Pembrolizumab

Pembrolizumabis amonoclonal antibodyused to treat patients withunresectableor metastaticmelanomaanddiseaseprogression followingipilimumaband, if BRAF V600mutationpositive, a BRAF inhibitor. It is also used to treatnon-small cell lung cancer(NSCLC), head andnecksquamous cell carcinoma(HNSCC), classical HodgkinlymphomacHL), and urothelialcarcinoma(UC).

Pembrolizumab is available under the following different brand names:Keytruda.

Dosage Forms and Strengths

Lyophilized powder for reconstitution

• 50mg/瓶

Solution for injection

• 100 mg/4mL (25mg/mL)

Dosage Considerations – Should be Given as Follows:

Melanoma

• Indicated for unresectable or metastatic melanoma
• 2 mg/kg intravenously (IV) every 3 weeks until disease progression or unacceptabletoxicity
• InfuseIV over 30 minutes

Non-Small Cell Lung Cancer(NSCLC)

Also see Administration

Single-agent

• Indicated for the first-line treatment of patients with metastatic non-smallcelllung cancer(NSCLC) whose tumors have high PD-L1 expression [TumorProportion Score (TPS) 50% or greater)] as determined by anFDA-approved test, with noEGFRor ALKgenomictumor aberrations
• Also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1% or greater) as determined by an FDA-approved test, with disease progression on or after platinum-containingchemotherapy; patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approvedtherapyfor these aberrations prior to receiving pembrolizumab
• 200 mg intravenously (IV) every 3 weeks until disease progression or unacceptable toxicity, or up to 24 monthsinpatients without disease progression
• Select patients for treatment of metastatic NSCLC as a single agent based on the presence of positive PD-L1 expression
• Information on FDA-approved tests for detection of PD-L1 expression in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics

Combination therapy

• Indicated in combination with pemetrexed andcarboplatinfor first-line treatment of patients with metastatic nonsquamous NSCLC irrespective of PD-L1 expression
• When administering in combination with chemotherapy, administer pembrolizumab before chemotherapy
• Pembrolizumab 200 mg intravenously (IV) plus pemetrexed 500 mg/m² plus carboplatin (AUC 5 mg/mL/minute) IV on Day 1 of each 21-day cycle for 4 cycles, THEN
• Pembrolizumab 200 mg IV every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression

Head and Neck Squamous Cell Carcinoma (HNSCC)

Indicated for the treatment of patients withrecurrentor metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy

200 mg intravenously (IV) every 3 weeks infused over 30 minutes until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression

Dosing considerations (HNSCC)

• Indicationfor HNSCC approved under accelerated approval based on tumor response rate and durability of response
• Continued approval for this indication may be contingent upon verification and description ofclinicalbenefit in the confirmatory trials

Classical Hodgkin Lymphoma (cHL)

• Indicated for adult andpediatricpatients withrefractoryclassical Hodgkin lymphoma (cHL) or who have relapsed after 3 or more prior lines of therapy
• Adult: 200 mg intravenously (IV) every 3 weeks
• Pediatric: 2 mg/kg IV every 3wk; not to exceed 200 mg/dose
• Continue until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression
• Also see Administration

Urothelial Carcinoma

• Indicated for locally advanced or metastatic urothelial carcinoma (UC) in patients who are not eligible forcisplatin-containing chemotherapy; also indicated for patients with disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant oradjuvanttreatment with platinum-containing chemotherapy
• 200 mg intravenously (IV) every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression

Dosage Modifications

Permanently discontinue for any of the following

• Renalimpairment: No dosage adjustment required
• 温和的hepaticimpairment: No dosage adjustment required
• Moderate or severe hepatic impairment: Not studied
• Withhold for any of the following (may resume when recover to grade 0-1)
  • Grade 2 pneumonitis
  • Grade 2 or 3colitis
  • Grade 3 or 4 endocrinopathies (e.g., hypophysitis, hypo- or hyperthyroidism)
  • Grade 2nephritis
  • ASTorALTgreater than 3 and up to 5 times upper limit of normal (ULN) or totalbilirubingreater than 1.5 and up to 3 times ULN
  • Any other severe or grade 3 treatment-relatedadverse reaction
  • Any life-threatening adverse reaction (excluding endocrinopathies controlled withhormonereplacement therapy)
  • Grade 3 or 4 pneumonitis or recurrent pneumonitis of grade 2 severity
  • Grade 3 or 4 nephritis
  • AST or ALT greater than 5 times upper limit of normal (ULN) or total bilirubin greater than 3 times ULN
  • For patients withlivermetastasiswho begin treatment with grade 2 AST or ALT, discontinue if AST or ALT increases by 50% or greater relative tobaselineand lasts for at least 1 week
  • Grade 3 or 4 infusion-related reactions
  • Inability to reducecorticosteroiddose to up to 10 mg/day ofprednisoneor equivalent within 12 weeks
  • Persistent grade 2 or 3 adverse reactions that do not recover to grade 0-1 within 12 weeks after last dose of pembrolizumab
  • Any severe or grade 3 treatment-related adverse reaction that recurs

Dosing Considerations

Classical Hodgkin lymphoma (cHL), head and neck squamous cell carcinoma (HNSCC), and urothelial carcinoma (UC)

• Indication is approved under accelerated approval based on tumor response rate and durability of response
• Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials

Nonsquamous non-small cell lungcancer(NSCLC)

• Indication in for first-line treatment of patients with metastatic nonsquamous NSCLC in combination with pemetrexed and carboplatin was approved under accelerated approval based on tumor response rate and progression-free survival
• Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials

Common side effects of pembrolizumab include:

• Fatigue
• Anemia
• High blood sugar(hyperglycemia)
• Hyponatremia
• Hypoalbuminemia
• Nausea
• Cough
• Itching
• Rash
• Decreased appetite
• Hypertriglyceridemia
• 增加AST
• Constipation
• Diarrhea
• Jointpain
• Pain inextremity
• Shortness of breath
• Swelling of extremities
• Vomiting
• Headache
• Musclepain
• Chills
• Insomnia
• Abdominal pain
• Back pain
• Dizziness
• Fever
• Upperrespiratorytractinfection
• Loss ofskinpigmentation(vitiligo)
• Sepsis
• Immune-mediatedhypothyroidism
• Immune-mediated pneumonitis
• Immune-mediated hyperthyroidism
• Immune-mediated colitis

Less common side effects of pembrolizumab include:

• Immune-mediated nephritis
• Kidney(renal) failure
• Immune-mediatedhepatitis
• Immune-mediated hypophysitis

Postmarketing side effects of pembrolizumab reported include:

• Infusion-related reactions
• Exfoliativedermatitis
• Bullous pemphigoid
• Weakness/lack of energy
• Lymphopenia

This is not a complete list of side effects and other serious side effects may occur. Call yourdoctorfor information and medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

If your doctor has directed you to use thismedicationfor yourcondition, your doctor or药剂师may already be aware of any possible drug interactions or side effects and may be monitoring you for them. Do not start, stop, or change the dosage of this medicine or any medicine before getting further information from your doctor, healthcare provider or pharmacist first.

Pembrolizumab has no known severe interactions with other drugs.

Pembrolizumab has no known serious interactions with other drugs.

Pembrolizumab has no known moderate interactions with other drugs.

Pembrolizumab has no known mild interactions with other drugs.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with yourphysicianif you havehealthquestions or concerns.

Warnings

This medication contains pembrolizumab. Do not take Keytruda if you are allergic to pembrolizumab or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact aPoison Control Centerimmediately.

Contraindications

• None

Effects of Drug Abuse

• No information available

Short-Term Effects

• See "What Are Side Effects Associated with Using Pembrolizumab?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Pembrolizumab?"

Cautions

• Clinical trialsreported immune-mediated pneumonitis, colitis, hepatitis, nephritis and other immune-mediated adverse reactions (e.g.,uveitis,arthritis,myositis,pancreatitis,hemolytic anemia, partial seizures arising in apatientwith inflammatory foci inbrainparenchyma, myasthenicsyndrome,opticneuritis, andrhabdomyolysis).
• Severe dermatitis includingbullouspemphigoid and exfoliative dermatitis reported.
• Immune-mediated endocrinopathies: reported adrenal insufficiency, changes inthyroidfunction, and type 1diabetes mellitusincludingdiabetic ketoacidosis(withhold therapy in case of severe hyperglycemia untilmetaboliccontrolachieved).
• Infusion-related reactions, including severe and life-threatening reactions, reported; monitor patients for signs and symptoms of infusion-related reactions including rigors, chills,wheezing, itching, flushing, rash,low blood pressure(hypotension),hypoxemia, and fever; permanently discontinue therapy for severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions.
• Hypophysitis reported; monitor for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency); administer corticosteroids for Grade 2 or greater hypophysitis; withhold therapy for moderate (Grade 2) hypophysitis, withhold or discontinue for severe (Grade 3) hypophysitis, and permanently discontinue for life-threatening (Grade 4) hypophysitis.
• Thyroid disorders can occur; monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders.
• Administer corticosteroids for Grade 3 or greater hyperthyroidism; withhold treatment for severe (Grade 3) hyperthyroidism, and permanently discontinue for life-threatening (Grade 4) hyperthyroidism; isolated hypothyroidism may be managed with replacement therapy without treatment interruption and without corticosteroids.
• Renal failure reported.
• Embryofetal toxicity is likely, based on the drug's mechanism of action; women of reproductive potential should use highly effective contraception during treatment and for 4 months after the last dose.

Pregnancy and Lactation

• Use pembrolizumab duringpregnancyonly in LIFE-THREATENING emergencies when no safer drug is available. There is positive evidence of human fetal risk. Embryofetal toxicity is likely, based on the drug's mechanism of action.
• Women of reproductive potential should use highly effective contraception during treatment and for 4 months after the last dose.
• Animal models link the PD-1/PDL-1 signaling pathway with maintenance of pregnancy through induction ofmaternalimmune toleranceto fetaltissue. If pembrolizumab is used during pregnancy, or if the patient becomespregnantwhile taking pembrolizumab, apprise the patient of the potential hazard to afetus.
• It is unknown if pembrolizumab is distributed in humanbreast milk. It is not recommended for use whilebreastfeeding.