crizotinib

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Associated Genetic Biomarkers

Associated Diseases

Overview

Trade Name(s):

Xalkori

NCI Definition [1]:

An orally available aminopyridine-based inhibitor of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK) and the c-Met/hepatocyte growth factor receptor (HGFR) with antineoplastic activity. Crizotinib, in an ATP-competitive manner, binds to and inhibits ALK kinase and ALK fusion proteins. In addition, crizotinib inhibits c-Met kinase, and disrupts the c-Met signaling pathway. Altogether, this agent inhibits tumor cell growth. ALK belongs to the insulin receptor superfamily and plays an important role in nervous system development. ALK dysregulation and gene rearrangements are associated with a series of tumors.

Biomarker-Directed Therapies

Crizotinib can be used in the treatment of non-small cell lung carcinoma, anaplastic large cell lymphoma, and inflammatory myofibroblastic tumor. ALK, ALK Fusion, and MET are the most frequent biomarker inclusion criteria for use of crizotinib [2].

Anaplastic Large Cell Lymphoma +

Inflammatory Myofibroblastic Tumor +

Non-Small Cell Lung Carcinoma +

Disease is predicted to be sensitive to crizotinib: -

Biomarker Criteria:

Sample must match all of the following:

ALK Fusion

Clinical Setting(s): Metastatic (FDA, NCCN, ASCO)

Note: Approved by FDA for patients with ALK-positive or ROS1-positive metastatic NSCLC.

Biomarker Criteria: Sample must match all of the following: ALK Fusion	Clinical Setting(s): Metastatic (FDA, NCCN, ASCO)
	Note: Approved by FDA for patients with ALK-positive or ROS1-positive metastatic NSCLC.

Biomarker Criteria:

Sample must match all of the following:

ROS1 Fusion

Clinical Setting(s): Metastatic (FDA, NCCN, ASCO)

Note: Approved by FDA for patients with ALK-positive or ROS1-positive metastatic NSCLC. Recommended by NCCN as a preferred agent for first-line therapy.

Biomarker Criteria: Sample must match all of the following: ROS1 Fusion	Clinical Setting(s): Metastatic (FDA, NCCN, ASCO)
	Note: Approved by FDA for patients with ALK-positive or ROS1-positive metastatic NSCLC. Recommended by NCCN as a preferred agent for first-line therapy.

Biomarker Criteria:

Sample must match one or more of the following:

MET Amplification, MET Exon 14 Skipping

Clinical Setting(s): Metastatic (NCCN)

Note: Recommended by NCCN under Category 2A for patients with high-level MET amplification or MET exon 14 skipping mutations.

Biomarker Criteria: Sample must match one or more of the following: MET Amplification, MET Exon 14 Skipping	Clinical Setting(s): Metastatic (NCCN)
	Note: Recommended by NCCN under Category 2A for patients with high-level MET amplification or MET exon 14 skipping mutations.

Biomarker Criteria:

Sample must match all of the following:

ALK Fusion

Clinical Setting(s): First Line of Therapy (NICE, SMC), Second Line of Therapy (NICE, SMC)

Note: Approved by FDA for patients with ALK-positive or ROS1-positive metastatic NSCLC.

Biomarker Criteria: Sample must match all of the following: ALK Fusion	Clinical Setting(s): First Line of Therapy (NICE, SMC), Second Line of Therapy (NICE, SMC)
	Note: Approved by FDA for patients with ALK-positive or ROS1-positive metastatic NSCLC.

Disease is predicted to be resistant to crizotinib: -

Biomarker Criteria:

Sample must match all of the following:

ROS1 Fusion

Sample must match one or more of the following:

ROS1 D2033N, ROS1 G2032R

Clinical Setting(s): Metastatic (MCG)

Note: ROS1 D2033N and ROS1 G2032R have been identified as resistance mutations in patients treated with crizotinib. For more information, see Gainor, J., et al., 2017 (PMID: 29333528).

Biomarker Criteria: Sample must match all of the following: Sample must match all of the following: ROS1 Fusion Sample must match one or more of the following: ROS1 D2033N, ROS1 G2032R	Clinical Setting(s): Metastatic (MCG)
	Note: ROS1 D2033N and ROS1 G2032R have been identified as resistance mutations in patients treated with crizotinib. For more information, see Gainor, J., et al., 2017 (PMID: 29333528).

Biomarker Criteria:

Sample must match all of the following:

Sample must match one or more of the following:

ALK F1174C, ALK F1174V, ALK G1202del

ALK Mutations in Lung Cancer

Sample must match all of the following:

ALK Fusion

Clinical Setting(s): Metastatic (MCG)

Note: Secondary mutations associated with ALK TKI therapy may arise in the kinase domain, leading to acquired resistance.

Biomarker Criteria: Sample must match all of the following: Sample must match one or more of the following: ALK F1174C, ALK F1174V, ALK G1202del ALK Mutations in Lung Cancer Sample must match all of the following: ALK Fusion	Clinical Setting(s): Metastatic (MCG)
	Note: Secondary mutations associated with ALK TKI therapy may arise in the kinase domain, leading to acquired resistance.

Biomarker Criteria:

Sample must match all of the following:

Sample must match one or more of the following:

ALK Mutations in Lung Cancer

Sample must match all of the following:

ALK Fusion

Clinical Setting(s): Metastatic (BNF)

Note: Secondary mutations associated with ALK TKI therapy may arise in the kinase domain, leading to acquired resistance.

Biomarker Criteria: Sample must match all of the following: Sample must match one or more of the following: ALK Mutations in Lung Cancer Sample must match all of the following: ALK Fusion	Clinical Setting(s): Metastatic (BNF)
	Note: Secondary mutations associated with ALK TKI therapy may arise in the kinase domain, leading to acquired resistance.

Clinical Trials

View Clinical Trials for crizotinib

Crizotinib has been investigated in 26 clinical trials, of which 23 are open and 3 are closed. Of the trials investigating crizotinib, 4 are phase 1 (2 open), 3 are phase 1/phase 2 (3 open), 13 are phase 2 (12 open), 5 are phase 3 (5 open), and 1 is no phase specified (1 open).

ALK Fusion, MET Amplification, and ROS1 Fusion are the most frequent biomarker inclusion criteria for crizotinib clinical trials.

Non-small cell lung carcinoma, malignant solid tumor, and lymphoma are the most common diseases being investigated in crizotinib clinical trials [2].

Top Biomarker Inclusion Criteria for Open Clinical Trials Investigating Crizotinib

Top Biomarker Inclusion Criteria for Closed Clinical Trials Investigating Crizotinib

This graph displays the 20 most frequently occurring biomarkers curated on clinical trials investigating crizotinib and the cancer types associated with these biomarkers. These numbers are derived from a set of 5,931 clinical trials for which biomarker status defines treatment.

Drug Details

Synonyms [2]:

met tyrosine kinase inhibitor pf-02341066, 3-[(1r)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)-1h-pyrazol-4- yl)pyridin-2-amine, 2-pyridinamine, 3-[(1r)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(4-piperidinyl)-1h- pyrazol-4-yl], Xalkori, pf-02341066, pf-2341066

Drug Categories [2]:

ALK inhibitors, ROS1 inhibitors, Tyrosine kinase inhibitors

Drug Target(s) [2]:

ALK, MET, MST1R, ROS1

NCIT ID [1]:

C74061

SNOMED ID [1]:

R-FBD1D

References

1. National Cancer Institute. NCI Thesaurus Version 18.11d. https://ncit.nci.nih.gov/ncitbrowser/. [2018-07-30] [2018-08-02].

2. All assertions and clinical trial landscape data are curated from primary sources. You can read more about the curation process here.

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Associated Genetic Biomarkers

Associated Diseases

Overview

Biomarker-Directed Therapies

Clinical Trials

Drug Details

References

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