ALK rearrangement / fusion — biomarker · CancerIndex

Biomarker · Gene alteration

ALK rearrangement / fusion

ALK gene rearrangements (most often EML4-ALK) detected by FISH, immunohistochemistry or sequencing; used as a predictive marker for ALK inhibitors in non-small cell lung cancer and some lymphomas.

CI-BIO-00000013ALK graph →NCIt C142135 Tumor-agnostic · 3 approval rows

Also calledALK-positive · ALK rearrangement · EML4-ALK · ALK fusion

Tissue-agnostic indications

Approval rows flagged tumor-agnostic (3)

Entrectinib EU EMA · Jul 31, 2020 · drug in derived setRegulatory approved
Entrectinib US FDA · Oct 20, 2023 · drug in derived setRegulatory approved
Entrectinib US FDA · Aug 15, 2019 · drug in derived setRegulatory approved

The flag is the source's (openFDA label text), never inferred; the full indication text of each row is in the Approvals section below.

Derived

Associated cancers (20)

Cancers mapped in ACCEPTED CIViC predictive, prognostic or diagnostic items whose variant (molecular markers) or gene (gene-level markers) is in this biomarker's scope. Counts by type and native level; each row links to the cancer's evidence tab.

Computedrule biomarker-links-v1

Cancer	Items	Predictive	Prognostic	Diagnostic	Levels A / B / C / D / E
Lung Non-Small Cell Carcinoma	80	80	—	—	9 / 12 / 23 / 35 / 1
Neuroblastoma	18	18	—	—	0 / 0 / 6 / 12 / 0
Malignant Neoplasm	10	10	—

Derived

Drugs with predictive evidence (16)

Therapies named in in-scope PREDICTIVE CIViC items, plus targets of PREDICTS_RESPONSE_TO knowledge edges from in-scope variants. Sensitivity and resistance are counted separately and never merged into a verdict.

Computedrule biomarker-links-v1

Drug	CIViC items	Sensitivity	Resistance	Best level	Edges (S / R)	Cancer context
CrizotinibSmall Molecule	73	45	28	A	45 / 52	Anaplastic Large Cell Lymphoma, Colorectal Adenocarcinoma, Cutaneous Melanoma, Diffuse Large B-Cell Lymphoma +8
AlectinibSmall Molecule	23	13	10	A	14 / 17	Lung Adenocarcinoma, Lung Non-Small Cell Carcinoma, Malignant Neoplasm, Neuroblastoma +3
CeritinibSmall Molecule	18	15	3	A	21 / 5	Colon Adenocarcinoma, Lung Adenocarcinoma, Lung Non-Small Cell Carcinoma, Malignant Neoplasm +1
LorlatinibSmall Molecule	10	7	3	B	10 / 7	Lung Adenocarcinoma, Lung Non-Small Cell Carcinoma, Neuroblastoma, Pleural Malignant Mesothelioma
ALK Inhibitor TAE684	9	7	2	D	7 / 3	Diffuse Large B-Cell Lymphoma, Lung Non-Small Cell Carcinoma, Neuroblastoma
BrigatinibSmall Molecule	6	5	1	A	7 / 2	Lung Non-Small Cell Carcinoma, Malignant Neoplasm, Neuroblastoma
EntrectinibSmall Molecule	5	5	—	B	4 / 0	Inflammatory Myofibroblastic Tumor, Malignant Colorectal Neoplasm, Malignant Neoplasm, Mucosal Melanoma +1
AlvespimycinSmall Molecule	3	3	—	D	2 / 0	Lung Non-Small Cell Carcinoma
TanespimycinSmall Molecule	2	2	—	D	4 / 0	Lung Non-Small Cell Carcinoma
Retaspimycin HydrochlorideSmall Molecule	2	2	—	C	2 / 0	Lung Non-Small Cell Carcinoma
LuminespibSmall Molecule	1	—	1	C	0 / 2	Lung Non-Small Cell Carcinoma
2,4-pyrimidinediamine	1	1	—	D	1 / 0	Lung Non-Small Cell Carcinoma
AZD3463	1	1	—	D	1 / 0	Neuroblastoma
ErlotinibSmall Molecule	1	—	1	C	0 / 1	Lung Acinar Adenocarcinoma
PemetrexedSmall Molecule	1	1	—	B	1 / 0	Lung Non-Small Cell Carcinoma
WHI-P154	1	1	—	D	1 / 0	Lung Non-Small Cell Carcinoma

Curatedcivic items and knowledge edges as curated at the source.

Curated evidence

Predictive evidence items (148)

ACCEPTED CIViC predictive items in scope, grouped by molecular profile and therapy with native level, direction and cancer context. 50 per page.

civicCuratedShowing 1–50 of 148 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
ALK Fusion19
Crizotinib	Anaplastic Large Cell Lymphoma	Predictive	A	Supports Sensitivity Response	4	accepted	EID11218 This trial enrolled 26 patients with anaplastic large cell lymphoma (ALCL). The groups received twice daily crizotinib at doses of either 165 or 280 mg/m2. 83% of the 165 mg/m2 ALCL patients had a com… (full text at CIViC) PMID 28787259 · Mossé et al., 2017 · Open in CIViC	civic
〃	Anaplastic Large Cell Lymphoma	Predictive	B	Supports Sensitivity Response	3	accepted	EID7361 In this phase I/II study, 26 patients with relapsed/refractory ALK-positive ALCL were administered crizotinib orally twice daily in 28-day cycles as a single agent for an indefinite duration. Patients… (full text at CIViC) PMID 28787259 · Mossé et al., 2017 · Open in CIViC	civic
〃	Anaplastic Large Cell Lymphoma	Predictive	C	Supports Sensitivity Response	4	accepted	EID1240 Crizotinib at 250mg daily was given to two patients with relapsed ALK-rearranged anaplastic large cell lymphoma (ALCL). Patient one, 26 yrs old, had been treated with the CHOP-15 chemotherapy regimen,… (full text at CIViC) PMID 21345110 · Gambacorti-Passerini et al., 2011 · Open in CIViC	civic
〃	Colorectal Adenocarcinoma	Predictive	E	Supports Sensitivity Response	1	accepted	EID1334 26 colorectal adenocarcinoma samples were run on Affymetrix human Exon 1.0 arrays and a computational method that assessed differential 5' and 3' gene expression for each gene was used to find potenti… (full text at CIViC) PMID 19737969 · Lin et al., 2009 · Open in CIViC	civic
〃	Diffuse Large B-Cell LymphomaCURATED_BROADER	Predictive	C	Supports Sensitivity Response	2	accepted	EID1264 A 27 year old female patient with advanced-stage IV, CD20 negative diffuse large B cell lymphoma (DLBCL). ALK rearrangement was determined by FISH, but the ALK fusion partner was not determined due to… (full text at CIViC) PMID 24330038 · Wass et al., 2014 · Open in CIViC	civic
〃	Inflammatory Myofibroblastic Tumor	Predictive	A	Supports Sensitivity Response	3	accepted	EID11122 9 patients with ALK-positive inflammatory myofibroblastic tumour (IMT) enrolled in the PROFILE 1013 (NCT01121588) phase 1b single-arm, open-label, multi-centre study received crizotinib. ORR was 67% f… (full text at CIViC) PMID 29352732 · Gambacorti-Passerini et al., 2018 · Open in CIViC	civic
〃	Inflammatory Myofibroblastic Tumor	Predictive	B	Supports Sensitivity Response	3	accepted	EID1243 As part of a phase 1 dose-escalation trial (NCT00939770), seven patients between ages 12 months and 22 years with relapsed or refractory inflammatory myofibroblastic tumors with ALK-rearrangement were… (full text at CIViC) PMID 23598171 · Mossé et al., 2013 · Open in CIViC	civic
〃	Inflammatory Myofibroblastic Tumor	Predictive	B	Supports Sensitivity Response	3	accepted	EID7362 In this phase I/II study, 14 patients with metastatic or inoperable ALK-positive IMT were administered crizotinib orally twice daily in 28-day cycles as a single agent for an indefinite duration. The … (full text at CIViC) PMID 28787259 · Mossé et al., 2017 · Open in CIViC	civic
〃	Lung Adenocarcinoma	Predictive	C	Supports Sensitivity Response	3	accepted	EID1691 In an evaluation of a patient with crizotinib-sensitive lung adenocarcinoma, an EML4-ALK-E13;A20 rearrangement was identified using CGP. The patient attained a reduction in the target lesions by 14.2… (full text at CIViC) PMID 25922291 · Le et al., 2015 · Open in CIViC	civic
Alectinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	5	accepted	EID1282 In this Phase II trial of 87 patients (NCT01871805), alectinib was assayed for safety and efficacy in ALK positive NSCLC that had progressed on crizotinib. Of 69 patients with measurable disease, 35 a… (full text at CIViC) PMID 26708155 · Shaw et al., 2016 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	5	accepted	EID7284 In a phase 3 trial, 303 patients with NSCLC with ALK fusion were randomly assigned to alectinib arm (N=152) or crizotinib arm (N=151). PFS was significantly longer with alectinib than with crizotinib … (full text at CIViC) PMID 28586279 · Peters et al., 2017 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	5	accepted	EID8657 A randomized phase 3 trial (J-ALEX) of 207 Japanese ALK-positive NSCLC patients compared the efficacy and safety of alectinib (300mg twice daily) and crizotinib (250mg twice daily) in the first-line s… (full text at CIViC) PMID 28501140 · Hida et al., 2017 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	5	accepted	EID12012 In this global phase 3 trial, 257 patients with ALK-positive Non-Small-Cell Lung Cancer were treated with either alectinib (n = 130) or chemotherapy (n = 127). 93.8 % of the patients who had received … (full text at CIViC) PMID 38598794 · Wu et al., 2024 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	3	accepted	EID1272 In this initial report of a single-arm Phase I and II study (JapicCTI-101264) of alectinib (CH5424802), 46 patients with advanced or metastatic ALK-rearranged non small cell lung cancer (NSCLC) were a… (full text at CIViC) PMID 23639470 · Seto et al., 2013 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	4	accepted	EID1279 In this Phase I trial (NCT01588028) in 47 patients, alectinib was assessed for its effectiveness in treating locally advanced or metastatic ALK-positive NSCLC that had progressed or been resistant to … (full text at CIViC) PMID 25153538 · Gadgeel et al., 2014 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	C	Supports Sensitivity Response	3	accepted	EID1273 In this case study of a critically ill 29 year old male nonsmoker with advanced metastatic ALK-positive NSCLC, alectinib (CH5424802), was administered as first line treatment. Where most clinical tria… (full text at CIViC) PMID 26938871 · Yoshida et al., 2016 · Open in CIViC	civic
Brigatinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	5	accepted	EID11121 The phase III ALTA-1L open-label randomized trial examined 275 NSCLC patients given brigatinib (137 patients) vs crizotinib (138 patients). Patients were ALK fusion positive by an FDA-approved diagno… (full text at CIViC) PMID 32780660 · Camidge et al., 2020 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	4	accepted	EID4835 In a phase II randomized trial we evaluated two regimens of Brigatinib in Crizotinib-refractory ALK-pos. NSCLC. They were randomly assigned (1:1) to oral Brigatinib 90 mg once daily (arm A) or 180 mg … (full text at CIViC) PMID 28475456 · Kim et al., 2017 · Open in CIViC	civic
Ceritinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	5	accepted	EID7285 In a phase 3 trial, patients with previously treatmented NSCLC with ALK fusion were randomly assigned to ceritinib or chemotherapy. Ceritinib showed a significant improvement in median PFS compared w… (full text at CIViC) PMID 28602779 · Shaw et al., 2017 · Open in CIViC	civic
ALK Fusion2
Crizotinib	Anaplastic Large Cell Lymphoma	Predictive	B	Supports Sensitivity Response	4	accepted	EID1241 In the second part of this Phase I study NCT00939770, nine patients between the ages of 12 months and 22 years with anaplastic large cell lymphoma (ALCL), who were refractory to treatment and for whom… (full text at CIViC) PMID 23598171 · Mossé et al., 2013 · Open in CIViC	civic
〃	Anaplastic Large Cell Lymphoma	Predictive	D	Supports Sensitivity Response	5	accepted	EID1239 NPM-ALK in anaplastic large cell lymphoma (ALCL) was the first ALK-fusion to be discovered and characterized. In this study, targeted activity against NPM-ALK by the ALK and MET inhibitor crizotinib … (full text at CIViC) PMID 18089725 · Christensen et al., 2007 · Open in CIViC	civic
ALK Fusion1
Ceritinib	Colon Adenocarcinoma	Predictive	C	Supports Sensitivity Response	3	accepted	EID5952 Patients with metastatic colorectal cancer with STRN-ALK fusion, sporadic microsatellite instability high (MSI-H) and KRAS R164Q received ALK inhibitor ceritinib. After pts received ceritinib perinumb… (full text at CIViC) PMID 26933125 · Yakirevich et al., 2016 · Open in CIViC	civic
ALK Alternative Transcript (ATI)1
Crizotinib	Cutaneous MelanomaALIAS	Predictive	C	Supports Sensitivity Response	4	accepted	EID1936 Expression of an alternative ALK transcript (ATI), encompassing exons 20–29 preceded by ~400 base pairs (bp) of intron 19, but not exons 1–19 was identified in three samples of thyroid cancer and mela… (full text at CIViC) PMID 26444240 · Wiesner et al., 2015 · Open in CIViC	civic
ALK Fusion2
ALK Inhibitor TAE684	Diffuse Large B-Cell LymphomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	4	accepted	EID1261 A cell line called LM1 was established from the bone marrow of a 13 year old female patient with relapsed CLTC-ALK positive diffuse large B-cell lymphoma (DLBCL). The patient had been heavily treated … (full text at CIViC) PMID 21494621 · Cerchietti et al., 2011 · Open in CIViC	civic
Crizotinib	Diffuse Large B-Cell LymphomaCURATED_BROADER	Predictive	C	Supports Sensitivity Response	3	accepted	EID1265 A 21 year old male presented with lymphadenopathy and a low density mass in pancreas. Histopathological analysis showed diffuse tumor cell infiltrate (CD20/EMA negative) with cytoplasmic ALK. RT-PCR i… (full text at CIViC) PMID 26221234 · Li et al., 2015 · Open in CIViC	civic
ALK F1174L + ALK Fusion1
Crizotinib	Inflammatory Myofibroblastic Tumor	Predictive	C	Supports Resistance	3	accepted	EID32 In a patient with RANBP2::ALK-positive inflammatory myofibroblastic tumor, acquisition of the ALK F1174L mutation following crizotinib treatment was associated with acquired resistance. Ba/F3 studies … (full text at CIViC) PMID 21030459 · Sasaki et al., 2010 · Open in CIViC	civic
ALK Fusion1
Crizotinib	Inflammatory Myofibroblastic Tumor	Predictive	C	Supports Sensitivity Response	4	accepted	EID1244 ALK-rearrangements are seen in 50% of inflammatory myofibroblastic tumor (IMT) cases. A 44 year old man was diagnosed with IMT. He was treated with surgery and catheter placement for administration o… (full text at CIViC) PMID 20979472 · Butrynski et al., 2010 · Open in CIViC	civic
ALK Fusion1
Entrectinib	Inflammatory Myofibroblastic Tumor	Predictive	C	Supports Sensitivity Response	3	accepted	EID11856 In a phase 1/2 trial of entrectinib in pediatric patients, tumors with fusions in NTRK, ROS1, or ALK had an overall response (ORR) of 57.7% (95% CI; 36.9-76.7). This included a patient with inflammat… (full text at CIViC) PMID 35395680 · Desai et al., 2022 · Open in CIViC	civic
ALK Fusion2
Erlotinib	Lung Acinar Adenocarcinoma	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 · Tanaka et al., 2012 · Open in CIViC	civic
Crizotinib	Lung Adenocarcinoma	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
ABCB1 Overexpression + ALK FusionALK ABCB12
Alectinib + LorlatinibSubstitutes	Lung Adenocarcinoma	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
Ceritinib + CrizotinibSubstitutes	Lung Adenocarcinoma	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
ALK C1156Y + ALK Fusion2
Crizotinib	Lung Adenocarcinoma	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
〃	Lung Adenocarcinoma	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
ALK L1196M + ALK Fusion2
Crizotinib	Lung Adenocarcinoma	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
Alectinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	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
ALK G1202R + ALK Fusion1
Crizotinib	Lung Adenocarcinoma	Predictive	C	Supports Resistance	3	accepted	EID1357 A patient with ALK-rearranged lung adenocarcinoma responded to crizotinib treatment and then had relapse. Biopsy was taken within half a month and total DNA was extracted from the sample. Exons 20-28,… (full text at CIViC) PMID 22277784 · Katayama et al., 2012 · Open in CIViC	civic
ALK G1269A + ALK Fusion1
Crizotinib	Lung Adenocarcinoma	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
ALK e6::e204
2,4-pyrimidinediamine	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	4	accepted	EID1192 In a cohort of 75 NSCLC patients that had tested positive for 3 EML4-ALK rearrangements, two individuals were identified via RT-PCR with a novel EML4-ALK translocation involving the first 6 exons of E… (full text at CIViC) PMID 18593892 · Choi et al., 2008 · Open in CIViC	civic
ALK Inhibitor TAE684	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	2	accepted	EID1194 In a panel of 602 cancer cell lines, 3/134 NSCLC cell lines showed <0.5% cell viability following treatment with the ALK inhibitor TAE684. Of these, NCI-H2228 harbored EML4-ALK variant 3a/b (EML4 exon… (full text at CIViC) PMID 18451166 · McDermott et al., 2008 · Open in CIViC	civic
〃
ALK I11713
Alectinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	C	Supports Resistance	4	accepted	EID1283 The I1171T mutation in ALK fusions was found in a NSCLC patient shown positive for ALK rearrangement via break apart FISH assay, who progressed after 8 months of crizotinib, and then progressed again … (full text at CIViC) PMID 25228534 · Katayama et al., 2014 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	C	Supports Resistance	2	accepted	EID1367 A 51 year old female never-smoker was diagnosed with stage IV NSCLC with liver metastases. ALK rearrangement was verified via FISH. She was treated with crizotinib at 250 mg twice daily but discontinu… (full text at CIViC) PMID 25736571 · Ou et al., 2015 · Open in CIViC	civic
ALK Inhibitor TAE684	Lung Non-Small Cell Carcinoma
ALK V1180L + ALK Fusion3
Alectinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	3	accepted	EID1286 The EML4 ALK variant 1 containing NSCLC cell line H3122 is highly sensitive to alectinib, and an alectinib resistant derivative cell line H3122 CHR-A1 was generated by incubation of H3122 in increasin… (full text at CIViC) PMID 25228534 · Katayama et al., 2014 · Open in CIViC	civic
ALK Inhibitor TAE684	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	accepted	EID1290 The V1180L mutation in the kinase domain of rearranged ALK was found in an alectinib resistant cell line named H3122 CHR-A1, which was derived from the alectinib sensitive EML4-ALK variant 1 containin… (full text at CIViC) PMID 25228534 · Katayama et al., 2014 · Open in CIViC	civic
Brigatinib	Lung Non-Small Cell Carcinoma
ALK T1151dup + ALK Fusion2
Alectinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	3	accepted	EID1347 Ba/F3 cells expressing EML4-ALK with 1151 Tins treated with alectinib had an IC50 of 165.7 nM, 16x higher than those expressing EML4-ALK wildtype variant 1. EML4-ALK variant 1 expressing H3122 NSCLC c… (full text at CIViC) PMID 22277784 · Katayama et al., 2012 · Open in CIViC	civic
ALK Inhibitor TAE684	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	3	accepted	EID1348 Treatment of Ba/F3 cells expressing EML4-ALK 1151 insT with TAE684 produced an IC50 value (28.3 nM) 20x higher cells expressing EML4-ALK wildtype variant 1. The crizotinib resistant clones were produc… (full text at CIViC) PMID 22277784 · Katayama et al., 2012 · Open in CIViC	civic

Regulatory

Approvals mentioning the linked drugs (178)

Approval records of the derived drug set, plus records whose indication text names this biomarker. Each record names its authority, jurisdiction, indication text and status — a drug approved in one jurisdiction for one indication is not 'approved' in general, and an approval listed here is not necessarily restricted to this biomarker.

Computedrule biomarker-links-v1

emaRegulatory50 approval records from 3 sources (hover a row badge for its dataset) · authority, jurisdiction and indication text as published.

Drug	Jurisdiction · authority	Cancer	Indication	Status	Approval date	Source
Entrectinib	EU EMA	Tumor-agnosticLung Non-Small Cell Carcinoma	Rozlytrek as monotherapy is indicated for the treatment of adult and paediatric patients 12 years of age and older with solid tumours expressing a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, who have a disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity, and who have not received a prior NTRK inhibitor who have no satisfactory treatment options. Rozlytrek as monotherapy is indicated for the treatment of adult patients with ROS1 positive, advanced non small cell lung cancer (NSCLC) not previously treated with ROS1 inhibitors.conditional	approved	Jul 31, 2020	ema
Entrectinib	US FDA	Tumor-agnostic	Adult and pediatric patients older than 1 month of age with solid tumors that: have a neurotrophic tyrosine receptor kinase ( NTRK) gene fusion, as detected by an FDA-approved test without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.accelerated	approved	Oct 20, 2023	openfda

4 records matched on indication text only (drug not in the derived set). Health Canada DIN rows carry no indication text and only match by drug.

Clinical trials

Active trials (226)

Trials with an active ClinicalTrials.gov status, an intervention mapped to a derived drug and a condition mapped to an associated cancer. 105 recruiting · 85 active phase 3 · 867 in any status. Most recently updated first, 50 per page.

Computedrule biomarker-links-v1

clinicaltrialsPublishedShowing 201–226 of 226 active studies · status and phase as posted by the registrant; each row links to the study record.

NCT	Title	Status	Phase	Enrollment (n)	Sponsor	Countries	Last update	Source
NCT06690541	Real-world Study of Local Therapy Changes During 1L Lorlatinib in Unresectable ALK+ NSCLC(COMLORLA)	not yet recruiting	—	100	Peking University Cancer Hospital & InstituteOTHER	0	Nov 15, 2024	clinicaltrials
NCT04127110	Activity of Lorlatinib Based on ALK Resistance Mutations Detected on Blood in ALK Positive NSCLC Patients(ALKALINE)	active not recruiting	Phase 2	68	European Organisation for Research and Treatment of Cancer - EORTCNETWORK	7	Nov 5, 2024	clinicaltrials
NCT04322890	Treatment Strategies and Survival Outcome for Non-small Cell Lung Cancer With Oncogenic Mutation(PIKACHU)	recruiting	Phase 2	6,000	Hunan Province Tumor HospitalOTHER	1	Oct 22, 2024	clinicaltrials
NCT05501665	Split Course Adaptive Radiation Therapy With Pembrolizumab With/Without Chemotherapy for Treating Stage IV Lung Cancer	recruiting	Phase 1 / Phase 2	25	Vanderbilt-Ingram Cancer CenterOTHER	1	Oct 17, 2024	clinicaltrials
NCT05487391	A Study of QL1706 Combined With Platinum-containing Chemotherapy in Adjuvant Treatment of Stage II-IIIB Non-small Cell Lung Cancer After Complete Surgical Resection.	recruiting	Phase 3	632	Qilu Pharmaceutical Co., Ltd.INDUSTRY	1	Oct 15, 2024	clinicaltrials
NCT05014464	ALK Tyrosine Kinase Inhibitors in ALK-rearranged Advanced Squamous Cell Carcinoma(ATPase)	recruiting	Phase 2	90	Hunan Province Tumor HospitalOTHER	1	Sep 20, 2024	clinicaltrials
NCT05766800	Induction Therapy With PD-1 Antibody Combined With Platinum-based Doublet Chemotherapy for Locally-advanced Non-small Cell Lung Cancer	recruiting	Phase 2	100	Shanghai Pulmonary Hospital, Shanghai, ChinaOTHER	1	Sep 19, 2024	clinicaltrials
NCT06594874	A Phase Ib Study of HS-10370 in Addition to Other Anti-cancer Therapies in Participants with KRAS G12C Mutation Advanced Solid Tumors	not yet recruiting	Phase 1	350	Jiangsu Hansoh Pharmaceutical Co., Ltd.INDUSTRY	1	Sep 19, 2024	clinicaltrials
NCT05015010	Alectinib in Neo-adjuvant Treatment of Stage III NSCLC(ALNEO)	active not recruiting	Phase 2	33	Gruppo Oncologico Italiano di Ricerca ClinicaOTHER	1	Aug 9, 2024	clinicaltrials
NCT06532149	ERectile Dysfunctions, gOnadotoxicity and Sexual Health Assessment in Men With Lung Cancer(EROS)	recruiting	—	80	Fondazione Policlinico Universitario Agostino Gemelli IRCCSOTHER	1	Aug 9, 2024	clinicaltrials
NCT05159245	The Finnish National Study to Facilitate Patient Access to Targeted Anti-cancer Drugs(FINPROVE)	recruiting	Phase 2	250	Helsinki University Central HospitalOTHER	1	Jul 15, 2024	clinicaltrials
NCT05525338	Comparison of Standard Dose Alectinib to Alectinib in Adjusted Dose Based on Alectinib Bloodlevels(ADAPT ALEC)	recruiting	Phase 4	196	University Medical Center GroningenOTHER	2	May 13, 2024	clinicaltrials
NCT06380348	JMT101 in Combination With Osimertinib, Versus Cisplatin-pemetrexed in Participants With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) Characterized by Epithermal Growth Factor Receptor (EGFR) Exon 20ins Mutations	not yet recruiting	Phase 3	398	Shanghai JMT-Bio Inc.INDUSTRY	0	Apr 23, 2024	clinicaltrials
NCT06254599	A Study Of SY-3505 Versus Crizotinib In First Line Treatment Of Patients With ALK-Positive NSCLC	not yet recruiting	Phase 3	255	Shouyao Holdings (Beijing) Co. LTDOTHER	1	Feb 12, 2024	clinicaltrials
NCT02925234	The Drug Rediscovery Protocol (DRUP Trial)(DRUP)	recruiting	Phase 2	1,550	The Netherlands Cancer InstituteOTHER	1	Jan 24, 2024	clinicaltrials
NCT05011487	Neoadjuvant Osimertinib + Chemotherapy for EGFR-mutant Stage III NSCLC(NOCE01)	recruiting	Phase 2	30	Sun Yat-sen UniversityOTHER	1	Jan 16, 2024	clinicaltrials
NCT06109402	Perioperative Immunotherpay Versus Adjuvant Immunotherapy for Resectable Non-small Cell Lung Cancer	not yet recruiting	Phase 2	160	Shanghai Pulmonary Hospital, Shanghai, ChinaOTHER	1	Dec 19, 2023	clinicaltrials
NCT06001151	Cadonilimab (AK104) Plus Chemotherapy as First-line Treatment in Non-squamous Non-Small Cell Lung Cancer (NSCLC) Patients With Programmed Cell Death Ligand 1 (PD-L1) Negative(ACHELOUS)	recruiting	Phase 2	49	Qian ChuOTHER	1	Aug 21, 2023	clinicaltrials
NCT05990127	A Study of AK104/Tislelizumab With Chemotherapy as First-line Treatment in PD-L1 TPS < 1% Non-small Cell Lung Cancer	not yet recruiting	Phase 3	642	AkesoINDUSTRY	1	Aug 14, 2023	clinicaltrials
NCT05891080	Neoadjuvant Therapy With Toripalimab and JS004 Combined With Platinum-based Doublet Chemotherapy for Resectable or Potentially Resectable Stage III Non-small Cell Lung Cancer: A Randomised Controlled, Open-label, Phase 2 Trial	not yet recruiting	Phase 2	124	Shanghai Pulmonary Hospital, Shanghai, ChinaOTHER	0	Jun 6, 2023	clinicaltrials
NCT05800340	Neoadjuvant Immunotherapy in Rare Mutations Localized NSCLC	recruiting	Phase 2	30	Guangdong Provincial People's HospitalOTHER	1	Apr 5, 2023	clinicaltrials
NCT05725200	Study to Investigate Outcome of Individualized Treatment in Patients With Metastatic Colorectal Cancer(EVIDENT)	recruiting	Phase 2	40	Oslo University HospitalOTHER	1	Feb 21, 2023	clinicaltrials
NCT04762459	Efficacy and Safety of Almonertinib Combined With or Without Chemotherapy as an Adjuvant Treatment for Stage II-IIIA Non-small Cell Lung Carcinoma Following Complete Tumour Resection(APEX)	enrolling by invitation	Phase 3	606	Chinese Academy of Medical SciencesOTHER	1	Feb 24, 2022	clinicaltrials
NCT05132985	Neoadjuvant Icotinib With Chemotherapy for Epidermal Growth Factor Receptor(EGFR)-Mutated Resectable Lung Adenocarcinoma	not yet recruiting	Phase 2	45	Liaoning Cancer Hospital & InstituteOTHER	1	Dec 10, 2021	clinicaltrials
NCT05104788	A Study of Icotinib With Chemotherapy as Neoadjuvant Therapy for Patients With EGFRm Positive Resectable Non-Small Cell Lung Cancer(NeoIpower)	recruiting	Phase 2	27	Peking University Cancer Hospital & InstituteOTHER	1	Nov 3, 2021	clinicaltrials
NCT04153734	Pembrolizumab + Platinum Doublets Without Radiation for Programmed Death-ligand 1 (PD-L1) ≥50% Locally Advanced NSCLC(Evolution)	not yet recruiting	Phase 2	21	Kobe Minimally Invasive Cancer CenterOTHER	0	Nov 6, 2019	clinicaltrials

A study listed here tests a linked drug in a linked cancer; it does not necessarily select participants on this biomarker.

Atezolizumab

EU EMA

—

Urothelial carcinoma Tecentriq as monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC): after prior platinum containing chemotherapy, or who are considered cisplatin ineligible, and whose tumours have a PD-L1 expression ≥ 5% (see section 5.1). Early-stage non-small cell lung cancer (NSCLC) Tecentriq as monotherapy is indicated as adjuvant treatment following complete resection and platinum-based chemotherapy for adult patients with NSCLC with a high risk of recurrence whose tumours have PD-L1 expression on ≥ 50% of tumour cells (TC) and who do not have EGFR mutant or ALK positive NSCLC (see section 5.1 for selection criteria). Advanced NSCLC  Tecentriq, in combination with bevacizumab, paclitaxel and carboplatin, is indicated for the first-line treatment of adult patients with metastatic non-squamous non small cell lung cancer (NSCLC). In patients with EGFR mutant or ALK-positive NSCLC, Tecentriq, in combination with bevacizumab, paclitaxel and carboplatin, is indicated only after failure of appropriate targeted therapies (see section 5.1).Tecentriq, in combination with nab paclitaxel and carboplatin, is indicated for the first line treatment of adult patients with metastatic non-squamous NSCLC who do not have EGFR mutant or ALK positive NSCLC (see section 5.1).Tecentriq as monotherapy is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumours have a PD-L1 expression ≥ 50% tumour cells (TC) or ≥ 10% tumour-infiltrating immune cells (IC) and who do not have EGFR mutant or ALK-positive NSCLC (see section 5.1).Tecentriq as monotherapy is indicated for the first-line treatment of adult patients with advanced NSCLC who are ineligible for platinum-based therapy (see section 5.1 for selection criteria).Tecentriq as monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic NSCLC after prior chemotherapy. Patients with EGFR mutant or ALK positive NSCLC should also have received targeted therapies before receiving Tecentriq (see section 5.1).Small cell lung cancer (SCLC)Tecentriq, in combination with carboplatin and etoposide, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) (see section 5.1). Triple-negative breast cancer (TNBC)Tecentriq in combination with nab-paclitaxel is indicated for the treatment of adult patients with unresectable locally advanced or metastatic TNBC whose tumours have PD-L1 expression ≥ 1% and who have not received prior chemotherapy for metastatic disease.Hepatocellular carcinomaTecentriq, in combination with bevacizumab, is indicated for the treatment of adult patients with advanced or unresectable hepatocellular carcinoma (HCC) who have not received prior systemic therapy (see section 5.1). Urothelial carcinoma (UC) Tecentriq as monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic UC: after prior platinum containing chemotherapy, or who are considered cisplatin ineligible, and whose tumours have a PD-L1 expression ≥ 5% (see section 5.1). Early-stage non-small cell lung cancer (NSCLC) Tecentriq as monotherapy is indicated as adjuvant treatment following complete resection and platinum-based chemotherapy for adult patients with NSCLC with a high risk of recurrence whose tumours have PD-L1 expression on ≥ 50% of tumour cells (TC) and who do not have EGFR mutant or ALK positive NSCLC (see section 5.1 for selection criteria). Advanced NSCLC  Tecentriq, in combination with bevacizumab, paclitaxel and carboplatin, is indicated for the first-line treatment of adult patients with metastatic non-squamous NSCLC. In patients with EGFR mutant or ALK-positive NSCLC, Tecentriq, in combination with bevacizumab, paclitaxel and carboplatin, is indicated only after failure of appropriate target…

approved

Sep 20, 2017

ema

Durvalumab

EU EMA

—

Non-Small Cell Lung Cancer (NSCLC)Imfinzi in combination with platinum-based chemotherapy as neoadjuvant treatment, followed by Imfinzi as monotherapy as adjuvant treatment, is indicated for the treatment of adults with resectable NSCLC at high risk of recurrence and no EGFR mutations or ALK rearrangements (for selection criteria, see section 5.1). Imfinzi as monotherapy is indicated for the treatment of locally advanced, unresectable non small cell lung cancer (NSCLC) in adults whose tumours express PD-L1 on ≥ 1% of tumour cells and whose disease has not progressed following platinum based chemoradiation therapy (see section 5.1).Imfinzi in combination with tremelimumab and platinum-based chemotherapy is indicated for the first-line treatment of adults with metastatic NSCLC with no sensitising EGFR mutations or ALK positive mutations. Small Cell Lung Cancer (SCLC)Imfinzi in combination with etoposide and either carboplatin or cisplatin is indicated for the first-line treatment of adults with extensive-stage small cell lung cancer (ES-SCLC). Biliary Tract Cancer (BTC)Imfinzi in combination with gemcitabine and cisplatin is indicated for the first line treatment of adults with unresectable or metastatic biliary tract cancer (BTC). Hepatocellular Carcinoma (HCC)Imfinzi as monotherapy is indicated for the first line treatment of adults with advanced or unresectable hepatocellular carcinoma (HCC).  Imfinzi in combination with tremelimumab is indicated for the first line treatment of adults with advanced or unresectable hepatocellular carcinoma (HCC). Endometrial Cancer Imfinzi in combination with carboplatin and paclitaxel is indicated for the first-line treatment of adults with primary advanced or recurrent endometrial cancer who are candidates for systemic therapy, followed by maintenance treatment with: - Imfinzi as monotherapy in endometrial cancer that is mismatch repair deficient (dMMR) - Imfinzi in combination with olaparib in endometrial cancer that is mismatch repair proficient (pMMR). Muscle Invasive Bladder Cancer (MIBC) Imfinzi in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by Imfinzi as monotherapy adjuvant treatment after radical cystectomy, is indicated for the treatment of adults with resectable muscle invasive bladder cancer (MIBC). Gastric or Gastro-oesophageal Junction Adenocarcinoma (GC/GEJC) Imfinzi in combination with FLOT chemotherapy as neoadjuvant and adjuvant treatment, followed by adjuvant Imfinzi monotherapy, is indicated for the treatment of adults with resectable gastric or gastro‑oesophageal junction adenocarcinoma.

approved

Sep 21, 2018

ema

Approval rows flagged tumor-agnostic (3)

Associated cancers (20)

Drugs with predictive evidence (16)

Predictive evidence items (148)

Approvals mentioning the linked drugs (178)

Active trials (226)

Linked publications (82)