Pembromax

Description

Pembrolizumab is a programmed death receptor-1 (PD 1)-blocking antibody. Pembrolizumab is a humanized monoclonal IgG4 kappa antibody with an approximate molecular weight of 149 kDa. Pembrolizumab is produced in recombinant Chinese hamster ovary (CHO) cells. Pembrolizumab for injection is a sterile, preservative-free, white to off-white lyophilized powder in single-dose vials for intravenous use. Each 2 mL of reconstituted solution contains 50 mg of pembrolizumab and is formulated in L-histidine (3.1 mg), polysorbate 80 (0.4 mg), and sucrose (140 mg). May contain hydrochloric acid/sodium hydroxide to adjust pH to 5.5. Pembrolizumab injection is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution for intravenous use. Each vial contains 100 mg of pembrolizumab in 4 mL of solution. Each 1 mL of solution contains 25 mg of pembrolizumab and is formulated in: L-histidine (1.55 mg), polysorbate 80 (0.2 mg), sucrose (70 mg), and Water for Injection, USP.

Pharmacology
Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth.
Dosage & Administration
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.

Contraindications
None.

Side Effects
Most common adverse reactions (reported in ≥20% of patients) were:

Pembrolizumab as a single agent: fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain.

Pembrolizumab in combination with chemotherapy: fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, pyrexia, alopecia, peripheral neuropathy, mucosal inflammation, and stomatitis.

Pembrolizumab in combination with axitinib: diarrhea, fatigue/asthenia, hypertension, hepatotoxicity, hypothyroidism, decreased appetite, palmar-plantar erythrodysesthesia, nausea, stomatitis/mucosal inflammation, dysphonia, rash, cough, and constipation.

Pembrolizumab in combination with lenvatinib: fatigue, hypertension, musculoskeletal pain, diarrhea, decreased appetite, hypothyroidism, nausea, stomatitis, vomiting, decreased weight, abdominal pain, headache, constipation, urinary tract infection, dysphonia, hemorrhagic events, hypomagnesemia, palmar-plantar erythrodysesthesia, dyspnea, cough, and rash.
Pregnancy & Lactation
Based on its mechanism of action, Pembrolizumab can cause fetal harm when administered to a pregnant woman. There are no available human data informing the risk of embryo-fetal toxicity. There are no data on the presence of pembrolizumab in either animal or human milk or its effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with Pembrolizumab and for 4 months after the final dose.
Precautions & Warnings
Immune-mediated pneumonitis: Withhold for moderate, and permanently discontinue for severe, life-threatening or recurrent moderate pneumonitis.

Immune-mediated colitis: Withhold for moderate or severe, and permanently discontinue for life-threatening colitis.

Immune-mediated hepatitis (Pembrolizumab) and hepatotoxicity (Pembrolizumab in combination with axitinib): Monitor for changes in hepatic function. Based on severity of liver enzyme elevations, withhold or discontinue Pembrolizumab, axitinib, or Pembrolizumab and axitinib. Consider corticosteroid therapy.

Immune-mediated endocrinopathies:
Adrenal insufficiency: Withhold for moderate and withhold or permanently discontinue for severe or life-threatening adrenal insufficiency.
Hypophysitis: Withhold for moderate and withhold or permanently discontinue for severe or life-threatening hypophysitis.
Thyroid disorders: Monitor for changes in thyroid function. Withhold or permanently discontinue for severe or life-threatening hyperthyroidism.
Type 1 diabetes mellitus: Monitor for hyperglycemia. Withhold Pembrolizumab in cases of severe hyperglycemia.
Immune-mediated nephritis: Monitor for changes in renal function. Withhold for moderate, and permanently discontinue for severe or life-threatening nephritis.

Immune-mediated skin adverse reactions including, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN): Withhold for severe and permanently discontinue for life-threatening skin reactions.

Other immune-mediated adverse reactions: In organ transplant recipients, consider the benefit of treatment with Pembrolizumab versus the risk of possible organ rejection.

Infusion-related reactions: Stop infusion and permanently discontinue Pembrolizumab for severe or life-threatening infusion reactions.

Complications of allogeneic HSCT: Allogeneic HSCT after treatment with Pembrolizumab: Monitor for hepatic veno-occlusive disease, grade 3-4 acute GVHD including hyperacute GVHD, steroid-requiring febrile syndrome, and other immune-mediated adverse reactions. Transplant-related mortality has occurred. Allogeneic HSCT prior to treatment with Pembrolizumab: In patients with a history of allogeneic HSCT, consider the benefit of treatment with Pembrolizumab versus the risk of GVHD.

Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials.

Embryo-Fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective method of contraception.
Use in Special Populations
The safety and effectiveness of Pembrolizumab in pediatric patients have not been established. No overall differences in safety or effectiveness were observed between elderly patients and younger patients.

Therapeutic Class
Immunological Chemotherapy, Immunosuppressant

Storage Conditions
Store vials under refrigeration at 2°C to 8°C.