pembrolizumab

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Associated Genetic Biomarkers

Associated Diseases

Overview

Generic Name(s):

lambrolizumab

Trade Name(s):

Keytruda

NCI Definition [1]:

A humanized monoclonal immunoglobulin (Ig) G4 antibody directed against human cell surface receptor PD-1 (programmed death-1 or programmed cell death-1) with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, pembrolizumab binds to PD-1, an inhibitory signaling receptor expressed on the surface of activated T cells, and blocks the binding to and activation of PD-1 by its ligands, which results in the activation of T-cell-mediated immune responses against tumor cells. The ligands for PD-1 include programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs. Activated PD-1 negatively regulates T-cell activation and plays a key role in in tumor evasion from host immunity.

Biomarker-Directed Therapies

Pembrolizumab can be used in the treatment of non-small cell lung carcinoma, malignant solid tumor, adenocarcinoma of the gastroesophageal junction, breast carcinoma, and cervical carcinoma. PD-L1 Expression, PD-L1 High Expression, and PD-L1 Low Expression are the most frequent biomarker inclusion criteria for use of pembrolizumab [2].

Breast Carcinoma +

Disease is predicted to be sensitive to pembrolizumab: -

Biomarker Criteria:

Sample must match all of the following:

Sample must match one or more of the following:

PD-L1 Expression

Sample must match one or more of the following:

Triple-Negative Breast Cancer Alterations

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

Note: Indicated in combination with chemotherapy for patients with locally recurrent, unresectable, or metastatic TNBC whose tumors express PD-L1 [Combined Positive Score (CPS) >= 10].

Biomarker Criteria: Sample must match all of the following: Sample must match one or more of the following: PD-L1 Expression Sample must match one or more of the following: Triple-Negative Breast Cancer Alterations	Clinical Setting(s): Metastatic (FDA, NCCN)
	Note: Indicated in combination with chemotherapy for patients with locally recurrent, unresectable, or metastatic TNBC whose tumors express PD-L1 [Combined Positive Score (CPS) >= 10].

Cervical Carcinoma +

Colorectal Carcinoma +

Disease is predicted to be sensitive to pembrolizumab: -

Biomarker Criteria:

Sample must match all of the following:

MSI-High/dMMR

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

Note: Approved for unresectable or metastatic, microsatellite instability-high or mismatch repair deficient colorectal cancer, for first line treatment or after progression following a fluoropyrimidine, oxaliplatin, and irinotecan.

Biomarker Criteria: Sample must match all of the following: MSI-High/dMMR	Clinical Setting(s): Metastatic (FDA, NCCN)
	Note: Approved for unresectable or metastatic, microsatellite instability-high or mismatch repair deficient colorectal cancer, for first line treatment or after progression following a fluoropyrimidine, oxaliplatin, and irinotecan.

Gastric Carcinoma +

Disease is predicted to be sensitive to pembrolizumab: -

Biomarker Criteria:

Sample must match one or more of the following:

PD-L1 Expression

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

Note: Approved for recurrent locally advanced or metastatic tumors expresssing PD-L1 [Combined Positive Score (CPS) >=1] with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy.

Biomarker Criteria: Sample must match one or more of the following: PD-L1 Expression	Clinical Setting(s): Metastatic (FDA, NCCN)
	Note: Approved for recurrent locally advanced or metastatic tumors expresssing PD-L1 [Combined Positive Score (CPS) >=1] with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy.

Head And Neck Squamous Cell Carcinoma +

Malignant Esophageal Neoplasm +

Disease is predicted to be sensitive to pembrolizumab: -

Biomarker Criteria:

Sample must match all of the following:

PD-L1 Expression

Clinical Setting(s): Metastatic (NCCN)

Note: Recommended for recurrent locally advanced or metastatic tumors expresssing PD-L1 [Combined Positive Score (CPS) >=1] with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy.

Biomarker Criteria: Sample must match all of the following: PD-L1 Expression	Clinical Setting(s): Metastatic (NCCN)
	Note: Recommended for recurrent locally advanced or metastatic tumors expresssing PD-L1 [Combined Positive Score (CPS) >=1] with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy.

Malignant Solid Tumor +

Disease is predicted to be sensitive to pembrolizumab: -

Biomarker Criteria:

Sample must match one or more of the following:

TMB-High

Clinical Setting(s): Metastatic (FDA)

Note: Indicated for unresectable or metastatic tumor mutational burden-high [≥10 mutations/megabase] solid tumors with progression following prior treatment and no satisfactory alternative treatment options.

Biomarker Criteria: Sample must match one or more of the following: TMB-High	Clinical Setting(s): Metastatic (FDA)
	Note: Indicated for unresectable or metastatic tumor mutational burden-high [≥10 mutations/megabase] solid tumors with progression following prior treatment and no satisfactory alternative treatment options.

Biomarker Criteria:

Sample must match all of the following:

MSI-High/dMMR

Clinical Setting(s): Metastatic (FDA)

Note: FDA-approved for adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options.

Biomarker Criteria: Sample must match all of the following: MSI-High/dMMR	Clinical Setting(s): Metastatic (FDA)
	Note: FDA-approved for adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options.

Non-Small Cell Lung Carcinoma +

Disease is predicted to be sensitive to pembrolizumab: -

Biomarker Criteria:

Sample must match all of the following:

PD-L1 Low Expression

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

Note: For low expression of PD-L1 (Tumor Proportion Score >= 1% and <50%, clone 22C3) in the absence of EGFR & ALK (FDA/NCCN) and ROS1, RET, BRAF V600E, and MET Exon 14 Skipping (NCCN) mutations: recommended as a single agent for first-line therapy (for patients with contraindications to combination chemotherapy, per NCCN), or as subsequent line with disease progression during or following appropriate systemic chemotherapy.

Biomarker Criteria:

Sample must match all of the following:

PD-L1 Low Expression

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

Biomarker Criteria:

Sample must match all of the following:

PD-L1 High Expression

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

Note: For high expression of PD-L1 (Tumor Proportion Score >= 50%, clone 22C3) in the absence of EGFR & ALK (FDA/NCCN) and ROS1, RET, BRAF V600E, and MET Exon 14 Skipping (NCCN) mutations: recommended as a single agent for first-line therapy, or as subsequent line with disease progression during or following appropriate systemic chemotherapy.

Biomarker Criteria: Sample must match all of the following: PD-L1 High Expression	Clinical Setting(s): Metastatic (FDA, NCCN, ASCO)
	Note: For high expression of PD-L1 (Tumor Proportion Score >= 50%, clone 22C3) in the absence of EGFR & ALK (FDA/NCCN) and ROS1, RET, BRAF V600E, and MET Exon 14 Skipping (NCCN) mutations: recommended as a single agent for first-line therapy, or as subsequent line with disease progression during or following appropriate systemic chemotherapy.

Biomarker Criteria:

Sample must match all of the following:

Sample must match one or more of the following:

PD-L1 High Expression, PD-L1 Low Expression

Sample must match one or more of the following:

ALK Fusion, EGFR A763_Y764insFQEA, EGFR Exon 19 Deletion, EGFR Exon 19 Insertion, EGFR G719A, EGFR G719C, EGFR G719S, EGFR L858R, EGFR L861Q, EGFR S768I, EGFR T790M

Clinical Setting(s): Metastatic (FDA)

Note: For PD-L1 expressing tumors (Tumor Proportion Score >=1%, clone 22C3) with an EGFR or ALK alteration: FDA-approved as subsequent line of therapy following targeted therapy. However, per NCCN, data in the second-line setting suggest that subsequent pembrolizumab monotherapy is less effective in tumors with an EGFR mutation or ALK rearrangement.

Biomarker Criteria: Sample must match all of the following: Sample must match one or more of the following: PD-L1 High Expression, PD-L1 Low Expression Sample must match one or more of the following: ALK Fusion, EGFR A763_Y764insFQEA, EGFR Exon 19 Deletion, EGFR Exon 19 Insertion, EGFR G719A, EGFR G719C, EGFR G719S, EGFR L858R, EGFR L861Q, EGFR S768I, EGFR T790M	Clinical Setting(s): Metastatic (FDA)
	Note: For PD-L1 expressing tumors (Tumor Proportion Score >=1%, clone 22C3) with an EGFR or ALK alteration: FDA-approved as subsequent line of therapy following targeted therapy. However, per NCCN, data in the second-line setting suggest that subsequent pembrolizumab monotherapy is less effective in tumors with an EGFR mutation or ALK rearrangement.

Biomarker Criteria:

Sample must match all of the following:

Sample must match one or more of the following:

PD-L1 High Expression, PD-L1 Low Expression

Sample must match one or more of the following:

BRAF V600E, RET Fusion, ROS1 Fusion, MET Exon 14 Skipping

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

Note: For PD-L1 expressing tumors (Tumor Proportion Score >=1%, clone 22C3) with a ROS1, RET, BRAF V600E, or MET Exon 14 Skipping alteration: approved as a single agent for first- or subsequent-line therapy. However, per NCCN, targeted therapy for the oncogenic driver should take precedence over an immune checkpoint inhibitor.

Biomarker Criteria: Sample must match all of the following: Sample must match one or more of the following: PD-L1 High Expression, PD-L1 Low Expression Sample must match one or more of the following: BRAF V600E, RET Fusion, ROS1 Fusion, MET Exon 14 Skipping	Clinical Setting(s): Metastatic (FDA, NCCN)
	Note: For PD-L1 expressing tumors (Tumor Proportion Score >=1%, clone 22C3) with a ROS1, RET, BRAF V600E, or MET Exon 14 Skipping alteration: approved as a single agent for first- or subsequent-line therapy. However, per NCCN, targeted therapy for the oncogenic driver should take precedence over an immune checkpoint inhibitor.

Biomarker Criteria:

Sample must match one or more of the following:

PD-L1 High Expression, PD-L1 Low Expression

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

Note: Pembrolizumab is indicated as subsequent therapy for patients with NSCLC expressing CD274 (programmed death ligand 1 (PD-L1)), and whose disease has progressed on or after platinum-containing chemotherapy. An improved overall response rate was observed in CD274 (PD-L1) positive tumors.

Biomarker Criteria: Sample must match one or more of the following: PD-L1 High Expression, PD-L1 Low Expression	Clinical Setting(s): Second Line of Therapy (NICE, SMC)
	Note: Pembrolizumab is indicated as subsequent therapy for patients with NSCLC expressing CD274 (programmed death ligand 1 (PD-L1)), and whose disease has progressed on or after platinum-containing chemotherapy. An improved overall response rate was observed in CD274 (PD-L1) positive tumors.

Clinical Trials

View Clinical Trials for pembrolizumab

Pembrolizumab has been investigated in 921 clinical trials, of which 812 are open and 109 are closed. Of the trials investigating pembrolizumab, 18 are early phase 1 (15 open), 201 are phase 1 (175 open), 170 are phase 1/phase 2 (144 open), 440 are phase 2 (393 open), 3 are phase 2/phase 3 (3 open), 79 are phase 3 (73 open), 3 are phase 4 (2 open), and 7 are no phase specified (7 open).

HER2 Deficient Expression, HER2 Negative, and ER Negative are the most frequent biomarker inclusion criteria for pembrolizumab clinical trials.

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

Top Biomarker Inclusion Criteria for Open Clinical Trials Investigating Pembrolizumab

Top Biomarker Inclusion Criteria for Closed Clinical Trials Investigating Pembrolizumab

This graph displays the 20 most frequently occurring biomarkers curated on clinical trials investigating pembrolizumab and the cancer types associated with these biomarkers. These numbers are derived from a set of 5,956 clinical trials for which biomarker status defines treatment.

Drug Details

Synonyms [2]:

sch 900475, mk-3475, lambrolizumab, Keytruda, immunoglobulin g4, anti-(human programmed cell death 1); humanized mouse monoclonal (228-l-proline(h10-s>p))gamma 4 heavy chain (134-218')-disulfide with humanized mouse monoclonal kappa light chain dimer (226-226'':229-229'')-bisdisulfide

Drug Categories [2]:

Anti-PD-1 antibodies, Immunotherapies, Therapeutic antibodies

Drug Target(s) [2]:

PDCD1

NCIT ID [1]:

C106432

SNOMED ID [1]:

R-FF88F

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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