Pembrolizumab

Patients who are cisplatin-eligible Cisplatin ineligibility is defined as meeting at least one of the following criteria: Creatinine clearance of less than 60 mL/min, ECOG PS 2 or higher, Grade 2 or higher hearing loss, NYHA Class III or higher heart failure, or Grade 2 or higher peripheral neuropathy. Neoadjuvant: Administer KEYTRUDA 200 mg every 3 weeks for 4 doses or 400 mg every 6 weeks for 2 doses in combination with enfortumab vedotin-ejfv or until disease progression that precludes curative-intent cystectomy or unacceptable toxicity Adjuvant: Administer KEYTRUDA 200 mg every 3 weeks for 13 doses or 400 mg every 6 weeks for 7 doses in combination with enfortumab vedotin-ejfv or until disease recurrence or unacceptable toxicity Patients who are cisplatin-ineligible : Neoadjuvant: Administer KEYTRUDA 200 mg every 3 weeks for 3 doses in combination with enfortumab vedotin or until disease progression that precludes curative-intent cystectomy or unacceptable toxicity.

Recommended Dosage Administer KEYTRUDA as a 30-minute intravenous infusion. The recommended dosages of KEYTRUDA are presented in Table 1. [See table below.] 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 Refer to the Prescribing Information for the agents administered in combination with KEYTRUDA for recommended dosing information, as appropriate.

Adult patients with resectable NSCLC 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 12 weeks or until disease progression that precludes definitive surgery or unacceptable toxicity, followed by adjuvant treatment with KEYTRUDA as a single agent after surgery for 39 weeks or until disease recurrence or unacceptable toxicity Adult patients with NSCLC, MPM, HNSCC, HER2-negative Gastric Cancer, Esophageal Cancer, or BTC 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 cancer 200 mg every 3 weeks or 400 mg every 6 weeks Administer KEYTRUDA after enfortumab vedotin-ejfv when given on the same day. Until disease progression, unacceptable toxicity, or up to 24 months Adult patients with MIBC 200 mg every 3 weeks or 400 mg every 6 weeks Administer KEYTRUDA after enfortumab vedotin-ejfv when given on the same day.

Patients who are cisplatin-eligible Cisplatin ineligibility is defined as meeting at least one of the following criteria: Creatinine clearance of less than 60 mL/min, ECOG PS 2 or higher, Grade 2 or higher hearing loss, NYHA Class III or higher heart failure, or Grade 2 or higher peripheral neuropathy. Neoadjuvant: Administer KEYTRUDA 200 mg every 3 weeks for 4 doses or 400 mg every 6 weeks for 2 doses in combination with enfortumab vedotin-ejfv or until disease progression that precludes curative-intent cystectomy or unacceptable toxicity Adjuvant: Administer KEYTRUDA 200 mg every 3 weeks for 13 doses or 400 mg every 6 weeks for 7 doses in combination with enfortumab vedotin-ejfv or until disease recurrence or unacceptable toxicity Patients who are cisplatin-ineligible : Neoadjuvant: Administer KEYTRUDA 200 mg every 3 weeks for 3 doses in combination with enfortumab vedotin or until disease progression that precludes curative-intent cystectomy or unacceptable toxicity.

Adjuvant: Administer KEYTRUDA 200 mg every 3 weeks for 14 doses or 400 mg every 6 weeks for 7 doses in combination with enfortumab vedotin or until disease recurrence or unacceptable toxicity Adult patients with locally advanced HNSCC 200 mg every 3 weeks or 400 mg every 6 weeks Administer KEYTRUDA prior to cisplatin when given on the same day.

Neoadjuvant: Administer KEYTRUDA for 6 weeks or until disease progression that precludes definitive surgery or unacceptable toxicity. Adjuvant: Administer KEYTRUDA in combination with RT with or without cisplatin. Continue KEYTRUDA as a single agent. Continue KEYTRUDA until disease recurrence or unacceptable toxicity or up to one year Adult patients with HER2-positive 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 chemoradiotherapy or 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 When axitinib is used in combination with KEYTRUDA, dose escalation of axitinib above the initial 5 mg dose may be considered at intervals of six weeks or longer. 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 prior to carboplatin and paclitaxel when given on the same day. 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 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 Patients who experience disease progression or unacceptable toxicity related to KEYTRUDA with neoadjuvant treatment in combination with chemotherapy should not receive adjuvant single agent KEYTRUDA.

Adult patients with unresectable locally advanced or metastatic TNBC 200 mg every 3 weeks or 400 mg every 6 weeks Until disease progression, unacceptable toxicity, or up to 24 months 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 Adult patients with Ovarian Cancer 200 mg every 3 weeks or 400 mg every 6 weeks Administer KEYTRUDA prior to paclitaxel with or without bevacizumab when given on the same day. Until disease progression, unacceptable toxicity, or up to 24 months Adjuvant treatment of adult patients with ccRCC 200 mg every 3 weeks or 400 mg every 6 weeks Administer KEYTRUDA in combination with belzutifan 120 mg orally once daily.

Until disease recurrence, unacceptable toxicity, or up to 12 months

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 (temperatures at or below 25°C) 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. Administration Administer diluted solution intravenously over 30 minutes through an intravenous line containing a sterile, non-pyrogenic, low-protein binding 0.2 micron to 5 micron in-line or add-on filter.

Do not co-administer other drugs through the same infusion line.