Drug · Small Molecule

Lorlatinib

CI-DRUG-00000349Explore in graph →NCIt C113655 CHEMBL3286830 CIViC Approved

Regulatory

Approvals (5)

Each record names the authority, jurisdiction, indication text and status. A drug approved in one jurisdiction for one indication is not 'approved' in general.

emaRegulatory1 approval record · authority, jurisdiction and indication text as published.

Jurisdiction · authority	Cancer	Indication	Status	Approval date	Source
EU EMA	Lung Non-Small Cell Carcinoma	Lorviqua as monotherapy is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)?positive advanced non?small cell lung cancer (NSCLC) previously not treated with an ALK inhibitor. Lorviqua as monotherapy is indicated for the treatment of adult patients with ALK?positive advanced NSCLC whose disease has progressed after: alectinib or ceritinib as the first ALK tyrosine kinase inhibitor (TKI) therapy; or crizotinib and at least one other ALK TKI.	approved	May 6, 2019

Health Canada records are DIN-level: one row per marketed product (brand, strength, form). The Drug Product Database does not publish indications, so no cancer is stated for these rows, and a cancelled or dormant DIN is the status of that one product — not a withdrawal of the molecule.

Data updated 16 hours agoSource updated unknown

Derived

Development pipeline

Most advanced stage across all cancers, then per top-level cancer reached through trial conditions or approval indications. Approval in any ingested jurisdiction outranks trial phase; counts are interventional studies.

Scope	Stage	Max phase	Active	Recruiting	Phase 3	Trials	Approvals	Jurisdictions	First approval	First trial
All cancers	Approved	Phase 4	21	8	3	40	5	CA, EU, US	Nov 2, 2018	Jan 8, 2014
Malignant Lung Neoplasm	Approved	Phase 4	13	3	2	23	1	EU	May 6, 2019	Jan 8, 2014
Non-Hodgkin Lymphoma	Phase2	Phase 2	0	0	0	2	0	—	—	Sep 28, 2019
Malignant Central Nervous System Neoplasm	Phase1	Early Phase 1	1	1	0	1

Curated evidence

Clinical evidence (28)

CIViC items in which this therapy appears, grouped by cancer context, then molecular profile. 50 items per page.

civicCuratedShowing 1–28 of 28 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 e7::e351
Lorlatinib	Glioblastoma

Clinical trials

Trials with this intervention (56)

Most recently updated first, 50 per page.

clinicaltrialsPublishedShowing 51–56 of 56 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
NCT03612154	Study of Lorlatinib in ROS1 Rearranged NSCLC	unknown	Phase 2	35	National Cancer Center, KoreaOTHER_GOV	1	Apr 6, 2022	clinicaltrials
NCT03439215	PF-06463922 for Crizotinib Pretreated ROS1 Positive Non-small-cell Lung Cancer(PFROST)	unknown	Phase 2

Molecule

Record

Kind: Small Molecule
Mechanism: ALK tyrosine kinase receptor inhibitor; EML4-ALK inhibitor
Targets: 2 genes
UNII: OSP71S83EU
Aliases: 2H-4,8-Methenopyrazolo(4,3-H)(2,5,11)benzoxadiazacyclotetradecine-3-carbonitrile, 7-amino-12-fluoro-10,15,16,17-tetrahydro-2,10,16-trimethyl-15-oxo-, (10R)-, 7-Amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo(4,3-h)(2,5,11)benzoxadiazacyclotetradecine-3-carbonitrile, Lorbrena, LORBRENA, Lorlatinib, Lorviqua, PF 06463922, PF-06463922, PF06463922

Data updated 19 hours agoSource updated unknown

Identifiers

Codes (6)

Upstream identifiers kept as first-class codes; each links to its registry where a stable public URL exists.

System	Code	Label
ATC (WHO)	L01ED05	LORLATINIB
DIN (Health Canada)	02485966

ALK Fusion5
Lorlatinib	Inflammatory Myofibroblastic Tumor	Predictive	C	Supports Sensitivity Response	4	submitted	EID11294 This case study was on an 18-year-old Caucasian female presenting with severe headaches. Brain MRI revealed multiple brain masses with the largest (5 cm) found in the anterior left frontal lobe. A met… (full text at CIViC) PMID 28713152 · Yuan et al., 2017 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	4	submitted	EID11191 In a phase 3 trial (CROWN, NCT03052608), a comparison of the selective third generation ALK inhibitor lorlatinib to the first generation ALK inhibitor crizotinib in 296 untreated ALK-fusion positive… (full text at CIViC) PMID 33207094 · Shaw et al., 2020 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	4	accepted	EID7286 In a phase 2 trial, patients with NSCLC with ALK fusion received lorlatinib. In treatment-naive patients, ORR was 90.0% In patients with at least one previous ALK tyrosine kinase inhibitor, ORR were a… (full text at CIViC) PMID 30413378 · Solomon et al., 2018 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	4	submitted	EID7590 A phase 2 trial of 228 ALK-positive NSCLC with or without previous chemotherapy treatment found lorlatinib to be effective in ALK inhibitor treatment-naive NSCLC as well as following treatment with on… (full text at CIViC) PMID 30413378 · Solomon et al., 2018 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	4	submitted	EID11192 In a post hoc analysis of the phase 3 trial (CROWN, NCT03052608) comparing the selective third generation ALK inhibitor lorlatinib to the first generation ALK inhibitor crizotinib in ALK-fusion posit… (full text at CIViC) PMID 35605188 · Solomon et al., 2022 · Open in CIViC	civic

ALK C1156Y + ALK Fusion2
Lorlatinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	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
Alectinib + Brigatinib + Ceritinib + LorlatinibSubstitutes	Malignant NeoplasmALIAS	Predictive	D	Does Not Support Resistance	4	submitted	EID7609 In vitro experiments showed that cells expressing EML4-ALK with the resistance mutation C1156Y were sensitive to second and third generation ALK inhibitors. In cell survival assays Ba/F3 cells with C1… (full text at CIViC) PMID 26698910 · Shaw et al., 2016 · Open in CIViC	civic

ALK G1202R + ALK L1196M + ALK Fusion2
Lorlatinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	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
Alectinib + Brigatinib + Ceritinib + Crizotinib + LorlatinibSubstitutes	Malignant NeoplasmALIAS	Predictive	D	Supports Resistance	4	submitted	EID7592 EML4-ALK expressing Ba/F3 cell lines with the compound ALK mutation G1202R/L1196M were found to be resistant to lorlatinib as well as first and second-line ALK inhibitors. H3122 lung cancer cell lines… (full text at CIViC) PMID 29650534 · Yoda et al., 2018 · Open in CIViC	civic