Drug Detail:Keytruda (Pembrolizumab [ pem-broe-liz-ue-mab ])
Generic Name: pembrolizumab 50mg in 2mL
Dosage Form: injection, powder, lyophilized, for solution
Drug Class: Anti-PD-1 and PD-L1 monoclonal antibodies (immune checkpoint inhibitors)
Patient Selection
Information on FDA-approved tests for patient selection is available at:
http://www.fda.gov/CompanionDiagnostics .
Patient Selection for Single-Agent Treatment
Select patients for treatment with KEYTRUDA as a single agent based on the presence of positive PD-L1 expression in:
- Stage III NSCLC who are not candidates for surgical resection or definitive chemoradiation [see Clinical Studies (14.2)].
- metastatic NSCLC [see Clinical Studies (14.2)].
- first-line treatment of metastatic or unresectable, recurrent HNSCC [see Clinical Studies (14.3)].
- previously treated recurrent locally advanced or metastatic esophageal cancer [see Clinical Studies (14.10)].
- recurrent or metastatic cervical cancer with disease progression on or after chemotherapy [see Clinical Studies (14.11)].
For the MSI-H/dMMR indications, select patients for treatment with KEYTRUDA as a single agent based on MSI-H/dMMR status in tumor specimens [see Clinical Studies (14.7, 14.8)].
For the TMB-H indication, select patients for treatment with KEYTRUDA as a single agent based on TMB-H status in tumor specimens [see Clinical Studies (14.16)].
Because subclonal dMMR mutations and microsatellite instability may arise in high-grade gliomas during temozolomide therapy, it is recommended to test for TMB-H, MSI-H, and dMMR in the primary tumor specimens obtained prior to initiation of temozolomide chemotherapy in patients with high-grade gliomas.
Additional Patient Selection Information for MSI-H or dMMR in Patients with non-CRC Solid Tumors
Due to discordance between local tests and FDA-approved tests, confirmation of MSI-H or dMMR status is recommended by an FDA-approved test in patients with MSI-H or dMMR solid tumors, if feasible. If unable to perform confirmatory MSI-H/dMMR testing, the presence of TMB ≥10 mut/Mb, as determined by an FDA-approved test, may be used to select patients for treatment [see Clinical Studies (14.7)].
Patient Selection for Combination Therapy
For use of KEYTRUDA in combination with chemotherapy, with or without bevacizumab, select patients based on the presence of positive PD-L1 expression in persistent, recurrent, or metastatic cervical cancer [see Clinical Studies (14.11)].
For the pMMR/not MSI-H advanced endometrial carcinoma indication, select patients for treatment with KEYTRUDA in combination with lenvatinib based on MSI or MMR status in tumor specimens [see Clinical Studies (14.15)].
For use of KEYTRUDA in combination with chemotherapy, select patients based on the presence of positive PD-L1 expression in locally recurrent unresectable or metastatic TNBC [see Clinical Studies (14.18)].
Additional Patient Selection Information
- An FDA-approved test for the detection of not MSI-H is currently unavailable for the selection of patients with not MSI-H endometrial carcinoma for treatment with KEYTRUDA in combination with lenvatinib [see Clinical Studies (14.15)].
Recommended Dosage
| Indication | Recommended Dosage of KEYTRUDA |
Duration/Timing of Treatment |
|---|---|---|
|
||
| Monotherapy | ||
| Adult patients with unresectable or metastatic melanoma |
200 mg every 3 weeks* or 400 mg every 6 weeks* |
Until disease progression or unacceptable toxicity |
| Adjuvant treatment of adult patients with melanoma, NSCLC, or RCC |
200 mg every 3 weeks* or 400 mg every 6 weeks* |
Until disease recurrence, unacceptable toxicity, or up to 12 months |
| Adult patients with NSCLC, HNSCC, cHL, PMBCL, locally advanced or metastatic Urothelial Carcinoma, MSI-H or dMMR Cancer, MSI-H or dMMR CRC, MSI-H or dMMR Endometrial Carcinoma, Esophageal Cancer, Cervical Cancer, HCC, MCC, TMB-H Cancer, or cSCC |
200 mg every 3 weeks* or 400 mg every 6 weeks* |
Until disease progression, unacceptable toxicity, or up to 24 months |
| Adult patients with high-risk BCG- unresponsive NMIBC |
200 mg every 3 weeks* or 400 mg every 6 weeks* |
Until persistent or recurrent high-risk NMIBC, disease progression, unacceptable toxicity, or up to 24 months |
| Pediatric patients with cHL, PMBCL, MSI-H or dMMR Cancer, MCC, or TMB- H Cancer |
2 mg/kg every 3 weeks (up to a maximum of 200 mg)* |
Until disease progression, unacceptable toxicity, or up to 24 months |
| Pediatric patients (12 years and older) for adjuvant treatment of melanoma |
2 mg/kg every 3 weeks (up to a maximum of 200 mg)* |
Until disease recurrence, unacceptable toxicity, or up to 12 months |
| Combination Therapy† | ||
| Adult patients with NSCLC, HNSCC, or Esophageal Cancer |
200 mg every 3 weeks* or 400 mg every 6 weeks* Administer KEYTRUDA prior to chemotherapy when given on the same day. |
Until disease progression, unacceptable toxicity, or up to 24 months |
| Adult patients with locally advanced or metastatic urothelial carcinoma |
200 mg every 3 weeks* or 400 mg every 6 weeks* Administer KEYTRUDA after enfortumab vedotin when given on the same day. |
Until disease progression, unacceptable toxicity, or up to 24 months |
| Adult patients with Gastric Cancer | 200 mg every 3 weeks* or 400 mg every 6 weeks* Administer KEYTRUDA prior to trastuzumab and chemotherapy when given on the same day. |
Until disease progression, unacceptable toxicity, or up to 24 months |
| Adult patients with Cervical Cancer | 200 mg every 3 weeks* or 400 mg every 6 weeks* Administer KEYTRUDA prior to chemotherapy with or without bevacizumab when given on the same day. |
Until disease progression, unacceptable toxicity, or for KEYTRUDA, up to 24 months |
| Adult patients with RCC | 200 mg every 3 weeks* or 400 mg every 6 weeks* Administer KEYTRUDA in combination with axitinib 5 mg orally twice daily‡ or Administer KEYTRUDA in combination with lenvatinib 20 mg orally once daily. |
Until disease progression, unacceptable toxicity, or for KEYTRUDA, up to 24 months |
| Adult patients with Endometrial Carcinoma |
200 mg every 3 weeks* or 400 mg every 6 weeks* Administer KEYTRUDA in combination with lenvatinib 20 mg orally once daily. |
Until disease progression, unacceptable toxicity, or for KEYTRUDA, up to 24 months |
| Adult patients with high-risk early-stage TNBC |
200 mg every 3 weeks* or 400 mg every 6 weeks* Administer KEYTRUDA prior to chemotherapy when given on the same day. |
Neoadjuvant treatment in combination with chemotherapy for 24 weeks (8 doses of 200 mg every 3 weeks or 4 doses of 400 mg every 6 weeks) or until disease progression or unacceptable toxicity, followed by adjuvant treatment with KEYTRUDA as a single agent for up to 27 weeks (9 doses of 200 mg every 3 weeks or 5 doses of 400 mg every 6 weeks) or until disease recurrence or unacceptable toxicity§ |
| Adult patients with locally recurrent unresectable or metastatic TNBC |
200 mg every 3 weeks* or 400 mg every 6 weeks* Administer KEYTRUDA prior to chemotherapy when given on the same day. |
Until disease progression, unacceptable toxicity, or up to 24 months |
Dose Modifications
No dose reduction for KEYTRUDA is recommended. In general, withhold KEYTRUDA for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue KEYTRUDA for Life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone or equivalent per day within 12 weeks of initiating steroids.
Dosage modifications for KEYTRUDA for adverse reactions that require management different from these general guidelines are summarized in Table 2.
| Adverse Reaction | Severity* | Dosage Modification |
|---|---|---|
| ALT = alanine aminotransferase, AST = aspartate aminotransferase, DRESS = Drug Rash with Eosinophilia and Systemic Symptoms, SJS = Stevens Johnson Syndrome, TEN = toxic epidermal necrolysis, ULN = upper limit normal | ||
|
||
| Immune-Mediated Adverse Reactions [see Warnings and Precautions (5.1)] | ||
| Pneumonitis | Grade 2 | Withhold† |
| Grade 3 or 4 | Permanently discontinue | |
| Colitis | Grade 2 or 3 | Withhold† |
| Grade 4 | Permanently discontinue | |
Hepatitis with no tumor involvement of the liver |
AST or ALT increases to more than 3 and up to 8 times ULN or Total bilirubin increases to more than 1.5 and up to 3 times ULN |
Withhold† |
| For liver enzyme elevations in patients treated with combination therapy with axitinib, see Table 3. |
AST or ALT increases to more than 8 times ULN or Total bilirubin increases to more than 3 times ULN |
Permanently discontinue |
| Hepatitis with tumor involvement of the liver‡ |
Baseline AST or ALT is more than 1 and up to 3 times ULN and increases to more than 5 and up to 10 times ULN or Baseline AST or ALT is more than 3 and up to 5 times ULN and increases to more than 8 and up to 10 times ULN |
Withhold† |
| ALT or AST increases to more than 10 times ULN or Total bilirubin increases to more than 3 times ULN |
Permanently discontinue | |
| Endocrinopathies | Grade 3 or 4 | Withhold until clinically stable or permanently discontinue depending on severity |
| Nephritis with Renal Dysfunction | Grade 2 or 3 increased blood creatinine | Withhold† |
| Grade 4 increased blood creatinine | Permanently discontinue | |
| Exfoliative Dermatologic Conditions | Suspected SJS, TEN, or DRESS | Withhold† |
| Confirmed SJS, TEN, or DRESS | Permanently discontinue | |
| Myocarditis | Grade 2, 3, or 4 | Permanently discontinue |
| Neurological Toxicities | Grade 2 | Withhold† |
| Grade 3 or 4 | Permanently discontinue | |
| Hematologic toxicity in patients with cHL or PMBCL |
Grade 4 | Withhold until resolution to Grades 0 or 1 |
| Other Adverse Reactions | ||
| Infusion-related reactions [see Warnings and Precautions (5.2)] |
Grade 1 or 2 | Interrupt or slow the rate of infusion |
| Grade 3 or 4 | Permanently discontinue | |
The following table represents dosage modifications that are different from those described above for KEYTRUDA or in the Full Prescribing Information for the drug administered in combination.
| Treatment | Adverse Reaction | Severity | Dosage Modification |
|---|---|---|---|
| ALT = alanine aminotransferase, AST = aspartate aminotransferase, ULN = upper limit normal | |||
|
|||
| KEYTRUDA in combination with axitinib |
Liver enzyme elevations* | ALT or AST increases to at least 3 times but less than 10 times ULN without concurrent total bilirubin at least 2 times ULN | Withhold both KEYTRUDA and axitinib until resolution to Grades 0 or 1† |
| ALT or AST increases to more than 3 times ULN with concurrent total bilirubin at least 2 times ULN or ALT or AST ≥10 times ULN |
Permanently discontinue both KEYTRUDA and axitinib |
||
Recommended Dose Modifications for Adverse Reactions for KEYTRUDA in Combination with Lenvatinib
When administering KEYTRUDA in combination with lenvatinib, modify the dosage of one or both drugs. Withhold or discontinue KEYTRUDA as shown in Table 2. Refer to lenvatinib prescribing information for additional dose modification information.
Preparation and Administration
Preparation for Intravenous Infusion
- Visually inspect the solution for particulate matter and discoloration. The solution is clear to slightly opalescent, colorless to slightly yellow. Discard the vial if visible particles are observed.
- Dilute KEYTRUDA injection (solution) prior to intravenous administration.
- Withdraw the required volume from the vial(s) of KEYTRUDA and transfer into an intravenous (IV) bag containing 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. Mix diluted solution by gentle inversion. Do not shake. The final concentration of the diluted solution should be between 1 mg/mL to 10 mg/mL.
- Discard any unused portion left in the vial.
Storage of Diluted Solution
The product does not contain a preservative.
Store the diluted solution from the KEYTRUDA 100 mg/4 mL vial either:
- At room temperature for no more than 6 hours from the time of dilution. This includes room temperature storage of the diluted solution, and the duration of infusion.
- Under refrigeration at 2°C to 8°C (36°F to 46°F) for no more than 96 hours from the time of dilution. If refrigerated, allow the diluted solution to come to room temperature prior to administration. Do not shake.
Discard after 6 hours at room temperature or after 96 hours under refrigeration.
Do not freeze.
