Pembrolizumab is a programmed death receptor-1 (PD-1) blocking antibody indicated for:

Melanoma:

• Treatment of patients with unresectable or metastatic melanoma.
• Adjuvant treatment of melanoma with lymph node involvement after complete surgical resection.

Non-Small Cell Lung Cancer (NSCLC):

• In combination with pemetrexed and platinum chemotherapy for first-line treatment of metastatic non-squamous NSCLC without EGFR or ALK mutations.
• In combination with carboplatin and either paclitaxel or paclitaxel protein-bound for first-line treatment of metastatic squamous NSCLC.
• As a single agent for first-line treatment of metastatic NSCLC with PD-L1 expression (TPS ≥1%) without EGFR or ALK mutations.
• As a single agent for previously treated metastatic NSCLC with PD-L1 expression (TPS ≥1%).

Small Cell Lung Cancer (SCLC):

• Treatment of patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy and at least one additional therapy.

Head and Neck Squamous Cell Carcinoma (HNSCC):

• In combination with platinum and fluorouracil for first-line treatment of metastatic or unresectable recurrent HNSCC.
• As a single agent for first-line treatment of metastatic or unresectable recurrent HNSCC with PD-L1 expression.
• As a single agent for recurrent or metastatic HNSCC with disease progression after platinum-based therapy.

Classical Hodgkin Lymphoma (cHL):

• Treatment of adult and pediatric patients with refractory cHL or those who have relapsed after two or more lines of therapy.

Primary Mediastinal Large B-Cell Lymphoma (PMBCL):

• Treatment of adult and pediatric patients with refractory PMBCL or those who have relapsed after two or more prior therapies.

Urothelial Carcinoma:

• Treatment of locally advanced or metastatic urothelial carcinoma in patients not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1, or in patients not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.
• Treatment of patients with disease progression during or after platinum-based chemotherapy or within 12 months of neoadjuvant/adjuvant therapy.

Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Cancer: Treatment of adult and pediatric patients with unresectable or metastatic MSI-H or dMMR solid tumors that have progressed following prior treatment and have no satisfactory alternative options.

Gastric Cancer: Treatment of recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma with PD-L1 expression after two or more prior therapies.

Esophageal Cancer: Treatment of locally advanced or metastatic esophageal carcinoma with disease progression after prior therapy, with PD-L1 expression.

Cervical Cancer: Treatment of recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, with PD-L1 expression.

Hepatocellular Carcinoma (HCC): Treatment of patients previously treated with sorafenib.

Merkel Cell Carcinoma (MCC): Treatment of adult and pediatric patients with recurrent locally advanced or metastatic MCC.

Renal Cell Carcinoma (RCC): In combination with axitinib for first-line treatment of advanced RCC.

Endometrial Carcinoma: In combination with lenvatinib for advanced endometrial carcinoma not MSI-H or dMMR, after prior systemic therapy and not candidates for surgery or radiation.

Pembrolizumab is a programmed death receptor-1 (PD-1) blocking antibody. It is a humanized monoclonal IgG4 kappa antibody with an approximate molecular weight of 149 kDa, produced using recombinant Chinese hamster ovary (CHO) cells. Pembrolizumab for injection is available as a sterile, preservative-free, white to off-white lyophilized powder in single-dose vials intended for intravenous use. After reconstitution, each 2 mL solution contains 50 mg of pembrolizumab and includes L-histidine (3.1 mg), polysorbate 80 (0.4 mg), and sucrose (140 mg). Hydrochloric acid or sodium hydroxide may be added to adjust the pH to 5.5. Pembrolizumab injection is also supplied as a sterile, preservative-free, clear to slightly opalescent, colorless to pale yellow solution for intravenous use. Each vial contains 100 mg of pembrolizumab in 4 mL solution. Each 1 mL contains 25 mg of pembrolizumab and is formulated with L-histidine (1.55 mg), polysorbate 80 (0.2 mg), sucrose (70 mg), and Water for Injection, USP.

The binding of PD-1 ligands (PD-L1 and PD-L2) to the PD-1 receptor on T cells suppresses T-cell proliferation and cytokine production. Some tumors increase the expression of PD-1 ligands, allowing them to evade immune detection by inhibiting T-cell activity. Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2. This action releases the inhibition of the immune response mediated by the PD-1 pathway, thereby enhancing the body’s anti-tumor immune response. Preclinical studies in mouse tumor models have shown that inhibition of PD-1 activity leads to reduced tumor growth.

• Melanoma: 200 mg every 3 weeks
• NSCLC: 200 mg every 3 weeks
• SCLC: 200 mg every 3 weeks
• HNSCC: 200 mg every 3 weeks
• cHL or PMBCL: 200 mg every 3 weeks for adults; 2 mg/kg (up to 200 mg) every 3 weeks for pediatrics
• Urothelial Carcinoma: 200 mg every 3 weeks
• MSI-H Cancer: 200 mg every 3 weeks for adults and 2 mg/kg (up to 200 mg) every 3 weeks for pediatrics
• Gastric Cancer: 200 mg every 3 weeks
• Esophageal Cancer: 200 mg every 3 weeks
• Cervical Cancer: 200 mg every 3 weeks
• HCC: 200 mg every 3 weeks
• MCC: 200 mg every 3 weeks for adults; 2 mg/kg (up to 200 mg) every 3 weeks for pediatrics
• RCC: 200 mg every 3 weeks with axitinib 5 mg orally twice daily
• Endometrial Carcinoma: 200 mg every 3 weeks with lenvatinib 20 mg orally once daily for tumors that are not MSI-H or dMMR.

Administer Pembrolizumab as an intravenous infusion over 30 minutes.

None reported.

The most common adverse reactions (≥20%) include:

Pembrolizumab as a single agent: Fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, fever (pyrexia), cough, dyspnea, constipation, general pain, and abdominal pain.

Pembrolizumab with chemotherapy: Fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, fever, hair loss (alopecia), peripheral neuropathy, mucosal inflammation, and stomatitis.

Pembrolizumab with axitinib: Diarrhea, fatigue/asthenia, hypertension, liver toxicity (hepatotoxicity), hypothyroidism, decreased appetite, palmar-plantar erythrodysesthesia, nausea, stomatitis/mucosal inflammation, voice changes (dysphonia), rash, cough, and constipation.

Pembrolizumab with lenvatinib: Fatigue, hypertension, musculoskeletal pain, diarrhea, decreased appetite, hypothyroidism, nausea, stomatitis, vomiting, weight loss, abdominal pain, headache, constipation, urinary tract infection, dysphonia, bleeding events, hypomagnesemia, palmar-plantar erythrodysesthesia, dyspnea, cough, and rash.

Based on its mechanism of action, pembrolizumab may cause fetal harm when used during pregnancy. There are no adequate human data regarding embryo-fetal risk. It is not known whether pembrolizumab is present in human or animal milk or its effects on the breastfed infant. Due to the risk of serious adverse reactions, women should avoid breastfeeding during treatment and for at least 4 months after the last dose.

Immune-mediated pneumonitis: Withhold in moderate cases and permanently discontinue in severe, life-threatening, or recurrent cases.

Immune-mediated colitis: Withhold in moderate or severe cases and discontinue permanently if life-threatening.

Immune-mediated hepatitis and hepatotoxicity (with axitinib): Monitor liver function. Depending on severity, withhold or discontinue pembrolizumab and/or axitinib. Consider corticosteroid treatment.

Immune-mediated endocrinopathies:

• Adrenal insufficiency: Withhold in moderate cases and discontinue if severe or life-threatening.
• Hypophysitis: Withhold in moderate cases and discontinue if severe or life-threatening.
• Thyroid disorders: Monitor thyroid function; discontinue if severe hyperthyroidism occurs.
• Type 1 diabetes mellitus: Monitor blood glucose; withhold in severe hyperglycemia.

Immune-mediated nephritis: Monitor kidney function; withhold in moderate cases and discontinue if severe or life-threatening.

Immune-mediated skin reactions (including SJS/TEN): Withhold in severe cases and discontinue permanently if life-threatening.

Other immune-mediated reactions: In transplant patients, weigh benefits against the risk of organ rejection.

Infusion-related reactions: Stop infusion and discontinue permanently in severe or life-threatening cases.

Complications of allogeneic HSCT: After pembrolizumab: Monitor for GVHD, hepatic veno-occlusive disease, and other complications. Before pembrolizumab: Assess risk of GVHD in patients with prior transplant history.

Use of PD-1/PD-L1 inhibitors with thalidomide analogues and dexamethasone in multiple myeloma is not recommended outside clinical trials.

Embryo-fetal toxicity: May cause fetal harm. Use effective contraception during treatment.

Safety and effectiveness in pediatric patients have not been established. No significant differences in safety or efficacy have been observed between elderly and younger patients.

Immunological Chemotherapy, Immunosuppressant

Store vials refrigerated at 2°C to 8°C.