ROS1 rearrangement / fusion

ROS1 gene rearrangements detected by FISH, immunohistochemistry or sequencing; used as a predictive marker for ROS1-directed tyrosine kinase inhibitors in non-small cell lung cancer.

CI-BIO-00000014ROS1 graph →NCIt C131071 Tumor-agnostic · 4 approval rows

Also calledROS1-positive · ROS1 rearrangement · CD74-ROS1

Tissue-agnostic indications

Approval rows flagged tumor-agnostic (4)

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
Repotrectinib EU EMA · Jan 13, 2025 · matched on indication textRegulatory 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 (11)

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	19	19	—	—	6 / 0 / 1 / 12 / 0
Lung Adenocarcinoma	5	5	—	—	0 / 0 / 4 / 1 / 0
Inflammatory Myofibroblastic Tumor	3

Derived

Drugs with predictive evidence (10)

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	17	9	8	A	9 / 15	Colorectal Adenocarcinoma, Inflammatory Myofibroblastic Tumor, Lung Adenocarcinoma, Lung Non-Small Cell Carcinoma +2
EntrectinibSmall Molecule	8	8	—	A	8 / 0	Desmoplastic Infantile Astrocytoma, Diffuse Midline Glioma, H3 K27-Altered, Inflammatory Myofibroblastic Tumor, Low Grade Glioma +2
ForetinibSmall Molecule	5	4	1	D	8 / 2	Lung Non-Small Cell Carcinoma
LorlatinibSmall Molecule	3	3	—	D	5 / 0	Glioblastoma, Lung Non-Small Cell Carcinoma
CabozantinibSmall Molecule	2	2	—	D	4 / 0	Lung Non-Small Cell Carcinoma
CeritinibSmall Molecule	2	1	1	C	1 / 2	Lung Adenocarcinoma, Lung Non-Small Cell Carcinoma
ALK Inhibitor TAE684	1	—	1	D	0 / 2	Lung Non-Small Cell Carcinoma
AZD3463	1	—	1	D	0 / 2	Lung Non-Small Cell Carcinoma
BrigatinibSmall Molecule	1	—	1	D	0 / 2	Lung Non-Small Cell Carcinoma
DS-6501b	1	1	—	D	2 / 0	Lung Adenocarcinoma

Curatedcivic items and knowledge edges as curated at the source.

Curated evidence

Predictive evidence items (35)

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

civicCuratedShowing 1–35 of 35 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
ROS1 Fusion8
Crizotinib	Colorectal Adenocarcinoma	Predictive	E	Supports Sensitivity Response	2	accepted	EID1301 A tissue microarray of 268 patients with histologically confirmed colorectal adenocarcinoma was performed to search for ROS1 gene fusion events to guide potential targeted therapy in future cases. Bre… (full text at CIViC) PMID 24296758 · Aisner et al., 2014 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	4	accepted	EID688 An expansion cohort of a phase-1 Crizotinib study found a 72% objective response rate among 50 patients with ROS1 rearrangement. The study did not compare to patients without rearrangement that were t… (full text at CIViC) PMID 25264305 · Shaw et al., 2014 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	3	accepted	EID1030 In a retrospective study, 30 patients were evaluated after crizotinib treatment for stage IV NSCLC confirmed for ROS1 rearrangement. On crizotinib, 24 of the patients achieved objective responses incl… (full text at CIViC) PMID 25667280 · Mazières et al., 2015 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	5	accepted	EID7282 In the ongoing phase 1 study PROFILE 1001, NSCLC patients with ROS1 rearrangement confirmed by FISH or RT-PCR received crizotinib 250mg twice daily. Among 53 patients, the ORR was 72% (95% CI, 58% to … (full text at CIViC) PMID 30980071 · Shaw et al., 2019 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	4	accepted	EID7933 A phase 2 clinical trial studied the efficacy of Crizotinib in East Asian NSCLC patients positive for ROS1 rearrangements (detected by RT-PCR AmoyDx assay) and negative for ALK1 rearrangements. Of the… (full text at CIViC) PMID 29596029 · Wu et al., 2018 · Open in CIViC	civic
Entrectinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	3	accepted	EID2951 Two phase I studies included 119 patients with advanced or metastatic solid tumors, which included 28 patients with ROS1 rearrangements (n=28) where the overall safety and antitumor activity of entrec… (full text at CIViC) PMID 28183697 · Drilon et al., 2017 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	5	accepted	EID11123 Describes a meta-analysis of three separate phase I or II trials: ALKA-372-001, STARTRK-1, and STARTRK-2. All of these evaluate entrectinib in ROS-1 fusion-positive NSCLC (locally advanced or metastat… (full text at CIViC) PMID 31838015 · Drilon et al., 2020 · Open in CIViC	civic
Crizotinib	Minimally Invasive Lung AdenocarcinomaALIAS	Predictive	C	Supports Sensitivity Response	3	accepted	EID1443 Study describes a 31-year old male, never-smoker patient with advanced NSCLC. Testing did not indicate tumor had EGFR mutation or ALK rearrangement. First line erlotininb did not yield a response. Aft… (full text at CIViC) PMID 22215748 · Bergethon et al., 2012 · Open in CIViC	civic
ROS1 Fusion1
Entrectinib	Desmoplastic Infantile AstrocytomaALIAS	Predictive	C	Supports Sensitivity Response	3	accepted	EID11850 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 one patient (3 yo) with … (full text at CIViC) PMID 35395680 · Desai et al., 2022 · Open in CIViC	civic
ROS1 Fusion3
Entrectinib	Diffuse Midline Glioma, H3 K27-Altered	Predictive	C	Supports Sensitivity Response	3	accepted	EID11849 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 one patient (4 yo) with … (full text at CIViC) PMID 35395680 · Desai et al., 2022 · Open in CIViC	civic
〃	Low Grade Glioma	Predictive	C	Supports Sensitivity Response	1	accepted	EID11855 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 one patient (8 yo) with … (full text at CIViC) PMID 35395680 · Desai et al., 2022 · Open in CIViC	civic
〃	Melanoma	Predictive	C	Supports Sensitivity Response	4
ROS1 e7::e351
Lorlatinib	GlioblastomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	accepted	EID7483 Ectopic expression of GOPC–ROS1 in Ba/F3 cells induced cytokine-independent growth whereas overexpression of ROS1 alone did not. Using a series of tyrosine kinase inhibitors, lorlatinib was the most e… (full text at CIViC) PMID 30171048 · Davare et al., 2018 · Open in CIViC	civic
ROS1 Fusion3
Crizotinib	Inflammatory Myofibroblastic Tumor	Predictive	C	Supports Sensitivity Response	3	accepted	EID1444 Case report of a pediatric patient with treatment-refactory inflammatory myofibroblastic tumor negative for ALK expression and rearrangement. Next generation sequencing of the patient revealed a TFG-R… (full text at CIViC) PMID 24875859 · Lovly et al., 2014 · Open in CIViC	civic
Entrectinib	Inflammatory Myofibroblastic Tumor	Predictive	C	Supports Sensitivity Response	2	accepted	EID11860 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
〃	Inflammatory Myofibroblastic Tumor	Predictive	C	Supports Sensitivity Response
ROS1 Fusion1
Ceritinib	Lung Adenocarcinoma	Predictive	C	Supports Sensitivity Response	1	accepted	EID1248 Case report of a 77-year old male patient with lung adenocarcinoma (T2aN1M0, stage IIA) without EGFR, KRAS, or BRAF mutations, and no ALK gene rearrangement. CD72-ROS1 was identified in sequencing aft… (full text at CIViC) PMID 26917690 · Subbiah et al., 2016 · Open in CIViC	civic
ROS1 Fusion + ROS1 G2032R6
Crizotinib	Lung Adenocarcinoma	Predictive	C	Supports Resistance	4	accepted	EID1100 Resistance to crizotinib developed in a patient with metastatic lung adenocarcinoma harboring a CD74-ROS1 rearrangement who had initially shown a dramatic response to treatment. An acquired G2032R mut… (full text at CIViC) PMID 23724914 · Awad et al., 2013 · Open in CIViC	civic
Cabozantinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	accepted	EID1101 Cabozantinib was assessed in the CD74-ROS1-mutant Ba/F3 cells and crizotinib-resistant patient-derived cancer cells (MGH047) harboring G2032R-mutated CD74-ROS1. It effectively inhibited the survival o… (full text at CIViC) PMID 25351743 · Katayama et al., 2015 · Open in CIViC	civic
Crizotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER
ROS1 Fusion1
Crizotinib	Lung Adenocarcinoma	Predictive	C	Supports Sensitivity Response	3	accepted	EID1690 In an evaluation of a patient and never smoker with crizotinib-sensitive lung adenocarcinoma, an SDC4-ROS1 rearrangement was identified using comprehensive genomic profiling. The patient attained a de… (full text at CIViC) PMID 25922291 · Le et al., 2015 · Open in CIViC	civic
ROS1 G2032R1
Crizotinib	Lung Adenocarcinoma	Predictive	C	Supports Resistance	1	accepted	EID2934 Resistance to crizotinib developed in a patient with metastatic lung adenocarcinoma harboring a CD74-ROS1 rearrangement who had initially shown a dramatic response to treatment. A biopsy of a resistan… (full text at CIViC) PMID 23724914 · Awad et al., 2013 · Open in CIViC	civic
ROS1 G2032R + ROS1 Fusion1
DS-6501b	Lung Adenocarcinoma	Predictive	D	Supports Sensitivity Response	3	accepted	EID7538 In preclinical models, DS-6051b inhibited tumour growth and phospho-ROS1 levels in CD74-ROS1 G2032R mutant Ba/F3 cells. Similar results were seen in the crizotinib-resistant patient derived MGH047-4 c… (full text at CIViC) PMID 31399568 · Katayama et al., 2019 · Open in CIViC	civic
ROS1 Fusion + ROS1 L2026M4
Crizotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	2	accepted	EID1252 Preclinical study of PF-06463922 in NSCLC in-vitro, in-vivo and in enzyme assays. BaF3 cells expressing CD74-ROS1 L2026M were more resistant to crizotinib treatment than wildtype CD74-ROS1 in both cel… (full text at CIViC) PMID 25733882 · Zou et al., 2015 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	2	accepted	EID1257 Ba/F3 cells expressing CD74–ROS1 L2026M mutation showed resistance to crizotinib (~10 fold higher IC50 value), compared with those expressing wild-type CD74–ROS1; however, showed similar sensitivity t… (full text at CIViC) PMID 25688157 · Song et al., 2015 · Open in CIViC	civic
Foretinib	Lung Non-Small Cell Carcinoma
ROS1 Fusion + ROS1 G2101A2
Crizotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	2	accepted	EID1259 Ba/F3 cells expressing CD74–ROS1 G2101A showed resistance to crizotinib, compared with those expressing wild-type CD74–ROS1, and were sensitive to foretinib. PMID 25688157 · Song et al., 2015 · Open in CIViC	civic
Foretinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	2	accepted	EID1260 Ba/F3 cells expressing CD74–ROS1 G2101A showed resistance to crizotinib, compared with those expressing wild-type CD74–ROS1, and were sensitive to foretinib. PMID 25688157 · Song et al., 2015 · Open in CIViC	civic
ROS1 Fusion + ROS1 L2155S1
ALK Inhibitor TAE684 + Crizotinib + ForetinibSubstitutes	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	3	accepted	EID1256 The L2155S mutation in ROS1 was identified in the HCC78CR1, -2 and -3 cell lines which harbor the SLC34A2–ROS1 rearrangement and in 2 patients with NSCLC with progressive disease following crizotinib … (full text at CIViC) PMID 25688157 · Song et al., 2015 · Open in CIViC	civic
ROS1 G2032R + ROS1 Fusion1
Lorlatinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	accepted	EID1251 Preclinical study of PF-06463922 in NSCLC in-vitro, in-vivo and in enzyme assays. PF-06463922 showed inhibition of kinase activity, cell viability and tumor growth in wild-type, G2032R and L2026M muta… (full text at CIViC) PMID 25733882 · Zou et al., 2015 · Open in CIViC	civic
ALK Fusion + ROS1 FusionALK ROS11
Crizotinib	Malignant NeoplasmALIAS	Predictive	B	Supports Sensitivity Response	2	accepted	EID11671 This clinical study was conducted on patients harboring either ROS1 or ALK rearrangements, and were treated with Crizotinib. The two sub-protocols F(ALK rearrangements) and G(ROS1 rearrangements) had … (full text at CIViC) PMID 35233056 · Mansfield et al., 2022 · Open in CIViC	civic

Regulatory

Approvals mentioning the linked drugs (63)

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

1 record 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 (64)

Trials with an active ClinicalTrials.gov status, an intervention mapped to a derived drug and a condition mapped to an associated cancer. 24 recruiting · 17 active phase 3 · 172 in any status. Most recently updated first, 50 per page.

Computedrule biomarker-links-v1

clinicaltrialsPublishedShowing 51–64 of 64 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
NCT06082635	TGRX-326 Chinese Phase III for Advanced Non-small Cell Lung Cancer (NSCLC)	active not recruiting	Phase 3	321	Shenzhen TargetRx Co., Ltd.INDUSTRY	1	May 18, 2025	clinicaltrials
NCT06893354	Explore the Mechanisms Underlying Disease Resistance and Potential Primary Resistance Mechanism of Induction Therapy Lorlatinib in Resectable Non-small Cell Lung Cancer (NSCLC) Harboring ALK Positive Mutation Revealed by Single-cell RNA Sequencing and Spatial Transcriptomics	not yet recruiting	Phase 4	20	The First Affiliated Hospital of Guangzhou Medical UniversityOTHER	0	Mar 25, 2025	clinicaltrials
NCT06876675	LORLATINIB-related HYPERLIPIDEMIA in ALK+ Non-Small Cell Lung Cancer	enrolling by invitation	—	167	Peking University Third HospitalOTHER	1	Mar 14, 2025	clinicaltrials
NCT06858410	Lorlatinib Compared with Concurrent/ Sequential Chemoradiotherapy in Stage III ALK Positive Lung Adenocarcinoma	not yet recruiting	Phase 3	36	Guangdong Association of Clinical TrialsOTHER	0	Mar 5, 2025	clinicaltrials
NCT06694129	Real-world Observational Study of Targeted Therapy in Patients With Advanced ROS1-positive NSCLC	not yet recruiting	—	40	National Cancer Center, ChinaOTHER	0	Nov 19, 2024	clinicaltrials
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
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
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
NCT05859217	A Study of Combining Cabozantinib and Atezolizumab for Advanced/Metastatic NSCLC (Cabatezo-1)(Cabatezo-1)	not yet recruiting	Phase 2	40	Jun Zhang, MD, PhDOTHER	1	May 8, 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

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

Approval rows flagged tumor-agnostic (4)

Associated cancers (11)

Drugs with predictive evidence (10)

Predictive evidence items (35)

Approvals mentioning the linked drugs (63)

Active trials (64)

Linked publications (20)