports Resistance	2	accepted	EID1339 A 52 year old with a non-smoking history was diagnosed with stage IV NSCLC-adenocarcinoma and treated with chemotherapy. Upon disease progression, the initial diagnostic biopsy tested positive for AL… (full text at CIViC) PMID 26775591 · Kodityal et al., 2016 · Open in CIViC	civic
EML4::ALK Fusion AND ALK G1202del	Ceritinib	Predictive	C	Supports Resistance	4	submitted	EID7599 In an analysis of 83 ALK positive NSCLC patients treated with multiple ALK inhibitors, one patient biopsy showed G1202del mutation after progressing on ceritinib. In addition, Ba/F3 cell lines express… (full text at CIViC) PMID 27432227 · Gainor et al., 2016 · Open in CIViC	civic
EML4::ALK Fusion AND ALK G1202R	Ceritinib	Predictive	D	Supports Resistance	4	accepted	EID1345 Ba/F3 cells expressing EML4-ALK variant 1 with ALK G1202R mutation were assessed for ceritinib sensitivity. Crizotinib was shown to confer significantly more potency than ceritinib (43-fold decrease i… (full text at CIViC) PMID 24675041 · Friboulet et al., 2014 · Open in CIViC	civic
EML4::ALK Fusion AND ALK G1202R	Crizotinib	Predictive	D	Supports Resistance	4	accepted	EID441 The G1202R mutation in the EML4-ALK fusion was found to confer resistance to crizotinib in Ba/F3 cells. PMID 22277784 · Katayama et al., 2012 · Open in CIViC	civic
EML4::ALK Fusion AND ALK G1202R	Crizotinib	Predictive	D	Supports Resistance	1	submitted	EID4625 In an in vitro study, a Ba/F3 cell line expressing EML4-ALK fusion (a known sensitizing alteration to crizotinib) and an ALK G1202R co-mutation, demonstrated resistance to crizotinib treatment compare… (full text at CIViC) PMID 24675041 · Friboulet et al., 2014 · Open in CIViC	civic
EML4::ALK Fusion AND ALK G1202R	Tanespimycin	Predictive	D	Supports Sensitivity Response	2	accepted	EID1352 The G1202R ALK mutation was found in a crizotinib-resistant ALK-rearranged NSCLC, and the mutant ALK fusion was further characterized in Ba/F3 cells. EML4-ALK variant 1 with G1202R mutation was expres… (full text at CIViC) PMID 22277784 · Katayama et al., 2012 · Open in CIViC	civic
EML4::ALK Fusion AND ALK G1202R AND ALK L1196M	Lorlatinib	Predictive	C	Supports Resistance	3	submitted	EID7591 Repeat biopsies were taken for 20 ALK-positive NSCLC patients, including 11 with pre- and post-lorlatinib biopsies. 19 of 20 patients received crizotinib and at least one second line ALK inhibitor. On… (full text at CIViC) PMID 29650534 · Yoda et al., 2018 · Open in CIViC	civic
EML4::ALK Fusion AND ALK G1269A	Crizotinib	Predictive	C	Supports Resistance	4	accepted	EID764 This study analyzed patients with non small cell lung cancer (NSCLC) who were positive for EML4-ALK fusions (ALK+) and progressed on crizotinib monotherapy. One ALK+ patient harbored the common E6;A20… (full text at CIViC) PMID 22235099 · Doebele et al., 2012 · Open in CIViC	civic
EML4::ALK Fusion AND ALK G1269A	Crizotinib	Predictive	C	Supports Resistance	3	accepted	EID765 2 out of 7 patients with an acquired resistance to crizotinib had a G1269A mutation. One of these patients also harbored a L1196M mutation. In vitro follow-up showed reduced crizotinib-induced ALK dep… (full text at CIViC) PMID 23344087 · Kim et al., 2013 · Open in CIViC	civic
EML4::ALK Fusion AND ALK G1269A	Crizotinib	Predictive	C	Supports Resistance	2	submitted	EID4619 In a non-small cell lung cancer patient with acquired crizotinib resistance, the tumor had an EML4-ALK gene rearrangement (a known sensitizing alteration to crizotinib) and an ALK G1269A co-mutation. … (full text at CIViC) PMID 24675041 · Friboulet et al., 2014 · Open in CIViC	civic
EML4::ALK Fusion AND ALK I1171S	Alectinib + CrizotinibSequential	Predictive	C	Supports Resistance	2	accepted	EID1484 Case study describes a caucasian male (age 38) never smoker presenting with stage IV non-small cell lung cancer with an ALK rearrangement. Patient was given crizotinib and exhibited a partial response… (full text at CIViC) PMID 25393796 · Ou et al., 2014 · Open in CIViC	civic
EML4::ALK Fusion AND ALK L1152R	Crizotinib	Predictive	C	Supports Resistance	4	accepted	EID763 Case-report of a patient with an acquired EML4::ALK L1152R mutation and resistance to crizotinib treatment. The L1152R variant was not present in the pre-crizotinib sample. A cell line model also show… (full text at CIViC) PMID 21791641 · Sasaki et al., 2011 · Open in CIViC	civic
EML4::ALK Fusion AND ALK L1196M	Alectinib	Predictive	D	Supports Sensitivity Response	3	accepted	EID141 CH5424802 treatment resulted in significant tumor regression in xenograft models produced from Ba/F3 cells expressing EML4-ALK or EML4-ALK with the L1196M mutation. PMID 21575866 · Sakamoto et al., 2011 · Open in CIViC	civic
EML4::ALK Fusion AND ALK L1196M	Ceritinib	Predictive	D	Supports Sensitivity Response	4	accepted	EID1341 The crizotinib-resistant MGH045 cell line with EML4-ALK L1196M was treated with crizotinib or ceritinib. In nude mice with MGH045 xenografts, tumor response to crizotinib did not differ appreciably fr… (full text at CIViC) PMID 24675041 · Friboulet et al., 2014 · Open in CIViC	civic
EML4::ALK Fusion AND ALK L1196M	Crizotinib	Predictive	C	Supports Resistance	3	submitted	EID4034 This study analyzed patients with non small cell lung cancer (NSCLC) who were positive for EML4-ALK fusions (ALK+) and progressed on crizotinib monotherapy. Two ALK+ patients had ALK L1196M co-mutatio… (full text at CIViC) PMID 22235099 · Doebele et al., 2012 · Open in CIViC	civic
EML4::ALK Fusion AND ALK L1196M	Crizotinib	Predictive	C	Supports Resistance	2	submitted	EID4036 In a stage IV non-small cell lung cancer patient with an EML4-ALK gene rearrangement (a known sensitizing alteration to crizotinib) and an ALK L1196M co-mutation, ALK L1196M was reported to be refract… (full text at CIViC) PMID 23344087 · Kim et al., 2013 · Open in CIViC	civic
EML4::ALK Fusion AND ALK L1196M	Crizotinib	Predictive	D	Supports Resistance	4	accepted	EID442 The L1196M mutation in the EML4-ALK fusion was found to confer resistance to crizotinib in Ba/F3 cells. PMID 22277784 · Katayama et al., 2012 · Open in CIViC	civic
EML4::ALK Fusion AND ALK L1196M	Crizotinib	Predictive	D	Supports Resistance	2	submitted	EID4037 In an in vitro study, a Ba/F3 cell line expressing EML4-ALK fusion (a known sensitizing alteration to crizotinib) and an ALK L1196M co-mutation, demonstrated resistance to crizotinib treatment compare… (full text at CIViC) PMID 21502504 · Katayama et al., 2011 · Open in CIViC	civic
EML4::ALK Fusion AND ALK L1196M	Crizotinib	Predictive	D	Supports Resistance	2	submitted	EID4038 In an in vitro study, a Ba/F3 cell line expressing EML4-ALK fusion (a known sensitizing alteration to crizotinib) and an ALK L1196M co-mutation, demonstrated resistance to crizotinib treatment compare… (full text at CIViC) PMID 21948233 · Heuckmann et al., 2011 · Open in CIViC	civic
EML4::ALK Fusion AND ALK L1196M	Ensartinib	Predictive	B	Supports Sensitivity Response	4	submitted	EID7865 Treatment of crizotinib resistant patients harboring ALK L1196M by ensartinib resulted in an objective response rate of 25% and disease control rate of 91% in a multicentre phase II clinical trial. PMID 31628085 · Yang et al., 2020 · Open in CIViC	civic
EML4::ALK Fusion AND ALK L1198F AND ALK C1156Y	Crizotinib	Predictive	C	Supports Sensitivity Response	4	accepted	EID844 Case report of a patient with metastatic ALK-rearranged NSCLC. After developing resistance to first and second line ALK inhibitors mediated by a C1156Y mutation, the patient had a partial response wit… (full text at CIViC) PMID 26698910 · Shaw et al., 2016 · Open in CIViC	civic

Lung Non-Small Cell Carcinoma38

EML4::ALK Fusion

Crizotinib

Predictive

Supports Sensitivity Response

accepted

EID1207

In the PROFILE 1001 study of crizotinib in 82 patients with ALK-rearranged NSCLC, 31 patients with sufficient tumor material were tested using RT-PCR for the presence of certain EML4-ALK variants. 13… (full text at CIViC)

PMID 20979469 · Kwak et al., 2010 · Open in CIViC

civic

EML4::ALK Fusion

Alvespimycin + CrizotinibCombination

Predictive

Supports Sensitivity Response

accepted

EID1206

Transduction of Ba/F3 cells with EML4-ALK variant 1 causes IL3 independent growth. Incubation of EML4-ALK variant 1 transduced Ba/F3 cells with Hsp90 inhibitor 17-DMAG caused cell death that was rever… (full text at CIViC)

PMID 22912387 · Heuckmann et al., 2012 · Open in CIViC

civic

EML4::ALK Fusion

Crizotinib + Retaspimycin HydrochlorideCombination

Predictive

Supports Sensitivity Response

accepted

EID1203

In preclinical work using H3122 NSCLC cells which contain the EML4-ALK variant 1, administration of the Hsp90 inhibitor IPI-504 caused marked decrease of EML4-ALK protein levels at concentrations lowe… (full text at CIViC)

PMID 21258415 · Normant et al., 2011 · Open in CIViC

civic

EML4::ALK Fusion

Lorlatinib

Predictive

Supports Sensitivity Response

accepted

EID1332

EML4-ALK variant 1 containing H-3122 NSCLC cells were treated with second generation ALK inhibitor PF-06463922. PF-06463922 was 125x more potent at reducing cell viability than crizotinib. Control neu… (full text at CIViC)

PMID 26554404 · Infarinato et al., 2016 · Open in CIViC

civic

EML4::ALK Fusion

WHI-P154

Predictive

Supports Sensitivity Response

accepted

EID1188

A retroviral cDNA expression library was constructed using a lung adenocarcinoma specimen from a 67 year old NSCLC patient, and transfected into mouse 3T3 fibroblasts which were assessed for transform… (full text at CIViC)

PMID 17625570 · Soda et al., 2007 · Open in CIViC

civic

EML4::ALK Fusion AND ALK Amplification

Crizotinib

Predictive

Supports Resistance

accepted

EID766

This study analyzed patients with non small cell lung cancer (NSCLC) who were positive for EML4-ALK fusions (ALK+) and progressed on crizotinib monotherapy. One out of 11 patients with acquired crizot… (full text at CIViC)

PMID 22235099 · Doebele et al., 2012 · Open in CIViC

civic

EML4::ALK Fusion AND ALK Amplification

Crizotinib

Predictive

Supports Resistance

accepted

EID767

One patient with ALK-rearranged non-small cell lung cancer and an acquired resistance to crizotinib showed new ALK amplification (4.1 fold increase compared to pre-crizotinib specimen as measured by F… (full text at CIViC)

PMID 23344087 · Kim et al., 2013 · Open in CIViC

civic

EML4::ALK Fusion AND ALK Amplification

Crizotinib

Predictive

Supports Resistance

accepted

EID440

Amplification of wild-type EML4-ALK in the non-small cell lung carcinoma cell line, H3122, caused resistance to crizotinib.

PMID 22277784 · Katayama et al., 2012 · Open in CIViC

civic

EML4::ALK Fusion AND ALK C1156Y

Crizotinib

Predictive

Supports Resistance

submitted

EID4042

In a non-small cell lung cancer patient with a liver metastatic tumor harboring an ALK gene rearrangement and an ALK C1156Y co-mutation, ALK C1156Y was reported to be refractory to 7-month crizotinib … (full text at CIViC)

PMID 23434628 · Huang et al., 2013 · Open in CIViC

civic

EML4::ALK Fusion AND ALK C1156Y

Crizotinib

Predictive

Supports Resistance

accepted

EID1346

EML4-ALK variant 3 containing NSCLC cell line H2228 xenografts in SCID beige mice were treated with increasing doses of crizotinib up to 100 mg/kg per day by oral gavage. At approximately 40 days tumo… (full text at CIViC)

PMID 24675041 · Friboulet et al., 2014 · Open in CIViC

civic

EML4::ALK Fusion AND ALK C1156Y

Crizotinib

Predictive

Supports Resistance

submitted

EID4043

In an in vitro study, H3122 cells expressing EML4-ALK fusion (a known sensitizing alteration to crizotinib) and an ALK C1156Y co-mutation demonstrated resistance to crizotinib treatment (240 nmol/L vs… (full text at CIViC)

PMID 21791641 · Sasaki et al., 2011 · Open in CIViC

civic

EML4::ALK Fusion AND ALK C1156Y

Crizotinib

Predictive

Supports Resistance

submitted

EID4044

In an in vitro study, a Ba/F3 cell line expressing EML4-ALK fusion (a known sensitizing alteration to crizotinib) and an ALK C1156Y co-mutation demonstrated resistance to crizotinib treatment (180 nm… (full text at CIViC)

PMID 22235099 · Doebele et al., 2012 · Open in CIViC

civic

EML4::ALK Fusion AND ALK C1156Y

Ceritinib + Crizotinib + LuminespibSequential

Predictive

Supports Resistance

accepted

EID841

In this case report, a patient with metastatic, ALK-rearranged NSCLC with C1156Y mutation had tumor progression under sequential treatment with first crizotinib, then ceritinib and finally AUY922. Sub… (full text at CIViC)

PMID 26698910 · Shaw et al., 2016 · Open in CIViC

civic

EML4::ALK Fusion AND ALK C1156Y

Ensartinib

Predictive

Supports Sensitivity Response

submitted

EID8860

In this multicentre phase II study of ALK-positive NSCLC patients that progressed on crizotinib, the safety and efficacy of 225mg daily ensartinib was assessed. Objective responses were seen in 76 (52… (full text at CIViC)

PMID 31628085 · Yang et al., 2020 · Open in CIViC

civic

EML4::ALK Fusion AND ALK C1156Y

Lorlatinib

Predictive

Supports Sensitivity Response

accepted

EID842

Case report of a patient with metastatic ALK-rearranged NSCLC after progression under sequential crizotinib, ceritinib, HSP90 inhibitor AUY922 and chemotherapy followed by crizotinib again. Third gene… (full text at CIViC)

PMID 26698910 · Shaw et al., 2016 · Open in CIViC

civic

EML4::ALK Fusion AND ALK F1174L

Crizotinib

Predictive

Supports Resistance

accepted

EID33

Ba/F3 cells expressing the EML4-ALK fusion containing an F1174L mutation were more resistant to crizotinib treatment than Ba/F3 cells expressing EML4-ALK without this mutation.

PMID 21030459 · Sasaki et al., 2010 · Open in CIViC

civic

EML4::ALK Fusion AND ALK F1245C

Ceritinib

Predictive

Supports Sensitivity Response

accepted

EID1338

A 52 year old male never smoker was diagnosed with stage IV NSCLC adenocarcinoma and was treated with chemotherapy with eventual disease progression. He tested positive for ALK rearrangement via break… (full text at CIViC)

PMID 26775591 · Kodityal et al., 2016 · Open in CIViC

civic

EML4::ALK Fusion AND ALK F1245C

Crizotinib

Predictive

Supports Resistance

accepted

EID1339

A 52 year old with a non-smoking history was diagnosed with stage IV NSCLC-adenocarcinoma and treated with chemotherapy. Upon disease progression, the initial diagnostic biopsy tested positive for AL… (full text at CIViC)

PMID 26775591 · Kodityal et al., 2016 · Open in CIViC

civic

EML4::ALK Fusion AND ALK G1202del

Ceritinib

Predictive

Supports Resistance

submitted

EID7599

In an analysis of 83 ALK positive NSCLC patients treated with multiple ALK inhibitors, one patient biopsy showed G1202del mutation after progressing on ceritinib. In addition, Ba/F3 cell lines express… (full text at CIViC)

PMID 27432227 · Gainor et al., 2016 · Open in CIViC

civic

EML4::ALK Fusion AND ALK G1202R

Ceritinib

Predictive

Supports Resistance

accepted

EID1345

Ba/F3 cells expressing EML4-ALK variant 1 with ALK G1202R mutation were assessed for ceritinib sensitivity. Crizotinib was shown to confer significantly more potency than ceritinib (43-fold decrease i… (full text at CIViC)

PMID 24675041 · Friboulet et al., 2014 · Open in CIViC

civic

EML4::ALK Fusion AND ALK G1202R

Crizotinib

Predictive

Supports Resistance

accepted

EID441

The G1202R mutation in the EML4-ALK fusion was found to confer resistance to crizotinib in Ba/F3 cells.

PMID 22277784 · Katayama et al., 2012 · Open in CIViC

civic

EML4::ALK Fusion AND ALK G1202R

Crizotinib

Predictive

Supports Resistance

submitted

EID4625

In an in vitro study, a Ba/F3 cell line expressing EML4-ALK fusion (a known sensitizing alteration to crizotinib) and an ALK G1202R co-mutation, demonstrated resistance to crizotinib treatment compare… (full text at CIViC)

PMID 24675041 · Friboulet et al., 2014 · Open in CIViC

civic

EML4::ALK Fusion AND ALK G1202R

Tanespimycin

Predictive

Supports Sensitivity Response

accepted

EID1352

The G1202R ALK mutation was found in a crizotinib-resistant ALK-rearranged NSCLC, and the mutant ALK fusion was further characterized in Ba/F3 cells. EML4-ALK variant 1 with G1202R mutation was expres… (full text at CIViC)

PMID 22277784 · Katayama et al., 2012 · Open in CIViC

civic

EML4::ALK Fusion AND ALK G1202R AND ALK L1196M

Lorlatinib

Predictive

Supports Resistance

submitted

EID7591

Repeat biopsies were taken for 20 ALK-positive NSCLC patients, including 11 with pre- and post-lorlatinib biopsies. 19 of 20 patients received crizotinib and at least one second line ALK inhibitor. On… (full text at CIViC)

PMID 29650534 · Yoda et al., 2018 · Open in CIViC

civic

EML4::ALK Fusion AND ALK G1269A

Crizotinib

Predictive

Supports Resistance

accepted

EID764

This study analyzed patients with non small cell lung cancer (NSCLC) who were positive for EML4-ALK fusions (ALK+) and progressed on crizotinib monotherapy. One ALK+ patient harbored the common E6;A20… (full text at CIViC)

PMID 22235099 · Doebele et al., 2012 · Open in CIViC

civic

EML4::ALK Fusion AND ALK G1269A

Crizotinib

Predictive

Supports Resistance

accepted

EID765

2 out of 7 patients with an acquired resistance to crizotinib had a G1269A mutation. One of these patients also harbored a L1196M mutation. In vitro follow-up showed reduced crizotinib-induced ALK dep… (full text at CIViC)

PMID 23344087 · Kim et al., 2013 · Open in CIViC

civic

EML4::ALK Fusion AND ALK G1269A

Crizotinib

Predictive

Supports Resistance

submitted

EID4619

In a non-small cell lung cancer patient with acquired crizotinib resistance, the tumor had an EML4-ALK gene rearrangement (a known sensitizing alteration to crizotinib) and an ALK G1269A co-mutation. … (full text at CIViC)

PMID 24675041 · Friboulet et al., 2014 · Open in CIViC

civic

EML4::ALK Fusion AND ALK I1171S

Alectinib + CrizotinibSequential

Predictive

Supports Resistance

accepted

EID1484

Case study describes a caucasian male (age 38) never smoker presenting with stage IV non-small cell lung cancer with an ALK rearrangement. Patient was given crizotinib and exhibited a partial response… (full text at CIViC)

PMID 25393796 · Ou et al., 2014 · Open in CIViC

civic

EML4::ALK Fusion AND ALK L1152R

Crizotinib

Predictive

Supports Resistance

accepted

EID763

Case-report of a patient with an acquired EML4::ALK L1152R mutation and resistance to crizotinib treatment. The L1152R variant was not present in the pre-crizotinib sample. A cell line model also show… (full text at CIViC)

PMID 21791641 · Sasaki et al., 2011 · Open in CIViC

civic

EML4::ALK Fusion AND ALK L1196M

Alectinib

Predictive

Supports Sensitivity Response

accepted

EID141

CH5424802 treatment resulted in significant tumor regression in xenograft models produced from Ba/F3 cells expressing EML4-ALK or EML4-ALK with the L1196M mutation.

PMID 21575866 · Sakamoto et al., 2011 · Open in CIViC

civic

EML4::ALK Fusion AND ALK L1196M

Ceritinib

Predictive

Supports Sensitivity Response

accepted

EID1341

The crizotinib-resistant MGH045 cell line with EML4-ALK L1196M was treated with crizotinib or ceritinib. In nude mice with MGH045 xenografts, tumor response to crizotinib did not differ appreciably fr… (full text at CIViC)

PMID 24675041 · Friboulet et al., 2014 · Open in CIViC

civic

EML4::ALK Fusion AND ALK L1196M

Crizotinib

Predictive

Supports Resistance

submitted

EID4034

This study analyzed patients with non small cell lung cancer (NSCLC) who were positive for EML4-ALK fusions (ALK+) and progressed on crizotinib monotherapy. Two ALK+ patients had ALK L1196M co-mutatio… (full text at CIViC)

PMID 22235099 · Doebele et al., 2012 · Open in CIViC

civic

EML4::ALK Fusion AND ALK L1196M

Crizotinib

Predictive

Supports Resistance

submitted

EID4036

In a stage IV non-small cell lung cancer patient with an EML4-ALK gene rearrangement (a known sensitizing alteration to crizotinib) and an ALK L1196M co-mutation, ALK L1196M was reported to be refract… (full text at CIViC)

PMID 23344087 · Kim et al., 2013 · Open in CIViC

civic

EML4::ALK Fusion AND ALK L1196M

Crizotinib

Predictive

Supports Resistance

accepted

EID442

The L1196M mutation in the EML4-ALK fusion was found to confer resistance to crizotinib in Ba/F3 cells.

PMID 22277784 · Katayama et al., 2012 · Open in CIViC

civic

EML4::ALK Fusion AND ALK L1196M

Crizotinib

Predictive

Supports Resistance

submitted

EID4037

In an in vitro study, a Ba/F3 cell line expressing EML4-ALK fusion (a known sensitizing alteration to crizotinib) and an ALK L1196M co-mutation, demonstrated resistance to crizotinib treatment compare… (full text at CIViC)

PMID 21502504 · Katayama et al., 2011 · Open in CIViC

civic

EML4::ALK Fusion AND ALK L1196M

Crizotinib

Predictive

Supports Resistance

submitted

EID4038

PMID 21948233 · Heuckmann et al., 2011 · Open in CIViC

civic

EML4::ALK Fusion AND ALK L1196M

Ensartinib

Predictive

Supports Sensitivity Response

submitted

EID7865

Treatment of crizotinib resistant patients harboring ALK L1196M by ensartinib resulted in an objective response rate of 25% and disease control rate of 91% in a multicentre phase II clinical trial.

PMID 31628085 · Yang et al., 2020 · Open in CIViC

civic

EML4::ALK Fusion AND ALK L1198F AND ALK C1156Y

Crizotinib

Predictive

Supports Sensitivity Response

accepted

EID844

Case report of a patient with metastatic ALK-rearranged NSCLC. After developing resistance to first and second line ALK inhibitors mediated by a C1156Y mutation, the patient had a partial response wit… (full text at CIViC)

PMID 26698910 · Shaw et al., 2016 · Open in CIViC

civic

Evidence by cancer (118 items)

Clinical significance (0)