Penpulimab-kcqx (Monograph)

Brand name: Penpulimab-kcqx
Drug class: Antineoplastic Agents

Introduction

Penpulimab-kcqx, a programmed death receptor-1 (PD-1)-blocking antibody, is an antineoplastic agent.¹

Uses for Penpulimab-kcqx

Penpulimab-kcqx has the following uses:

Penpulimab-kcqx is used in combination with either cisplatin or carboplatin and gemcitabine for the first-line treatment of adults with recurrent or metastatic non-keratinizing nasopharyngeal carcinoma (NPC).¹

Penpulimab-kcqx is also used as a single agent for the treatment of adults with metastatic non-keratinizing NPC with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy.¹

Penpulimab-kcqx Dosage and Administration

General

Penpulimab-kcqx is available in the following dosage form(s) and strength(s):

Injection: 100 mg/10 mL (10 mg/mL) solution in a single-dose vial for dilution prior to administration.¹

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

• Administer as an IV infusion after dilution.¹ See Full Prescribing Information for additional preparation and administration instructions.¹

• Recommended dosage of penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine: 200 mg IV over 60 minutes every 3 weeks until disease progression or unacceptable toxicity, for a maximum of 24 months.¹ See Full Prescribing Information for order of administration and dosage recommendations for gemcitabine, cisplatin, and carboplatin.¹

• Recommended dosage of penpulimab-kcqx as a single agent:200 mg IV over 60 minutes every 2 weeks until disease progression or unacceptable toxicity, for a maximum of 24 months.¹

• See Full Prescribing Information for dosage modification recommendations for adverse reactions.¹

Cautions for Penpulimab-kcqx

Contraindications

None.¹

Warnings/Precautions

Severe and Fatal Immune-Mediated Adverse Reactions

Penpulimab-kcqx is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death-receptor 1 (PD-1) or the PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions.¹ Important immune-mediated adverse reactions described in the prescribing information may not include all possible severe and fatal immune-mediated reactions.¹

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue and can affect more than one body system simultaneously.¹ Immune-mediated adverse reactions can occur at any time after starting treatment with a PD-1/PD- L1 blocking antibody.¹ While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of PD-1/PD-L1 blocking antibodies.¹ Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies.¹ Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions.¹ Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment.¹ In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection.¹ Institute medical management promptly, including specialty consultation as appropriate.¹ Withhold or permanently discontinue penpulimab-kcqx depending on severity.¹ In general, if penpulimab-kcqx requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less.¹ Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month.¹ Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.¹

Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.¹

Immune-Mediated Pneumonitis: Penpulimab-kcqx can cause immune-mediated pneumonitis.¹ In patients treated with other PD-1/PD-L1 blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation.¹ Immune-mediated pneumonitis occurred in 0.7% (1/146) of patients receiving penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine, which was a Grade 2 (0.7%) adverse reaction.¹ Systemic corticosteroids were required in the patient.¹ Pneumonitis led to withholding of penpulimab-kcqx in the patient.¹ When used as a single agent, immune-mediated pneumonitis occurred in 1.3% (5/372) of patients receiving penpulimab-kcqx, including Grade 3 (0.5%), Grade 2 (0.5%) and Grade 1 (0.3%) adverse reactions.¹ Systemic corticosteroids were required in 80% (4/5) of patients with pneumonitis.¹ Pneumonitis led to permanent discontinuation of penpulimab-kcqx in 0.8% (3/372).¹ Pneumonitis resolved in 20% (1/5) of these patients.¹

Immune-Mediated Colitis: Penpulimab-kcqx can cause immune-mediated colitis, which may present with diarrhea.¹ Cytomegalovirus (CMV) infection/reactivation can occur in patients with corticosteroid refractory immune-mediated colitis.¹ In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.¹ When used as a single agent, immune-mediated colitis occurred in 1.1% (4/372) of patients receiving penpulimab kcqx, including Grade 2 (0.8%) and Grade 1 (0.3%) adverse reactions.¹ Systemic corticosteroids were required in 75% (3/4) of patients with colitis.¹ Colitis led to withholding of penpulimab-kcqx in 0.8% (3/372) of patients.¹

Immune-Mediated Hepatitis and Hepatotoxicity: Penpulimab-kcqx can cause immune-mediated hepatitis.¹ Immune-mediated hepatitis occurred in 0.7% (1/146) of patients receiving penpulimab kcqx in combination with either cisplatin or carboplatin and gemcitabine, which was a Grade 2 (0.7%) adverse reaction.¹ Systemic corticosteroids and withholding of penpulimab-kcqx were required in this patient.¹ When used as a single agent, immune-mediated hepatitis occurred in 3.8% (14/372) of patients receiving penpulimab-kcqx, including Grade 3 (0.8%), Grade 2 (1.3%) and Grade 1 (1.6%) adverse reactions.¹ Systemic corticosteroids were required in 14% (2/14) of patients with hepatitis.¹ Hepatitis led to permanent discontinuation of penpulimab-kcqx in 0.3% (1/372) and withholding of the drug in 2.2% (8/372) of patients.¹ Hepatitis resolved in 64% (9/14) of these patients.¹

Immune-Mediated Adrenal Insuffiency: Penpulimab-kcqx can cause primary or secondary adrenal insufficiency.¹ For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated.¹ Withhold penpulimab-kcqx depending on severity.¹

Immune-Mediated Hypophysitis: Penpulimab-kcqx can cause immune-mediated hypophysitis.¹ Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects.¹ Hypophysitis can cause hypopituitarism.¹ Initiate hormone replacement as indicated.¹ Withhold or permanently discontinue penpulimab-kcqx depending on severity.¹

Immune-Mediated Thyroid Disorders: Penpulimab-kcqx can cause immune-mediated thyroid disorders.¹ Thyroiditis can present with or without endocrinopathy.¹ Hypothyroidism can follow hyperthyroidism.¹ Initiate hormone replacement therapy for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated.¹ Withhold or permanently discontinue penpulimab-kcqx based on the severity.¹

Hyperthyroidism: Immune-mediated hyperthyroidism occurred in 2.1% (3/146) of patients receiving penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine, including Grade 2 (0.7%) and Grade 1 (1.4%) adverse reactions.¹ When used as a single agent, immune-mediated hyperthyroidism occurred in 7% (24/372) of patients receiving penpulimab-kcqx, including Grade 2 (1.1%) and Grade 1 (5%) adverse reactions.¹ Penpulimab-kcqx was withheld in 0.5% (2/372) of patients.¹ Hyperthyroidism resolved in 79% (19/24) of these patients.¹

Hypothyroidism: Immune-mediated hypothyroidism occurred in 16% (26/146) of patients receiving penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine, including Grade 2 (13%) and Grade 1 (4.8%) adverse reactions.¹ Penpulimab-kcqx was withheld in 0.7% (1/146) of patients.¹ Hypothyroidism resolved in 12% (3/26) of these patients.¹ When used as a single agent, immune-mediated hypothyroidism occurred in 19% (69/372) of patients receiving penpulimab-kcqx, including Grade 2 (7%) and Grade 1 (12%) adverse reactions.¹ Penpulimab-kcqx was withheld in 1.6% (6/372) of patients.¹ Hypothyroidism resolved in 48% (33/69) of these patients.¹

Thyroiditis:Thyroiditis occurred in 0.5% (2/372) of patients receiving penpulimab-kcqx, including Grade 2 (0.3%) and Grade 1 (0.3%) adverse reactions.¹ Thyroiditis led to withholding of penpulimab-kcqx in 0.3% (1/372) of patients.¹ Thyroiditis was resolved in 50% (1/2) of patients.¹

Type 1 Diabetes Mellitus, which can present with Diabetic Ketoacidosis: Monitor patients for hyperglycemia or other signs and symptoms of diabetes.¹ Initiate treatment with insulin as clinically indicated.¹ Withhold penpulimab-kcqx depending on severity.¹ Diabetes occurred in 2.7% (4/146) of patients receiving penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine, including Grade 4 (0.7%), Grade 3 (0.7%), Grade 2 (0.7%) and Grade 1 (0.7%) adverse reactions.¹ Diabetes led to permanent discontinuation of penpulimab-kcqx in 0.7% (1/146) and withholding of penpulimab-kcqx in 0.7% (1/146) of patients.¹ Diabetes was resolving in 75% (3/4) of these patients.¹ When used as a single agent, diabetes occurred in 0.8% (3/372) of patients receiving penpulimab-kcqx as a single agent, including Grade 1 (0.8%) adverse reactions.¹ Diabetes resolved in 67% (2/3) of these patients.¹

Immune-Mediated Nephritis with Renal Dysfunction: Penpulimab-kcqx can cause immune-mediated nephritis and renal dysfunction.¹ When used as a single agent, immune-mediated nephritis occurred in 0.5% (2/372) of patients receiving penpulimab-kcqx, including Grade 3 (0.3%) and Grade 2 (0.3%) adverse reactions.¹ Immune-mediated nephritis led to permanent discontinuation of penpulimab-kcqx in 0.5% (2/372) of patients.¹ Systemic corticosteroids were required in 50% (1/2) of patients.¹ Nephritis resolved in 50% (1/2) of these patients.¹

Immune-Mediated Dermatologic Adverse Reactions: Penpulimab-kcqx can cause immune-mediated rash or dermatitis.¹ Exfoliative dermatitis, including Stevens Johnson Syndrome (SJS), Drug Rash with Eosinophilia and Systemic Symptoms (DRESS), and Toxic Epidermal Necrolysis (TEN) has occurred with PD-1/L-1 blocking antibodies.¹ Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes.¹ Withhold or permanently discontinue penpulimab-kcqx depending on severity.¹ Immune-mediated rash or dermatitis occurred in 10% (14/146) of patients receiving penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine, including Grade 3 (0.7%), Grade 2 (4.8%) and Grade 1 (4.1%) adverse reactions.¹ Systemic corticosteroids were required in 36% (5/14) of patients with immune-mediated rash or dermatitis.¹ Immune-mediated rash or dermatitis led to withholding of penpulimab-kcqx in 1.4% (2/146) of patients.¹ Immune-mediated rash or dermatitis resolved in 78.6% (11/14) of these patients.¹ When used as a single agent, immune-mediated rash or dermatitis occurred in 12% (43/372) of patients receiving penpulimab-kcqx, including Grade 3 (1.3%), Grade 2 (3.5%) and Grade 1 (7%) adverse reactions.¹ Systemic corticosteroids were required in 14% (6/43) of patients with immune-mediated rash or dermatitis.¹ Immune-mediated rash or dermatitis led to permanent discontinuation of penpulimab-kcqx in 0.3% (1/372) and withholding of penpulimab-kcqx in 1.6% (6/372) of patients.¹ Immune-mediated rash or dermatitis resolved in 58% (25/43) of these patients.¹

Other Immune-Mediated Adverse Reactions: The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine or single-agent penpulimab-kcqx or were reported with the use of other PD-1/PD-L1 blocking antibodies.¹ Severe or fatal cases have been reported for some of these adverse reactions.¹

Cardiac/vascular: Myocarditis, pericarditis, vasculitis. ¹

Nervous system: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy, nerve injury. ¹

Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur.¹ Some cases can be associated with retinal detachment.¹ Various grades of visual impairment including blindness can occur.¹ If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss. ¹

Gastrointestinal: Pancreatitis to include increases in serum amylase and lipase levels, gastritis, duodenitis. ¹

Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatic. ¹

Endocrine: Hypoparathyroidism. ¹

Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (including corneal graft) rejection. ¹

Infusion-related Reactions

Penpulimab-kcqx can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis.¹ Discontinue penpulimab-kcqx in patients with severe or life-threatening infusion-related reactions.¹ Interrupt or slow the rate of infusion in patients with mild or moderate infusion-related reactions.¹

Infusion-related reactions occurred in 3.4% of 146 patients receiving penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine, including Grade 2 (1.4%) and Grade 1 (2.1%) infusion related reactions.¹ Infusion-related reactions occurred in 10% of 372 patients receiving penpulimab-kcqx as single agent, including Grade 4 (0.3%), Grade 3 (0.3%), Grade 2 (6%) and Grade 1 (3.8%) infusion related reactions.¹ Penpulimab-kcqx was withheld in 0.8% (3/372) and permanently discontinued in 0.3% (1/372) of patients.¹

Complications of Allogeneic HSCT

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody.¹ Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause).¹ These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT.¹

Follow patients closely for evidence of transplant-related complications and intervene promptly.¹ Consider the benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody prior to or after an allogeneic HSCT.¹

Embryo-fetal Toxicity

Based on its mechanism of action, penpulimab-kcqx can cause fetal harm when administered to a pregnant woman.¹ Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death.¹ Advise pregnant women of the potential risk to a fetus.¹ Advise females of reproductive potential to use effective contraception during treatment with penpulimab-kcqx and for 4 months after the last dose.¹

Specific Populations

Pregnancy

Based on its mechanism of action, penpulimab-kcqx can cause fetal harm when administered to a pregnant woman.¹ There are no available data on the use of penpulimab-kcqx in pregnant women.¹ Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death.¹ Human immunoglobulin G (IgG) is known to cross the placental barrier; therefore, penpulimab-kcqx has the potential to be transmitted from the mother to the developing fetus.¹ Advise women of the potential risk to a fetus.¹

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.¹

Lactation

There is no information regarding the presence of penpulimab-kcqx in human milk or its effects on the breastfed child, or on milk production.¹ Maternal IgG is known to be present in human milk. The effects of local GI exposure and limited systemic exposure in the breastfed child to penpulimab-kcqx are unknown.¹ Because of the potential for serious adverse reactions in a breastfed child, advise lactating women not to breastfeed during treatment and for 4 months after the last dose of penpulimab-kcqx.¹

Females and Males of Reproductive Potential

Penpulimab-kcqx can cause fetal harm when administered to a pregnant woman.¹ Verify pregnancy status in females of reproductive potential prior to initiating penpulimab-kcqx.¹

Advise females of reproductive potential to use effective contraception during treatment with penpulimab-kcqx and for 4 months after the last dose.¹

Pediatric Use

The safety and effectiveness of penpulimab-kcqx have not been established in pediatric patients. ¹

Geriatric Use

Of the 146 patients with NPC who received penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine, 15 (10%) were 65 years or older and 1 (0.7%) was 75 years or older.¹ Clinical studies did not include a sufficient number of patients 65 years of age or older to determine differences in safety or effectiveness compared to younger patients. ¹

Of the 372 patients with NPC who received penpulimab-kcqx as a single agent, 69 (19%) were 65 years or older and 7% were 75 years and older.¹ No overall differences in safety or effectiveness were observed between patients <65 years and those 65 years.¹

Common Adverse Effects

Penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine: The most common adverse reactions (≥20%) were nausea, vomiting, hypothyroidism, constipation, decreased appetite, decreased weight, cough, COVID-19 infection, fatigue, rash, and pyrexia.¹

Penpulimab-kcqx as a single agent: The most common adverse reactions (≥20%) were anemia and hypothyroidism.¹

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

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.¹ 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.¹ Penpulimab-kcqx injection is a humanized IgG1 monoclonal antibody that binds to PD-1 and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the antitumor immune response.¹ In murine tumor models, blocking PD-1 activity resulted in decreased tumor growth.¹

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling (Medication Guide).¹

• Inform patients of the risk of immune-mediated adverse reactions that may be severe or fatal, may occur after discontinuation of treatment, and may require corticosteroid treatment and interruption or discontinuation of penpulimab-kcqx.¹

• Risk of pneumonitis.¹ Advise patients to contact their healthcare provider immediately for new or worsening cough, chest pain, or shortness of breath.¹

• Risk of colitis.¹ Advise patients to contact their healthcare provider immediately for diarrhea or severe abdominal pain.¹

• Risk of hepatitis.¹ Advise patients to contact their healthcare provider immediately for jaundice, severe nausea or vomiting, or easy bruising or bleeding.¹

• Risk of endocrinopathies.¹ Advise patients to contact their healthcare provider immediately for signs or symptoms of adrenal insufficiency, hypophysitis, hypothyroidism, hyperthyroidism, or Type 1 diabetes mellitus.¹

• Risk of nephritis.¹ Advise patients to contact their healthcare provider immediately for signs or symptoms of nephritis including decreased urine output, blood in urine, swelling in ankles, loss of appetite, and any other symptoms of renal dysfunction.¹

• Risk of severe skin reactions.¹ Advise patients to contact their healthcare provider immediately for any signs or symptoms of severe skin reactions, Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis, including rash or any other severe skin discomfort.¹

• Advise patients that immune-mediated adverse reactions may involve any organ system, and to contact their healthcare provider immediately for any new or worsening signs or symptoms.¹

• Advise patients of the risk of solid organ transplant rejection and other transplant (including corneal graft) rejection.¹ Advise patients to contact their healthcare provider immediately for signs or symptoms of organ transplant rejection and other transplant (including corneal graft) rejection.¹

• Advise patients to contact their healthcare provider immediately for signs or symptoms of infusion-related reactions.¹

• Advise patients of the risk of post-allogeneic hematopoietic stem cell transplantation complications.¹

• Advise females of reproductive potential that penpulimab-kcqx can cause harm to a fetus and to inform their healthcare provider of a known or suspected pregnancy.¹

• Advise females of reproductive potential to use effective contraception during treatment and for 4 months after the last dose of penpulimab-kcqx.¹

• Advise female patients not to breastfeed while taking penpulimab-kcqx and for 4 months after the last dose.¹

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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