Penpulimab: Drug information

For additional information see "Penpulimab: Patient drug information"

For abbreviations, symbols, and age group definitions show table

Pharmacologic Category

Antineoplastic Agent, Anti-PD-1 Monoclonal Antibody;
Antineoplastic Agent, Immune Checkpoint Inhibitor;
Antineoplastic Agent, Monoclonal Antibody

Dosing: Adult

Nasopharyngeal carcinoma, nonkeratinizing, recurrent or metastatic

Nasopharyngeal carcinoma, nonkeratinizing, recurrent or metastatic:

First-line treatment: IV: 200 mg once every 3 weeks (in combination with gemcitabine and either cisplatin or carboplatin) for 6 cycles, followed by penpulimab 200 mg once every 3 weeks (as a single agent); continue until disease progression or unacceptable toxicity for a maximum of 24 months (Ref).

Previously treated: IV: 200 mg once every 2 weeks (as a single agent); continue until disease progression or unacceptable toxicity for a maximum of 24 months (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Kidney impairment prior to treatment initiation:

CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling; however, no clinically significant difference in penpulimab pharmacokinetics was observed in patients with mild or moderate kidney function impairment.

CrCl <30 mL/minute : There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Kidney toxicity during treatment:

Immune-mediated nephritis with kidney dysfunction: General information: If penpulimab treatment interruption or discontinuation is required, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone [or equivalent]) or other appropriate therapy for immune-mediated adverse reactions until improvement to grade 1 or lower, then follow with a corticosteroid taper over at least 1 month. Consider administration of other systemic immunosuppressants if immune-mediated adverse reaction is not controlled with corticosteroid therapy (Ref).

**Penpulimab Recommended Dosage Modifications for Ac** **ute Immune-Mediated Nephritis During Treatment**
Adverse reaction	Severity^a	Penpulimab dosage modification^b
^a SCr elevation grade levels (NCI CTCAE version 5): Grade 0 or 1: SCr ≤1.5 times baseline; SCr ≤1.5 times ULN Grade 2: SCr >1.5 to 3 times baseline; SCr >1.5 to ≤3 times ULN Grade 3: SCr >3 times baseline; SCr >3 to ≤6 times ULN Grade 4: SCr >6 times ULN.
^bManufacturer’s labeling
^cRefer to prednisone monograph for tapering recommendations when used for immune-mediated adverse reactions associated with checkpoint inhibitor therapy.
Immune-mediated nephritis with kidney dysfunction	Grade 2 or 3^aSCr elevation	Withhold penpulimab; resume penpulimab after complete or partial (to grade 0 or 1^a) resolution after corticosteroid taper.^c Permanently discontinue penpulimab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.^b
Immune-mediated nephritis with kidney dysfunction	Grade 4^a SCr elevation	Permanently discontinue penpulimab.^b

Dosing: Liver Impairment: Adult

Hepatic impairment prior to treatment initiation:

Mild (total bilirubin ≤ ULN and AST > ULN or total bilirubin >1 to 1.5 × ULN and any AST) to moderate (total bilirubin >1.5 to 3 × ULN and any AST) impairment: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant difference in penpulimab pharmacokinetics was observed in patients with mild to moderate hepatic impairment.

Severe impairment (total bilirubin >3 × ULN and any AST): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Acute hepatotoxicity during treatment:

General information: Abnormal liver enzymes should be evaluated to differentiate immune-mediated adverse reactions from other etiologies (eg, new or progressive liver metastases, viral hepatitis, thromboembolism) (Ref). If penpulimab treatment interruption or discontinuation is required, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone [or equivalent]) or other appropriate therapy for immune-mediated adverse reactions until improvement to ≤ grade 1, then follow with a corticosteroid taper over at least 1 month. Consider administration of other systemic immunosuppressants if immune-mediated adverse reaction is not controlled with corticosteroid therapy (Ref).

**Penpulimab Recommended Dosage Modifications for Ac** **ute Immune-Mediated Hepatoxicity During Treatment**
Adverse reaction	Severity	Penpulimab dosage modification
^aManufacturer’s labeling.
^bRefer to prednisone monograph for tapering recommendations when used for immune-mediated adverse reactions associated with checkpoint inhibitor therapy.
^c ASCO (Schneider 2021).
^dLi 2022.
Immune-mediated hepatitis without tumor involvement of the liver	AST or ALT >3 up to 8 times ULN or total bilirubin >1.5 up to 3 times ULN	Withhold penpulimab; resume penpulimab after complete or partial (to grade 0 or 1 [AST or ALT ≤3 times ULN] or total bilirubin ≤1.5 times ULN]) resolution after corticosteroid taper.^a,b Permanently discontinue penpulimab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.^a
	Single-agent therapy: AST or ALT >3 up to 5 times ULN and/or total bilirubin >1.5 up to 3 times ULN	Guideline recommendations : Withhold penpulimab. Delayed initiation of lower dose corticosteroids (0.5 to 1 mg/kg/day prednisone [or equivalent]) may be considered if no improvement following 3 to 5 days of treatment interruption.^c
	AST or ALT >8 times ULN or total bilirubin >3 times ULN	Permanently discontinue penpulimab.^a
	Single-agent therapy: AST or ALT >5 times ULN and/or total bilirubin >3 times ULN or Symptomatic liver dysfunction, fibrosis (biopsy confirmed), compensated/ decompensated cirrhosis, or reactivation of chronic hepatitis	Guideline recommendations : Withhold immune checkpoint inhibitor; immediately initiate corticosteroids (methylprednisolone 1 to 2 mg/kg or equivalent). Consider permanent discontinuation if asymptomatic, permanently discontinue penpulimab if symptomatic.^c Based on data from a retrospective cohort study in patients with grade 3 or 4 immune-mediated hepatitis, initial treatment with methylprednisolone 1 mg/kg/day demonstrated similar time to ALT normalization (compared with higher methylprednisolone doses), while reducing the potential for corticosteroid-related complications.^d
Immune-mediated hepatitis with tumor involvement of the liver Note: If AST and ALT are ≤ ULN at baseline, follow recommendations for hepatitis without tumor involvement of the liver.	Baseline AST or ALT >1 up to 3 times ULN and increases to >5 up to 10 times ULN or Baseline AST or ALT >3 up to 5 times ULN and increases to >8 up to 10 times ULN	Withhold penpulimab; resume penpulimab after complete or partial (to grade 0 or 1 [AST or ALT ≤3 times ULN]) resolution after corticosteroid taper.^a,b Permanently discontinue penpulimab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.^a
	AST or ALT increases to >10 times ULN or total bilirubin increases to >3 times ULN	Permanently discontinue penpulimab.^a

Dosing: Obesity: Adult

American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m²: The dosing in the approved prescribing information should be followed in all patients, regardless of obesity status. If a patient with a BMI ≥30 kg/m²experiences high-grade toxicity from systemic anticancer therapy, the same dosage modification recommendations should be followed for all patients, regardless of obesity status (Ref).

Dosing: Adjustment for Toxicity: Adult

Note: No dosage reductions of penpulimab are recommended. Other concomitant anticancer therapies may also require treatment interruption, dosage reduction, and/or discontinuation.

Immune-mediated adverse reactions (general information): Withhold penpulimab for severe (grade 3) immune-mediated adverse reactions. Permanently discontinue penpulimab for life-threatening (grade 4) immune-mediated adverse reactions, recurrent severe (grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or inability to reduce corticosteroid dose to prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating corticosteroids. If penpulimab treatment interruption or discontinuation is required, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone [or equivalent]) until improvement to ≤ grade 1; upon improvement to ≤ grade 1, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants if immune-mediated adverse reaction is not controlled with corticosteroid therapy. Systemic corticosteroids may not be necessary for certain adverse reactions. Hormone replacement therapy may be required for endocrinopathies (if clinically indicated). See table for additional dosage modification guidance.

Additional guideline-based management recommendations: Consider withholding checkpoint inhibitor therapy for select grade 1 toxicities (eg, aseptic meningitis, encephalitis, immune-mediated neuropathy, aplastic anemia, acquired thrombotic thrombocytopenic purpura [TTP], acquired hemophilia A, troponin elevation). For most grade 2 toxicities, consider withholding checkpoint inhibitor therapy and resume when symptoms and/or lab values resolve to ≤ grade 1; systemic corticosteroids (initial dose of 0.5 to 1 mg/kg/day prednisone [or equivalent]) may be administered if indicated for grade 2 toxicities (Ref). Refer to guideline for further information regarding management of immune-mediated adverse reactions associated with checkpoint inhibitor therapy.

**Penpulimab Recommended Dosage Modifications for Adverse Reactions^a**
Adverse reaction	Severity	Penpulimab dosage modification
^aSJS = Stevens-Johnson syndrome (SJS); TEN = toxic epidermal necrolysis; DRESS = drug rash with eosinophilia and systemic symptoms.
^bRefer to prednisone monograph for tapering recommendations when used for immune-mediated adverse reactions associated with checkpoint inhibitor therapy.
Immune-mediated adverse reactions
Cardiovascular toxicity: Myocarditis	Grade 2, 3, or 4	Permanently discontinue penpulimab.
Dermatologic toxicity	Mild or moderate nonexfoliative rash	May be managed with topical emollients and/or topical corticosteroids.
	Exfoliative dermatologic conditions: Suspected SJS, TEN, or DRESS	Withhold penpulimab; resume penpulimab after complete or partial (to grade 0 or 1) resolution after corticosteroid taper.^b Permanently discontinue penpulimab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.
	Confirmed SJS, TEN, or DRESS	Permanently discontinue penpulimab.
Endocrinopathies	Grade 3 or 4	Withhold penpulimab until clinically stable or permanently discontinue depending on severity.
	Adrenal insufficiency, ≥ grade 2	Withhold penpulimab (depending on the severity). Initiate symptomatic management (including hormone replacement as clinically indicated).
	Diabetes, type 1	Withhold penpulimab (depending on the severity). Initiate insulin as clinically indicated. Long-term insulin therapy may be required.
	Hypophysitis	Withhold or permanently discontinue penpulimab (depending on the severity). Initiate hormone replacement therapy as clinically indicated.
	Hyperthyroidism	Withhold or permanently discontinue penpulimab (depending on the severity). Initiate medical management as clinically indicated.
	Hypothyroidism	Withhold or permanently discontinue penpulimab (depending on the severity). Initiate thyroid hormone replacement therapy as clinically indicated.
GI toxicity: Colitis	Grade 2 or 3	Withhold penpulimab; resume penpulimab after complete or partial (to grade 0 or 1) resolution after corticosteroid taper.^b Permanently discontinue penpulimab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.
GI toxicity: Colitis	Grade 4	Permanently discontinue penpulimab.
Neurologic toxicities	Grade 2	Withhold penpulimab; resume penpulimab after complete or partial (to grade 0 or 1) resolution after corticosteroid taper.^b Permanently discontinue penpulimab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.
Neurologic toxicities	Grade 3 or 4	Permanently discontinue penpulimab.
Ocular disorders: Vogt-Koyanagi-Harada–like syndrome		May require systemic corticosteroids to reduce the risk of permanent vision loss.
Pulmonary toxicity: Pneumonitis	Grade 2	Withhold penpulimab; resume penpulimab after complete or partial (to grade 0 or 1) resolution after corticosteroid taper.^b Permanently discontinue penpulimab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.
Pulmonary toxicity: Pneumonitis	Grade 3 or 4	Permanently discontinue penpulimab.
Other adverse reactions
Infusion reactions	Grade 1 or 2	Interrupt or slow the rate of penpulimab infusion.
Infusion reactions	Grade 3 or 4	Stop infusion and permanently discontinue penpulimab.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults. Reactions listed may be reported for other agents in the same pharmacological class (PD-1/PD-L1-blocking antibodies) and may not be specifically reported for penpulimab.

>10%:

Dermatologic: Dermatitis (≤12%), skin rash (≤12%; including acneiform eruption, eczema, pemphigoid)

Endocrine & metabolic: Decreased serum albumin (45%), decreased serum magnesium (28%), decreased serum phosphate (47%), decreased serum sodium (46%), hypothyroidism (19% to 39%), increased serum glucose (34%), increased serum triglycerides (38%), weight loss (19%)

Hematologic & oncologic: Anemia (25%), lymphocytopenia (43%; grades 3/4: 11% to 16%), prolonged partial thromboplastin time (22%)

Hepatic: Increased gamma-glutamyl transferase (34%), increased serum alanine aminotransferase (20%), increased serum alkaline phosphatase (35%), increased serum aspartate aminotransferase (33%)

Neuromuscular & skeletal: Musculoskeletal pain (25%; including arthralgia, back pain, limb pain, musculoskeletal chest pain, neck pain, noncardiac chest pain, ostealgia)

Renal: Increased serum creatinine (81%)

Respiratory: Cough (11%), upper respiratory tract infection (13%)

Miscellaneous: Fever (15%)

1% to 10%:

Endocrine & metabolic: Hypermagnesemia (grades 3/4: 3%), hyperthyroidism (7%)

Gastrointestinal: Colitis (1%)

Hematologic & oncologic: Decreased platelet count (grades 3/4: 3%)

Hepatic: Hepatitis (4%), increased serum bilirubin (grades 3/4: 3%)

Hypersensitivity: Infusion-related reaction (10%)

Respiratory: Pneumonitis (1%)

<1%:

Cardiovascular: Myocarditis, pericarditis, vasculitis

Endocrine & metabolic: Diabetes mellitus, hypoparathyroidism, thyroiditis

Gastrointestinal: Duodenitis, gastritis, increased serum amylase, increased serum lipase, pancreatitis

Hematologic & oncologic: Aplastic anemia, hemolytic anemia, hemophagocytic lymphohistiocytosis, immune thrombocytopenia, lymphadenitis (histiocytic necrotizing lymphadenitis [Kikuchi lymphadenitis])

Immunologic: Organ transplant rejection (corneal graft, solid), sarcoidosis

Infection: Systemic inflammatory response syndrome

Nervous system: Demyelinating disease, encephalitis, Guillain-Barré syndrome, meningitis, myasthenia (myasthenic syndrome), myasthenia gravis (including exacerbation of myasthenia gravis), neuropathy (autoimmune), nerve injury, paresis (nerve)

Neuromuscular & skeletal: Myelitis, myositis, polymyositis, rhabdomyolysis

Ophthalmic: Iritis, uveitis

Renal: Nephritis

Frequency not defined:

Hematologic & oncologic: Decreased white blood cell count

Hepatic: Herpes zoster infection

Nervous system: Spinal cord compression

Respiratory: Pleural effusion, pneumonia, respiratory failure

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Warnings/Precautions

Concerns related to adverse effects:

• Adverse reactions (immune-mediated): PD-1/PD-L1 blockers (including penpulimab) remove immune response inhibition, thus potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Severe and fatal immune-mediated adverse reactions may occur in any organ system or tissue. Reactions generally occur during treatment (may occur at any time after penpulimab initiation); reactions may also occur after penpulimab discontinuation. Early identification and management of immune-mediated adverse reactions are necessary to ensure safe use of penpulimab. If suspected immune-mediated reactions occur, initiate appropriate workup to exclude alternative causes (including infection).

• Dermatologic toxicity: Penpulimab may cause immune-mediated rash or dermatitis; grade 1 to 3 events have been reported. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis have occurred with other anti-PD-L1/PD-1 monoclonal antibodies. Systemic corticosteroids were required in approximately one-fifth of patients with penpulimab-associated immune-mediated dermatologic rash or dermatitis. Dermatologic adverse reactions led to treatment interruption or permanent discontinuation in a small number of patients. Immune-mediated dermatologic adverse reactions resolved in almost two-thirds of patients.

• Endocrinopathies: Penpulimab is associated with immune-mediated endocrinopathies.

Adrenal insufficiency: Penpulimab may cause primary or secondary adrenal insufficiency.
Diabetes mellitus: Type 1 diabetes mellitus has been reported with PD-1 and PD-L1 blocking antibodies (including penpulimab). Grade 1 to 4 diabetes mellitus events occurred. Treatment interruption and discontinuation were required rarely. A majority of patients had resolving or resolved diabetes mellitus following treatment interruption or permanent discontinuation.
Hypophysitis: Penpulimab may cause immune-mediated hypophysitis. Hypophysitis may present with acute mass effect–associated symptoms such as headache, photophobia, or visual field defects. Hypophysitis may cause hypopituitarism.
Thyroid disorders: Penpulimab may cause immune-mediated thyroid disorders. Hyperthyroidism occurred in a small percentage of patients, including grade 1 or 2 events. Treatment interruption was rarely required. Hyperthyroidism resolved in a majority of patients. Hypothyroidism has also occurred, including grades 1 and 2 events. Hypothyroidism may follow hyperthyroidism. Treatment interruption was required in a small number of patients for hypothyroidism. Hypothyroidism resolved in approximately one-third of patients. Thyroiditis occurred rarely, including grade 1 and 2 events; treatment interruption was necessary for thyroiditis in some cases, and thyroiditis resolved in one-half of patients. Thyroiditis can present with or without endocrinopathy.

• GI adverse reactions: Penpulimab may cause immune-mediated colitis, which may present with diarrhea. Immune-mediated colitis occurred in a small number of patients, including grade 1 and 2 events. Systemic corticosteroids were required in three-fourths of patients with colitis; some patients required treatment interruption. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis who received anti-PD-L1/PD-1 monoclonal antibodies. Pancreatitis (including increased serum amylase and lipase levels), gastritis, and duodenitis have also been reported.

• Hepatitis: Penpulimab may cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in a small number of patients, including grades 1 to 3 events. Systemic corticosteroids, treatment interruption, or permanent discontinuation were required in some patients with hepatitis. Hepatitis resolved in approximately two-thirds of patients.

• Infusion-related reactions: Penpulimab may cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis. Infusion reactions occurred in a small percentage of patients, and were usually grades 1 or 2, although rare grade 3 and 4 reactions were observed.

• Kidney toxicity: Penpulimab may cause immune-mediated nephritis with kidney dysfunction. Grades 2 and 3 events have occurred rarely. Nephritis led to permanent discontinuation in some cases. Systemic corticosteroids were required in one-half of patients with nephritis, with resolution in one-half of those treated with corticosteroids.

• Ocular disorders: Ocular events, including uveitis, iritis, and other ocular inflammatory toxicities have been reported either with penpulimab or with other anti-PD-L1/PD-1 monoclonal antibodies; some cases may be associated with retinal detachment. Various grades of visual impairment (including blindness) may occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada–like syndrome.

• Pneumonitis: Penpulimab may cause immune-mediated pneumonitis. In patients who received other anti-PD-L1/PD-1 monoclonal antibodies, the incidence of pneumonitis was higher in patients who received prior thoracic radiation. Immune-mediated pneumonitis occurred in a small number of penpulimab-treated patients; including grades 1 to 3 events. Pneumonitis led to permanent discontinuation or treatment interruption rarely. Systemic corticosteroids were required in a majority of patients with pneumonitis. Pneumonitis resolved in one-fifth of cases.

• Other immune-mediated toxicities: Other clinically significant immune-mediated adverse reactions have been reported rarely with penpulimab or with other anti-PD-L1/PD-1 monoclonal antibodies (some have been severe or fatal). Events have included meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barre syndrome, nerve paresis, autoimmune neuropathy, nerve injury, myocarditis, pericarditis, vasculitis, myositis/polymyositis, rhabdomyolysis (and associated sequelae including kidney failure), arthritis, polymyalgia rheumatica, hypoparathyroidism, hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia (formerly known as immune thrombocytopenic purpura), solid organ transplant rejection, and other transplant (including corneal graft) rejection.

Disease-related concerns:

• Hematopoietic cell transplant: Fatal and other serious complications may occur in patients who receive allogeneic hematopoietic cell transplant (HCT) before or after treatment with an anti-PD-L1/PD-1 monoclonal antibody. Transplant-related complications included hyperacute graft-versus-host disease (GVHD), acute or chronic GVHD, hepatic veno-occlusive disease (also known as sinusoidal obstruction syndrome) after reduced-intensity conditioning, and steroid-requiring febrile syndrome (with no identified infectious etiology). These complications may occur despite intervening therapy between PD-L1/PD-1 blockade and allogeneic HCT. Manage early signs/symptoms of transplant-related complications promptly. Assess the risks/benefits of treatment with an anti-PD-L1/PD-1 monoclonal antibody prior to or after an allogeneic HCT.

• Myasthenia gravis: Checkpoint inhibitors may worsen or precipitate new myasthenia gravis (MG), especially within the first 16 weeks of treatment; use with caution. Patients with well-controlled MG may be considered for checkpoint inhibitor therapy if MG treatment is maintained (or reinitiated in patients whose MG is in remission), combination therapy (eg, anti–CTLA-4 with anti–PD-a/PD-L1 monoclonal antibodies) is avoided, and respiratory and bulbar function are closely followed. In patients who develop overt MG during checkpoint inhibitor therapy, early aggressive treatment with plasma exchange or IVIG in combination with high-dose corticosteroids may be required (Ref).

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Ref). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Ref). See manufacturer's labeling.

Product Availability

Penpulimab: FDA approved April 2025; anticipated availability is currently unknown.

Administration: Adult

IV: Infuse over 60 minutes through an IV line with a 0.2- to 0.22-micron sterile, nonpyrogenic, low-protein binding inline or add-on filter. Do not infuse other medications through the same infusion line.

Administration sequence (for combination therapy):

Nasopharyngeal cancer, recurrent or metastatic (first-line treatment): When administered in combination with gemcitabine and platinum chemotherapy, administer penpulimab first, followed by gemcitabine, followed by the platinum agent (Ref).

Use: Labeled Indications

Nasopharyngeal carcinoma, nonkeratinizing, recurrent or metastatic:

First-line treatment (in combination with gemcitabine and either cisplatin or carboplatin) of recurrent or metastatic nonkeratinizing nasopharyngeal carcinoma (NPC) in adults.

Treatment (as a single agent) of metastatic nonkeratinizing NPC with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy in adults.

Medication Safety Issues

Sound-alike/look-alike issues:

Penpulimab may be confused with atezolizumab, avelumab, cemiplimab, cosibelimab, dostarlimab, durvalumab, ipilimumab, nivolumab, pembrolizumab, retifanlimab, tislelizumab, toripalimab, tremelimumab.

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) that have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Acetaminophen: May decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor

Antibiotics: May decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor

Corticosteroids (Systemic): May decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Management: Carefully consider the need for corticosteroids, at doses of a prednisone-equivalent of 10 mg or more per day, during the initiation of immune checkpoint inhibitor therapy. Use of corticosteroids to treat immune related adverse events is still recommended Risk D: Consider Therapy Modification

Efgartigimod Alfa: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor

Inhibitors of the Proton Pump (PPIs and PCABs): May decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor

Ketoconazole (Systemic): Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies) may increase hepatotoxic effects of Ketoconazole (Systemic). Risk C: Monitor

Nipocalimab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor

Opioid Agonists: Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies) may decrease therapeutic effects of Opioid Agonists. Opioid Agonists may decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor

Rozanolixizumab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor

Vitamin K Antagonists: Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies) may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor

Reproductive Considerations

Verify pregnancy status prior to therapy. Patients who could become pregnant should use effective contraception during therapy and for 4 months after the last penpulimab dose.

Endocrine-related adverse events during treatment with PD-1 immune checkpoint inhibitors may have direct or indirect effects on fertility that may be reversible; however, human data are limited. Consider evaluating fertility status prior to treatment, the patients desire for future pregnancies, and (if desired), options for fertility preservation (Ref).

Pregnancy Considerations

Penpulimab is a recombinant human immunoglobulin (IgG₁) monoclonal antibody. Human IgG crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Ref).

Animal reproduction studies have not been conducted with penpulimab. Based on the mechanism of action, in utero exposure to penpulimab may disrupt maternal tolerance to the fetus, increasing the risk of abortion or stillbirth. Based on animal data, maternal use of a PD-1 inhibitor may also result in immune-mediated disorders in the newborn.

The European Society for Medical Oncology (ESMO) has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy. The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team) approach (Ref).

A long-term observational research study is collecting information about the diagnosis and treatment of cancer during pregnancy. For additional information about the pregnancy and cancer registry or to become a participant, contact Cooper Health (877-635-4499).

Breastfeeding Considerations

It is not known if penpulimab is present in breast milk.

Penpulimab is a recombinant human immunoglobulin (IgG₁) monoclonal antibody. Human IgG is present in breast milk; concentrations are dependent upon IgG subclass and postpartum age (Ref).

Due to the potential for adverse events in the breastfed infant, the manufacturer does not recommended breastfeeding during therapy or for 4 months after the last penpulimab dose.

Monitoring Parameters

Monitor hepatic function (AST, ALT, and total bilirubin; at baseline and periodically during treatment); kidney function (SCr; at baseline and periodically during treatment); thyroid function (at baseline, periodically during treatment, and as clinically indicated); monitor blood glucose (for hyperglycemia). Verify pregnancy status (prior to therapy in patients who could become pregnant).

Monitor closely for signs/symptoms of immune-mediated adverse reactions, including adrenal insufficiency, diarrhea/colitis (consider initiating or repeating infectious workup in patients with corticosteroid-refractory immune-mediated colitis to exclude alternative causes), dermatologic toxicity, diabetes mellitus, hypophysitis/hypopituitarism, neurologic toxicity, ocular disorders, thyroid disorders, pneumonitis, and other immune-mediated adverse reactions. Monitor for signs/symptoms of infusion-related reactions. If received/receiving a hematopoietic cell transplant, monitor closely for early signs/symptoms of transplant-related complications.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (Ref) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Additional suggested monitoring (Ref): Prior to therapy: CBC with differential; creatine kinase; comprehensive clinical assessment including performance status, weight, body mass index, heart rate, BP, and oxygen saturation; consider chest x-ray, electrocardiogram, and CT scan; assess history of autoimmune conditions, organ-specific disease, endocrinopathies, neuropathy, and infectious disease; assess bowel habits, respiratory symptoms, skin (for rash), arthralgias, and neurologic symptoms. During therapy: Assess BP, weight, heart rate, and oxygen saturation; assess for infections; screen for hyperglycemia/diabetes (polyuria, polydipsia, weight loss); eye exam (including intraocular pressure after 6 weeks); CBC with differential; creatine kinase; monitor bone mineral density (with long-term therapy).

Cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (Ref). Obtain baseline ECG, natriuretic peptides, and troponins in all patients; obtain a baseline echocardiogram in high-risk patients; consider serial ECGs and cardiac troponins prior to doses 2, 3, and 4, and if normal, reduce to every 3 doses until completion of therapy; cardiovascular risk assessment every 6 to 12 months in high-risk patients who require long-term (>12 months therapy, consider cardiovascular risk assessment every 6 to 12 months in all patients requiring long-term therapy) (Ref). Refer to a cardiologist when clinically indicated.

Mechanism of Action

Penpulimab is a recombinant humanized IgG₁ monoclonal antibody that inhibits programmed death-1 (PD-1) activity by binding to the PD-1 receptor found on T cells to block the ligands PD-L1 and PD-L2 from binding. This releases PD-1 pathway-mediated inhibition of immune response, including antitumor response. PD-1 ligand upregulation occurs in some tumors, and signaling through this pathway can contribute to the inhibition of active T-cell immune surveillance of tumors. Blocking PD-1 activity has resulted in decreased tumor growth.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: V_d: 10 L.

Metabolism: Penpulimab is expected to be metabolized into small peptides via catabolic pathways.

Half-life elimination: 32 days.

Excretion: Clearance: 0.2 L/day.

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Penpulimab [prescribing information]. Zhongshan, Guangdong, China: Akeso Biopharma Co Ltd; April 2025.
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Refer to manufacturer's labeling.
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