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.

openfdaRegulatory2 approval records · authority, jurisdiction and indication text as published.

Jurisdiction · authority	Cancer	Indication	Status	Approval date	Source
US FDA	—	Efficacy supplement 2021-03-03 (see label)	approved	Mar 3, 2021	openfda
US FDA	—	LORBRENA ® is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. LORBRENA is a kinase inhibitor indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. ( 1 , 2.1 )

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 14 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 17 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