ALK TKI (3rd generation) · small molecule

lorlatinib

21 active trials across 6 of our biomarkers, targeting ALK/ROS1. 3 active approvals for a biomarker on marked.bio.

Also known as PF-06463922, Lorbrena, Lorviqua.

Counts only trials that select patients by one of the biomarkers on marked.bio, not every trial of this drug.

Approvals and pivotal results

Biomarker-selected approvals in the United States and the European Union, with the pivotal trial's results and side effects where we have them. Results from different trials are not directly comparable.

Therapy	Biomarker	Tumour	United States	European Union
lorlatinib FDA, 2018 metastatic, ALK-positive AA 02/11/2018 (after prior ALK TKIs), converted to regular approval 03/03/2021 with first-line use; current label: ALK-positive metastatic NSCLC. Source EU (EMA), 2019 ALK-positive advanced NSCLC progressed after alectinib or ceritinib as first ALK TKI, or after crizotinib and >=1 other ALK TKI Conditional MA 06/05/2019; conditional MA renewed 05/04/2024. EMA medicines data (Oct 2026) show conditional_approval = No and the EPAR page no longer carries the conditional flag, so the MA appears to have become standard after April 2024. The switch decision itself was not located; treat the type with caution. First-line indication added by II/0015 (EC 27/01/2022), now its own row. Source EU (EMA), 2022 ALK-positive advanced NSCLC not previously treated with an ALK inhibitor II/0015, EC decision 27/01/2022. approval_type: see A072 (switch from conditional not located). Source Lorbrena, Lorviqua	ALK fusion	NSCLC	Approved 2018	Approved 2019
In the US label CROWN vs crizotinib, 149 vs 147 patients PFS not reached vs 9.3 months, HR 0.28 (0.19-0.41)Response 76% vs 58% Serious side effects 34%Stopped for side effects 6.7%Fatal 3.4% Trial details and side effects Patients first-line ALK-positive NSCLC (NCT03052608) Most common side effects oedema 56%, weight gain 38%, peripheral neuropathy 34%, cognitive effects 21%, diarrhoea 21% (149 patients) Later trial Brain metastases: response in the brain 82% vs 23% (17 vs 13 patients with measurable lesions). Notes US label rev. 01/2026. Source US label In the EU product information B7461001 single-arm, 99 (one prior ALK TKI); 111 (two or more) Response 42% (one prior TKI); 40% (two or more) (33-53; 31-49)Lasting not reached; 9.9 months Trial details and side effects Patients ALK-positive NSCLC after at least one ALK inhibitor (NCT01970865) Notes EU SmPC section 5.1 (previously treated cohorts). Source EU product information In the EU product information CROWN vs crizotinib, 149 vs 147 patients PFS not reached vs 9 months, HR 0.28 (0.19-0.41)Response 76% vs 58%OS HR 0.72 (0.41-1.25), immature Trial details and side effects Patients first-line ALK-positive NSCLC (NCT03052608) Most common side effects oedema 56%, weight gain 38%, peripheral neuropathy 34%, cognitive effects 21%, diarrhoea 21% (149 patients) Later trial Brain metastases: response in the brain 82% vs 23% (17 vs 13 patients with measurable lesions). Notes EU SmPC section 5.1 (CROWN). Side effects from the US label. Source EU product information

Biomarkers

Biomarker	Active trials	All trials	Furthest active phase
ALK fusion	19	32	Phase 4
ROS1 fusion	4	8	Phase 4
BRAF V600E	0	1	–
EGFR exon 19 deletion / L858R	0	1	–
KRAS G12C	0	1	–
KRAS G12D	0	1	–

Trials

21 of 36 trials shown

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 The First Affiliated Hospital of Guangzhou Medical University Started 2025Primary completion 2027-07 NCT06893354

lorlatinib FDA EU

Documented ALK-fusion positive（ Ventana , assessed by a local laboratory）

ALK fusionNSCLC
Lorlatinib in Patients With ALK-Positive NSCLC With Brain or Leptomeningeal Metastases

Active, not recruiting Phase 4 Guangdong Association of Clinical Trials Started 2024Primary completion 2026-04 NCT06282874

lorlatinib FDA EU

Histologically or cytologically confirmed ALK-positive NSCLC.

ALK fusionCarcinoma, Non-Small-Cell Lung, Brain Metastases, Leptomeningeal Metastasis
Lorlatinib Continuation Study

Active, not recruiting Phase 4 Pfizer Started 2021Primary completion 2029-10 NCT05144997

lorlatinib FDA EU

…CONTINUATION PROTOCOL: AN OPEN-LABEL, SINGLE-ARM CONTINUATION STUDY FOR PARTICIPANTS WITH ALK-POSITIVE OR ROS1-POSITIVE NON-SMALL CELL LUNG CANCER (NSCLC) CONTINUING FROM PFIZER SPONSORED LORL…

ALK fusionROS1 fusionNon-Small-Cell Lung Cancer, NSCLC
Lorlatinib Compared with Concurrent/ Sequential Chemoradiotherapy in Stage III ALK Positive Lung Adenocarcinoma

Not yet recruiting Phase 3 Guangdong Association of Clinical Trials Started 2025Primary completion 2030-03 NCT06858410

lorlatinib FDA EU

Study Population: Patients with histologically or cytologically confirmed diagnosis of ALK-positive, lung adenocarcinoma who present with locally advanced, unresectable (Stage III) disease …

ALK fusionNeoadjuvant Non-Small Cell Lung Cancer
Testing the Addition of 131I-MIBG or Lorlatinib to Intensive Therapy in People With High-Risk Neuroblastoma (NBL)

Recruiting Phase 3 Children's Oncology Group Started 2018Primary completion 2030-09 NCT03126916

BusulfancarboplatincisplatincyclophosphamideDexrazoxane HydrochlorideDinutuximabdoxorubicinetoposideIsotretinoinlorlatinib FDA EUmelphalanSargramostim

PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH …

ALK fusionGanglioneuroblastoma, Ganglioneuroblastoma, Nodular, Neuroblastoma
A Study Of Lorlatinib Versus Crizotinib In First Line Treatment Of Patients With ALK-Positive NSCLC

Active, not recruiting Phase 3 Pfizer Started 2017Primary completion 2020-03 NCT03052608

lorlatinib FDA EUcrizotinib FDA EU

Histologically or cytologically confirmed diagnosis of locally advanced or metastatic ALK-positive NSCLC

ALK fusionCarcinoma, Non-Small-Cell Lung
Lorlatinib Plus Local Consolidation Therapy In ALK Positive Advanced Non-Small Cell Lung Cancer

Recruiting Phase 2 M.D. Anderson Cancer Center Started 2026Primary completion 2028-07 NCT07415005

lorlatinib FDA EU

Lorlatinib Plus Local Consolidation Therapy In ALK Positive Advanced Non-Small Cell Lung Cancer

ALK fusionAdvanced Non-Small Cell Lung Cancer
Lorlatinib Plus Sacituzumab Tirumotecan With Peripheral ctDNA Guidance as First-Line Therapy for ALK Fusion-Positive NSCLC

Not yet recruiting Phase 2 Guangdong Association of Clinical Trials Started 2026Primary completion 2029-09 NCT07750704

lorlatinib FDA EUsacituzumab tirumotecan

Confirmation of ALK fusion by tumor histology, cytology, or blood-based testing;

ALK fusionALK Positive Non-small Cell Lung Cancer
Lorlatinib in ROS1+ NSCLC With Brain Metastasis

Not yet recruiting Phase 2 Hunan Cancer Hospital Started 2025Primary completion 2027-01 NCT07083687

lorlatinib

Histologically or cytologically confirmed diagnosis of ROS1+ NSCLC with brain metastases before the use of lorlatinib.

ROS1 fusionLung Cancer (NSCLC)
Lorlatinib as Neoadjuvant Treatment in Stage IB-IIIB ALK-rearranged Non-Small Cell Lung Cancer

Not yet recruiting Phase 2 Peking University People's Hospital Started 2024Primary completion 2026-04 NCT06682884

lorlatinib FDA EU

Documented ALK-rearrangement mutation positive (assessed by a local laboratory)

ALK fusionNeoadjuvant Non-Small Cell Lung Cancer
A Study to Evaluate the Combination of Platinum-pemetrexed Based Chemotherapy Plus Lorlatinib in ALK Positive Non-Small Cell Lung Cancer (NSCLC) With Exclusively Extracranial Disease Progression on Lorlatinib

Recruiting Phase 2 Centro di Riferimento Oncologico - Aviano Started 2024Primary completion 2028-05 NCT06378892

lorlatinib FDA EU

Histologically or cytologically confirmed diagnosis of stage IV ALK positive NSCLC.

ALK fusionStatus may be outdated, last updated 2024-04-23Non Small Cell Lung Cancer Metastatic, ALK Gene Mutation
Lorlatinib as the First-line Treatment in China Advanced ALK+ NSCLC

Recruiting Phase 2 Guangdong Association of Clinical Trials Started 2023Primary completion 2025-08 NCT06092086

lorlatinib FDA EU

Diagnosed as ALK-positive NSCLC as in CC cohort, but not fulfilled CC cohort inclusion criteria 2\~9 as above menti…

ALK fusionStatus may be outdated, last updated 2023-10-23ALK Positive Non-small Cell Lung Cancer
Induction Lorlatinib in Stage III Non-small Cell Lung Cancer

Active, not recruiting Phase 2 Guangdong Provincial People's Hospital Started 2023Primary completion 2025-12 NCT05740943

lorlatinib FDA EU

Pathologically confirmed diagnosis with Stage III NSCLC which harbored ALK fusion detected by next generation sequencing (NGS) or immunohistochemistry (IHC) with or withou…

ALK fusionStage III NSCLC, Surgery
A Study of Lorlatinib in Combination With Ramucirumab in People With Lung Cancer

Active, not recruiting Phase 1/2 Memorial Sloan Kettering Cancer Center Started 2023Primary completion 2028-08 NCT06007937

lorlatinib FDA EUramucirumab

ALK fusion identified by next generation sequencing (NGS) or IHC on material obtained from tumor or …

ALK fusionNon Small Cell Lung Cancer, Metastatic, Recurrent
ALK Tyrosine Kinase Inhibitors in ALK-rearranged Advanced Squamous Cell Carcinoma

Recruiting Phase 2 Hunan Province Tumor Hospital Started 2021Primary completion 2026-06 NCT05014464

crizotinib FDA EUalectinib FDA EUbrigatinib FDA EUlorlatinib FDA EUpemetrexedcarboplatinpaclitaxel

ALK fusion positive evaluated by IHC (ventana), NGS or FISH.

ALK fusionStatus may be outdated, last updated 2024-09-20Non-small Cell Lung Cancer
Lorlatinib After Failure of First-line TKI in Patients With Advanced ROS1-positive NSCLC (ALBATROS)

Active, not recruiting Phase 2 Intergroupe Francophone de Cancerologie Thoracique Started 2021Primary completion 2025-02 NCT04621188

lorlatinib

…(Stage IIIB, IIIC or IV accordingly to 8th classification TNM, UICC 2015) that carries an ROS1 rearrangement, as determined by the molecular biology platform of the investigator by FISH assay or by …

ROS1 fusionNon Small Cell Lung Cancer Metastatic
Activity of Lorlatinib Based on ALK Resistance Mutations Detected on Blood in ALK Positive NSCLC Patients

Active, not recruiting Phase 2 European Organisation for Research and Treatment of Cancer - EORTC Started 2020Primary completion 2024-07 NCT04127110

lorlatinib FDA EU

Histologically or cytologically confirmed diagnosis of NSCLC with ALK rearrangement, assessed by fluorescence in situ hybridization (FISH) assay (Abbott Molecular Inc) or by…

ALK fusionNon Small Cell Lung Cancer
Study of NXP900 With Lorlatinib in ALK+ Lung Cancer

Recruiting Phase 1 Nuvectis Pharma Started 2026Primary completion 2027-08 NCT07784959

NXP900lorlatinib FDA EU

Unresectable, metastatic or locally advanced ALK-positive NSCLC.

ALK fusionALK Positive, ALK Positive Non-small Cell Lung Cancer, NSCLC, ALK+ Non-Small-Cell Lung Carcinoma
AQUA07 in Patients With ALK-Positive Non-Small Cell Lung Cancer

Recruiting Phase 1 Roche Started 2026Primary completion 2030-08 NCT07617337

AQUA07lorlatinib FDA EU

…xcluding sputum cytology) proven diagnosis of locally advanced unresectable or metastatic ALK-positive NSCLC, who have experienced disease progression during or following their most recent sys…

ALK fusionALK Positive Non-small Cell Lung Cancer
Lorlatinib for Newly-Diagnosed High-Grade Glioma With ROS or ALK Fusion

Recruiting Early Phase 1 Nationwide Children's Hospital Started 2025Primary completion 2029-07 NCT06333899

lorlatinib FDA EU

Lorlatinib for Newly-Diagnosed High-Grade Glioma With ROS or ALK Fusion

ALK fusionROS1 fusionHigh Grade Glioma, Diffuse Intrinsic Pontine Glioma, Anaplastic Astrocytoma, Infant Type Hemispheric Glioma
Analysis of the Effectiveness and Safety of Lorlatinib in Untreated ALK-Positive NSCLC Patients in a French Real-World Context

Recruiting No phase Pfizer Started 2025Primary completion 2028-11 NCT06487078

lorlatinib FDA EU

…ologically confirmed diagnosis of locally advanced or metastatic (TNM 8th classification) ALK-positive NSCLC (IHC 3+/FISH positive/transcriptomic method)

ALK fusionALK+ Non-Small-Cell Lung Carcinoma
Lorlatinib in ALK Inhibitor Treated Unresectable Advanced/Recurrent ALK-Positive Non Small Cell Lung Cancer Patients in India

Completed Phase 4 Pfizer Started 2020 NCT04541706

lorlatinib FDA EU

…cally confirmed diagnosis of unresectable advanced and/or recurrent NSCLC that carries an ALK rearrangement, as detected by an appropriate test.

ALK fusionAdvanced Non-Small Cell Lung Cancer
Study of Lorlatinib In People With ALK-positive Non-small Cell Lung Cancer

Completed Phase 4 Pfizer Started 2020 NCT04362072

lorlatinib FDA EU

…static NSCLC (Stage IV, American Joint Committee on Cancer \[AJCC\] v7.0) that carries an ALK rearrangement.

ALK fusionCarcinoma, Non-Small-Cell Lung
Lorlatinib in Combination With Chemotherapy in Participants With Metastatic Anaplastic Lymphoma Kinase Positive (ALK+) Non-small Cell Lung Cancer (NSCLC) Who Progressed on Single-agent Lorlatinib

Withdrawn Phase 2 SCRI Development Innovations Started 2023 NCT05948462

lorlatinib FDA EUcisplatincarboplatinpemetrexed

Metastatic ALK+ NSCLC

ALK fusionLung Cancer, Non-small Cell Lung Cancer
Lorlatinib After Failure of First-line Second-generation ALK Kinase Inhibitor in Patients With Advanced ALK-positive Non-small Cell Lung Cancer

Completed Phase 2 Intergroupe Francophone de Cancerologie Thoracique Started 2020 NCT04111705

lorlatinib FDA EU

…NSCLC (Stage IIIB or IV accordingly to 8th classification TNM, UICC 2015) that carries an ALK rearrangement, as determined by the molecular biology platform of the investigator by FISH assay or by …

ALK fusionNon Small Cell Lung Cancer Metastatic
Lorlatinib Combinations in Lung Cancer

Unknown status Phase 1/2 Massachusetts General Hospital Started 2020 NCT04292119

lorlatinib FDA EUcrizotinib FDA EUbinimetinibbatoprotafib

A Phase IB/II Study of Lorlatinib Combinations in Anaplastic Lymphoma Kinase-Rearranged Lung Cancer

ALK fusionLung Cancer, Anaplastic Lymphoma Kinase Gene Translocation, ROS1 Rearrangement, Relapsed Cancer
A Study of Oral Lorlatinib in Patients With Relapsed ALK Positive Lymphoma

Completed Phase 2 University of Milano Bicocca Started 2019 NCT03505554

lorlatinib FDA EU

ALK+ Lymphoma diagnosed by IHC or FISH.

ALK fusionAnaplastic Large Cell Lymphoma, ALK-Positive
Targeted Treatment for ALK Positive Patients Who Have Previously Been Treated for Non-squamous Non-small Cell Lung Cancer

Terminated Phase 2 National Cancer Institute (NCI) Started 2019 NCT03737994

alectinib FDA EUbrigatinib FDA EUcarboplatinceritinib FDA EUcisplatincrizotinib FDA EUensartinib FDAlorlatinib FDA EUpemetrexed

Patients must have histologically or cytologically confirmed stage IV ALK-positive non-squamous non-small cell lung carcinoma (NSCLC) (includes M1a, M1b, M1c stage disease,…

ALK fusionLung Non-Squamous Non-Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8
A Study of Lorlatinib in ALK Inhibitor-Treated ALK-Positive NSCLC in China

Completed Phase 2 Pfizer Started 2019 NCT03909971

lorlatinib FDA EU

… (Roche Diagnostics), the Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular), or the EML4 ALK Fusion Gene Detection Kit (AmoyDx).

ALK fusionCarcinoma, Non-Small-Cell Lung
Study of Lorlatinib in ROS1 Rearranged NSCLC

Unknown status Phase 2 National Cancer Center, Korea Started 2019 NCT03612154

lorlatinib

Metastatic or recurrent NSCLC with ROS1 rearrangement identified by NGS-based target sequencing

ROS1 fusionNonsmall Cell Lung Cancer
PF-06463922 for Crizotinib Pretreated ROS1 Positive Non-small-cell Lung Cancer

Unknown status Phase 2 Fondazione Ricerca Traslazionale Started 2017 NCT03439215

lorlatinib

Histologically/cytologically confirmed diagnosis of NSCLC with evidence of ROS1 rearrangement;

ROS1 fusionCarcinoma, Non-Small-Cell Lung
A Study of Lorlatinib in Advanced ALK and ROS1 Rearranged Lung Cancer With CNS Metastasis in the Absence of Measurable Extracranial Lesions

Unknown status Phase 2 Massachusetts General Hospital Started 2016 NCT02927340

lorlatinib FDA EU

…s of metastatic NSCLC (Stage IV, American Joint Committee on Cancer v7.0) that carries an ALK rearrangement, as determined by the Food and Drug Administration (FDA)-approved FISH test, using Vysis®…

ALK fusionROS1 fusionNon-Small Cell Lung Cancer (NSCLC)
A Study Of PF-06463922 An ALK/ROS1 Inhibitor In Patients With Advanced Non Small Cell Lung Cancer With Specific Molecular Alterations

Completed Phase 1/2 Pfizer Started 2014 NCT01970865

lorlatinib FDA EUcrizotinib FDA EU

…tologically confirmed diagnosis of metastatic NSCLC (Stage IV, AJCC v7.0) that carries an ALK rearrangement, as determined by the Food and Drug Administration (FDA) approved FISH assay (Abbott Mole…

ALK fusionROS1 fusionALK-positive Non Small Cell Lung Cancer (NSCLC) and ROS1-positive NSCLC
PF-07284892 in Participants With Advanced Solid Tumors

Terminated Phase 1 Pfizer Started 2021 NCT04800822

PF-07284892lorlatinibbinimetinibcetuximabencorafenib

…or cytological diagnosis of ALK-positive advanced NSCLC, CRC with BRAF V600E mutation, or RAS- mutant, NF1-mutant or BRAF class 3 mutant solid tumor.

KRAS G12CKRAS G12DBRAF V600EALK fusionSolid Tumor
Temodar Plus Tyrosine Kinase Inhibitors for Progressive CNS Disease

Completed Phase 1 University of Colorado, Denver Started 2020 NCT04541407

temozolomideosimertinib FDA EUlorlatinib

…e in the CNS on osimertinib 80 mg daily for patients with EGFR activating mutations (EGFR exon 19 deletions or EGFR L858R exon 21 point mutations) -OR- Stage IV NSCLC with progression of disease i…

EGFR exon 19 deletion / L858RALK fusionNon Small Cell Lung Cancer, CNS Progression
NANT 2015-02: A Phase 1 Study of Lorlatinib (PF-06463922)

Completed Phase 1 New Approaches to Neuroblastoma Therapy Consortium Started 2017 NCT03107988

lorlatinib FDA EUcyclophosphamidetopotecanpegfilgrastim

1\) Patients are required to have an activating ALK aberration in their tumor detected by certified assay (i.e.

ALK fusionNeuroblastoma

Approvals and pivotal results

Biomarkers

Sponsors

Trials