Penpulimab-kcqx, a recombinant humanized anti-programmed-death receptor-1 (anti-PD-1) monoclonal antibody, is an antineoplastic agent.1
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 has been designated an orphan drug by FDA for the treatment of NPC.2
First-line Treatment of Recurrent or Metastatic Non-Keratinizing NPC
Safety and efficacy of penpulimab-kcqx for the first-line treatment of recurrent or metastatic non-keratinizing NPC in combination with either cisplatin or carboplatin and gemcitabine in adults were evaluated in a randomized, multicenter, double-blind, placebo-controlled, phase 3 trial (AK105-304).1, 3, 4 A total of 291 patients, 18-75 years of age with recurrent or metastatic NPC with no prior systemic chemotherapy in the recurrent or metastatic setting, were randomized in a 1:1 ratio to receive penpulimab-kcqx or placebo in combination with gemcitabine and cisplatin or carboplatin once every 3 weeks for up to 6 cycles, followed by penpulimab-kcqx or placebo maintenance once every 3 weeks for a maximum of 24 months.1, 3 During the chemotherapy phase, patients received either IV penpulimab-kcqx 200 mg or placebo, IV gemcitabine 1000 mg/m2 on days 1 and 8, and either IV cisplatin 80 mg/m2 on day 1 or IV carboplatin dosed to an AUC of 5 on day 1 of each 3-week cycle for up to 6 cycles.1, 3 During the maintenance phase, patients continued to receive penpulimab-kcqx or placebo every 3 weeks until progressive disease, intolerable toxicity, withdrawal of consent, or a maximum of 24 months.1, 3 The primary endpoint was progression-free survival (PFS) as evaluated by a blinded independent central review (BICR) committee according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1).1, 3 A key secondary endpoint was overall survival (OS).1, 3 Other secondary endpoints included overall response rate and duration of response.1, 3
Among the patients enrolled in AK105-304, the median age was 51 years (range 23-75 years); 10% were 65 years of age or older, 82% were male, 98% were Asian, 36% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0, and 80% had metastatic disease at study entry.1, 4 At the planned interim analysis (19.1 months), PFS was significantly improved in patients receiving penpulimab-kcqx compared to those receiving placebo (median of 9.6 versus 7.0 months, respectively).1, 4
The 24-month survival rate was 66.3% in the penpulimab-kcqx group and 61.9% in placebo group.4 A total of 97 deaths occurred, with 48 in the penpulimab-kcqx group and 49 in the placebo group.4 Median OS was not yet reached for either group, and the OS data were immature.1, 4 The BICR-assessed overall response rate was 68.1% in the penpulimab-kcqx group and 63.9% in the placebo group.4 The BICR-assessed median duration of response was 9.8 months in the penpulimab-kcqx group and 5.7 months in the placebo group.4
Recurrent Metastatic Non-Keratinizing Nasopharyngeal Carcinoma
Safety and efficacy of penpulimab-kcqx as a single agent for the treatment of previously treated unresectable or metastatic and non-keratinizing NPC were evaluated in an open-label, multicenter, multicohort, phase 2 trial (AK105-202).1, 5 Patients enrolled in the study had unresectable or metastatic NPC and received prior platinum-based chemotherapy and at least one other line of therapy for the treatment of recurrent or metastatic NPC or had disease progression within 6 months of completion of chemotherapy administered as neoadjuvant, adjuvant, or definitive chemoradiation treatment.1, 5 Patients received penpulimab-kcqx 200 mg IV once every 2 weeks, with 4 weeks per cycle, until disease progression, death, intolerable toxicities, voluntary withdrawal of consent, or a maximum of 24 months.1, 5 The primary efficacy outcomes were objective response rate and duration of treatment as evaluated by an independent radiological review committee using RECIST v1.1.1, 5
Among the 125 patients in the efficacy population, the median age was 50 years (range 21-66 years); 1.6% were 65 years of age or older, 76% were male, 100% were Asian, and 0% had an ECOG performance status of 0.1, 4, 5 Among these patients, 63% received 2 prior lines of chemotherapy, 37% received 3 or more prior lines of chemotherapy, and 92% received prior radiation therapy.1, 5 The objective response rate was 28%; 1 patient achieved complete response and 34 patients achieved a partial response.1, 5 The median duration of response was not reached at the time of data analysis.1 Among the 35 patients who had a complete or partial response, 83% had a duration of response of 6 months or more and 46% had a duration of response of 12 months or more.1, 4 At a median follow-up of 29.6 months, 48 (39.6%) deaths were reported.5 The 12- and 24-month OS rate was 66.1% and 48.6%, respectively.5 The median treatment duration was 4.1 months (range 0.03-40.9 months).5
The American Society of Clinical Oncology (ASCO) has published guidelines for the management of recurrent and metastatic head and neck cancers.6 According to the guidelines, a platinum-based dual chemotherapy regimen (gemcitabine with cisplatin) is generally considered the standard first-line treatment for patients with recurrent or metastatic NPC.6, 7 ASCO recommends the use of toripalimab, camrelizumab (not commercially available in the US), or tislelizumab in combination with gemcitabine and cisplatin as the first line treatment for patients with recurrent or metastatic NPC.6 If these drugs are unavailable, then pembrolizumab or nivolumab may be offered with gemcitabine and cisplatin.6 The ASCO guideline also states that PD-1 inhibitors may be offered to patients with recurrent or metastatic NPC who have progressed following platinum-based therapy; however, the strength of evidence for this recommendation is weak and based on informal consensus.6 Penpulimab-kcqx is not included in the ASCO guidelines because it was approved after guideline publication.8
Meta-analyses and systematic reviews evaluating the use of immune checkpoint inhibitors (including anti-PD-L1 antibodies) in the treatment of recurrent or metastatic NPC have found that the combination of an immune checkpoint inhibitor and chemotherapy is superior in terms of survival compared to chemotherapy as first-line treatment for recurrent or metastatic NPC regardless of PD-L1 expression status.9, 10, 11 The current evidence suggests that there is no single standard maintenance regimen following treatment with chemotherapy with or without anti-PD-1 antibodies and that an anti-PD-1 antibody or capecitabine may be considered in patients with recurrent or metastatic NPC.13
Administer penpulimab-kcqx by IV infusion.1
The drug is supplied in a single-dose vial as a 10-mg/mL injection concentrate that must be diluted prior to administration.1
Store unopened vials at 2-8°C in the original carton to protect from light; do not freeze.1
Do not shake the vial.1
Administer penpulimab-kcqx via an IV line containing a sterile, non-pyrogenic, low-protein binding 0.2 to 0.22 micron in-line or add-on filter.1
Do not administer other medications through the same IV line.1
Withdraw the required volume of penpulimab-kcqx and inject slowly into an IV bag containing 100 mL or less of 0.9% sodium chloride injection; the final concentration should be 2-5 mg/mL.1 Do not shake the diluted solution; mix the solution by gentle inversion.1
Penpulimab-kcqx does not contain a preservative; discard any unused solution.1
Following preparation, administer the diluted solution immediately.1 If not administered immediately, the diluted solution may be stored up to 4 hours either at room temperature (20-25°) or in the refrigerator (2-8°C); do not freeze.1 The total time from dilution to the end of the infusion should not exceed 4 hours.1 Discard the solution after 4 hours.1
Administer the diluted solution by IV infusion over 60 minutes.1 If mild or moderate infusion-related reactions occur, interrupt or slow the rate of infusion.1
Nasopharyngeal Carcinoma (NPC)
First-Line Treatment of Recurrent or Metastatic Non-Keratinizing NPC with Cisplatin or Carboplatin and Gemcitabine
The recommended adult dosage of penpulimab-kcqx, in combination with either cisplatin or carboplatin and gemcitabine, for the treatment of recurrent or metastatic NPC is 200 mg once every 3 weeks as an IV infusion until disease progression or unacceptable toxicity, for a maximum of 24 months.1 The order of administration is as follows: penpulimab-kcqx first, gemcitabine second, and cisplatin or carboplatin last.1 After penpulimab-kcqx, administer gemcitabine 1000 mg/m2 IV every 3 weeks for 6 cycles followed by cisplatin 80 mg/m2 IV or carboplatin AUC 5 IV every 3 weeks for 6 cycles.1
Recurrent Metastatic Non-Keratinizing NPC
The recommended adult dosage of penpulimab-kcqx as a single agent for the treatment of recurrent metastatic non-keratinizing NPC is 200 mg once every 2 weeks as an IV infusion until disease progression or unacceptable toxicity, for a maximum of 24 months.1
Dosage Modifications for Adverse Reactions
If adverse reactions occur, dosage reductions of penpulimab-kcqx are not recommended.1
In general, withhold penpulimab-kcqx for severe (grade 3) immune-mediated adverse reactions.1 Permanently discontinue therapy for life-threatening (grade 4) immune-mediated adverse reactions, recurrent severe (grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or if unable to reduce corticosteroid dose to ≤10 mg of prednisone or equivalent per day within 12 weeks of steroid initiation.1
Dosage modifications for adverse reactions that require different management from the general guidelines stated above are outlined in Table 1.1
Adverse Reactions and Severity | Dosage Modification |
|---|---|
Pneumonitis | Grade 2: Withholda Grade 3 or 4: Permanently discontinue |
Colitis | Grade 2 or 3: Withholda Grade 4: Permanently discontinue |
Hepatitis with no tumor involvement of the liver | AST or ALT increases to >3 and up to 8 times ULN or total bilirubin increases to >1.5 and up to 3 times ULN: Withholda AST or ALT increases to >8 times ULN or total bilirubin increases to >3 times ULN: Permanently discontinue |
Hepatitis with tumor involvement of the liver | Baseline AST or ALT is >1 and up to 3 times ULN and increases to >5 and up to 10 times ULN or baseline AST or ALT is >3 and up to 5 times ULN and increases to >8 and up to 10 times ULN: Withholda AST or ALT increases to >10 times ULN or total bilirubin increases to >3 times ULN: Permanently discontinue If baseline AST and ALT are less than or equal to ULN at baseline in patients with tumor involvement of the liver, withhold or permanently discontinue based on recommendations for hepatitis with no liver involvement |
Endocrinopathies | Grade 3 or 4: Withhold until clinically stable or permanently discontinue depending on severitya |
Nephritis with Renal Dysfunction | Grade 2 or 3 increased blood creatinine: Withholda Grade 4 increased blood creatinine: Permanently discontinue |
Exfoliative dermatologic conditions | Suspected SJS, TEN, or DRESS: Withholda Confirmed SJS, TEN, or DRESS: Permanently discontinue |
Myocarditis | Grade 2, 3, or 4: Permanently discontinue |
Neurological Toxicities | Grade 2: Withholda Grade 3 or 4: Permanently discontinue |
Infusion-related reactions | Grade 1 or 2: Interrupt or slow the rate of infusion Grade 3 or 4: Permanently discontinue |
aResume in patients with complete or partial resolution (grade 0 or 1) after corticosteroid taper. Permanently discontinue if no resolution within 12 weeks of steroid initiation or inability to reduce prednisone to less than or equal to 10 mg daily (or equivalent) within 12 weeks of initiating steroids.
The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.1
The manufacturer makes no specific dosage recommendations for patients with renal impairment.1
The manufacturer makes no specific dosage recommendation for geriatric patients.1
Immune-Mediated Adverse Reactions
Penpulimab-kcqx removes inhibition of the immune response; this may break peripheral tolerance and induce immune-mediated adverse reactions.1 Severe and fatal immune-mediated adverse reactions may occur in any organ system or tissue; reactions affecting more than one body system can occur simultaneously, and may occur at any time after penpulimab-kcqx initiation.1 Reactions generally occur during treatment but may occur after the drug is discontinued.1
Early identification and management of immune-mediated adverse reactions are necessary to ensure safe use of penpulimab-kcqx.1 Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions.1 Assess liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment.1 If suspected immune-mediated reactions occur, initiate appropriate workup to exclude alternative causes (including infection).1 Medically manage immune-mediated adverse reactions promptly and refer patient for specialty consultation as appropriate.1
Withhold or permanently discontinue penpulimab-kcqx depending on severity of the reaction.1 If penpulimab-kcqx treatment interruption or discontinuation is required, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to grade 1 or less, then initiate corticosteroid taper and continue to taper over 1 month or longer.1 Consider administration of other systemic immunosuppressants if the reaction is not controlled with corticosteroid therapy.1 Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies, dermatologic reactions) are discussed below.1
Penpulimab-kcqx may cause immune-mediated pneumonitis.1 In patients treated with other PD-1/PD-L1 blocking antibodies, the incidence of pneumonitis is higher in patients with a history of prior thoracic radiation.1
In patients receiving penpulimab-kcqx in combination with cisplatin or carboplatin and gemcitabine, immune-mediated pneumonitis occurred in 0.7% (1/146) of patients, including grade 2 (0.7%) reactions.1 Systemic corticosteroids were required in the single patient with pneumonitis and penpulimab-kcqx therapy was withheld.1
When used as a single agent, immune-mediated pneumonitis occurred in 1.3% (5/372) of patients, including grade 3 (0.5%), grade 2 (0.5%), and grade 1 (0.3%) reactions.1 Systemic corticosteroids were required in 80% of patients with pneumonitis.1 Pneumonitis led to permanent discontinuation of therapy in 0.8% of the overall 372 patients, and resolved in 20% of the 5 patients in which it was reported.1
Penpulimab-kcqx can cause immune-mediated colitis.1 Cytomegalovirus infection/reactivation has occurred in patients with corticosteroid-refractory immune-mediated colitis.1 In patients with corticosteroid-refractory colitis, consider repeating an infectious workup to exclude alternative etiologies.1
Immune-mediated colitis has been reported in 1.1% (4/372) of patients receiving penpulimab-kcqx as a single agent, including grade 2 (0.8%) and grade 1 (0.3%) reactions; colitis led to treatment interruption in 0.8% (3/372) of patients.1
Penpulimab-kcqx may cause immune-mediated hepatitis.1, 1
In patients receiving penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine, immune-mediated hepatitis occurred in one out of 146 (0.7%) as a grade 2 adverse reaction that required the use of systemic corticosteroids and withholding penpulimab-kcqx.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%) reactions.1 Hepatitis led to permanent discontinuation in 0.3% of patients and penpulimab-kcqx was withheld in 2.2% of patients.1 Hepatitis resolved in 64% of patients.1
Penpulimab-kcqx can cause primary and secondary adrenal insufficiency.1 If grade 2 or higher adrenal insufficiency occurs, initiate symptomatic treatment, including hormone replacement therapy as clinically indicated.1 Withhold or permanently discontinue penpulimab-kcqx depending on severity.1
Penpulimab-kcqx can cause immune-mediated hypophysitis, which may present with acute symptoms associated with mass effect (e.g., headache, photophobia, visual field cuts).1 Hypophysitis may lead to hypopituitarism.1 If hypophysitis occurs, initiate hormone replacement therapy as clinically indicated.1 Withhold or permanently discontinue penpulimab-kcqx depending on severity.1
Penpulimab-kcqx can cause immune-mediated thyroid disorders.1 Thyroiditis may present with or without endocrinopathy.1 Hypothyroidism may follow hyperthyroidism.1 If an immune-mediated thyroid disorder occurs, initiate hormone replacement therapy or medical management of hyperthyroidism as clinically indicated.1 Withhold or permanently discontinue penpulimab-kcqx based on severity.1
In patients using penpulimab-kcqx in combination with cisplatin or carboplatin and gemcitabine, hyperthyroidism occurred in 2.1% (3/146) of patients, including grade 2 (0.7%) and grade 1 (1.4%) reactions.1 Hypothyroidism occurred in 16% (26/146) of patients receiving penpulimab-kcqx in combination with cisplatin or carboplatin and gemcitabine, including grade 2 (13%) and grade 1 (4.8%) reactions; penpulimab-kcqx was withheld in 0.7% and resolved in 12% of patients.1
When used as a single agent, thyroiditis occurred in 0.5% (2/372) of patients receiving penpulimab-kcqx, including grade 2 (0.3%) and grade 1 (0.3%) reactions.1 Penpulimab-kcqx was withheld in 0.3% and thyroiditis resolved in 50% of patients.1 Hyperthyroidism occurred in 7% (24/372) of patients receiving penpulimab-kcqx, including grade 2 (1.1%) and grade 1 (5%) reactions; penpulimab-kcqx was withheld in 0.5% and resolved in 79% of patients.1 Hypothyroidism occurred in 19% (69/372) of patients receiving penpulimab-kcqx; the drug was withheld in 1.6% and resolved in 48% of patients.1
Type 1 diabetes has been reported 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%) reactions.1 Penpulimab-kcqx was permanently discontinued in 0.7%, withheld in 0.7%, and resolved in 75% of patients.1 Type 1 diabetes mellitus occurred in 0.8% (3/372) of patients receiving penpulimab-kcqx as a single agent, including grade 1 (0.8%) reactions; diabetes resolved in 67% of patients.1
Monitor patients for hyperglycemia or other signs and symptoms of diabetes and initiate insulin therapy as clinically indicated.1 Depending on severity, penpulimab-kcqx can be withheld.1
Nephritis with Renal Dysfunction
Penpulimab-kcqx can cause immune-mediated nephritis.1
When used as a single agent, nephritis occurred in 0.5% (2/372) of patients receiving penpulimab-kcqx, including grade 3 (0.3%) reactions; penpulimab-kcqx was permanently discontinued in 0.5%, systemic corticosteroids were required in 50%, and nephritis resolved in 50% of patients.1
Dermatologic Adverse Reactions
Penpulimab-kcqx can cause immune-mediated rash or dermatitis.1 Bullous and exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), has occurred with anti-PD-1/PD-L1 monoclonal antibodies.1 For treatment of mild to moderate non-exfoliative rashes, topical emollients and/or topical corticosteroids may be adequate.1 Withhold or permanently discontinue penpulimab-kcqx depending on severity.1
In patients receiving penpulimab-kcqx in combination with cisplatin or carboplatin and gemcitabine, dermatologic adverse reactions occurred 10% (14/146) of patients, including grade 3 (0.7%), grade 2 (4.8%), and grade 1 (4.1%) adverse reactions.1 Systemic corticosteroids were required in 36%; penpulimab-kcqx was withheld in 1.6%.1 Dermatologic adverse reactions resolved in 78.6% of patients.1
When used as a single agent, immune-mediated dermatologic adverse reactions occurred in 12% (43/372) of patients receiving penpulimab-kcqx, including grade 3 (1.3%), grade 2 (3.5%), and grade 1 (7%) reactions.1 Penpulimab-kcqx was withheld in 1.6% of patients and systemic corticosteroids were required in 14% of patients.1 Dermatologic adverse reactions resolved in 58% of patients.1
Other Immune-mediated Adverse Reactions
Other clinically important immune-mediated adverse reactions have been observed rarely with penpulimab-kcqx (or other anti-PD/PD-L1 monoclonal antibodies); in some instances, these reactions were severe or fatal.1
Specific reactions have included cardiac/vascular disorders (myocarditis, pericarditis, vasculitis); nervous system (meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis [including exacerbations], Guillain-Barre syndrome, nerve paresis, autoimmune neuropathy, nerve injury); ocular disorders (uveitis, iritis, and other ocular inflammatory toxicities); GI disorders (pancreatitis, gastritis, duodenitis); musculoskeletal disorders (myositis/polymyositis, rhabdomyolysis and associated sequelae, arthritis, polymyalgia rheumatica, dermatomyositis); hypoparathyroidism; and other hematologic /immune disorders (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
Some cases of ocular adverse reactions may 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.1
Penpulimab-kcqx can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis.1
In patients receiving penpulimab-kcqx in combination with cisplatin or carboplatin and gemcitabine, infusion-related reactions have been reported in 3.4% of patients, including grade 2 (1.4%) and grade 1 (2.1%) reactions.1
When used as a single agent, infusion-related reactions occurred in 10% of patients receiving penpulimab-kcqx, including grade 4 (0.3%), grade 3 (0.3%), grade 2 (6%), and grade 1 (3.8%) reactions; penpulimab-kcqx was withheld in 0.8% and permanently discontinued in 0.3% of patients.1
Monitor patients for signs and symptoms of infusion-related reactions (e.g., rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever).1 For mild (grade 1) or moderate (grade 2) infusion-related reactions, interrupt or slow the rate of infusion.1 For severe (grade 3) or life-threatening (grade 4) infusion-related reactions, stop the infusion and permanently discontinue penpulimab-kcqx.1
Complications of Allogeneic Hematopoietic Stem Cell Transplantation
Serious or fatal complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after treatment with an anti-PD-1/PD-L1 antibody.1 Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome without an identified infectious cause.1 Complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT.1
Closely monitor patients for evidence of transplant-related complications and intervene promptly.1 Weigh the benefits versus risks of penpulimab-kcqx prior to or after allogeneic HSCT.1
Fetal/Neonatal Morbidity and Mortality
Penpulimab-kcqx may cause fetal harm if administered to a pregnant women based on its mechanism of action and findings from animal studies.1 Inhibition of the PD-1/PD-L1 pathway in animals has been shown to increase the risk of immune-mediated rejection of the developing fetus, resulting in fetal death.1
Perform pregnancy testing in females of reproductive potential prior to initiating penpulimab-kcqx.1 Advise pregnant women of the potential risk to a fetus.1 Females of reproductive potential should use effective contraception during treatment with penpulimab-kcqx and for 4 months after the last dose.1
In controlled studies, treatment-emergent anti-drug antibodies (ADA) were detected in 24% of patients receiving penpulimab-kcqx in combination with gemcitabine and cisplatin or carboplatin and in 30% of patients receiving penpulimab-kcqx alone.1 Due to the low incidence of ADAs, the effects of these antibodies on the safety, efficacy, pharmacokinetics, and/or pharmacodynamics of penpulimab-kcqx are unknown.1
Penpulimab-kcqx can cause fetal harm if administered to a pregnant woman based on its mechanism of action and findings from animal reproductive studies.1, 1 There are no available human data on penpulimab-kcqx use during pregnancy.1 In animal studies, inhibition of the PD-1/PD-L1 pathway has been shown to increase the risk of immune-mediated rejection of the developing fetus, resulting in fetal death.1 Since human immunoglobulin G4 (IgG4) is known to cross the placenta, penpulimab-kcqx has the potential to be transmitted from the mother to the developing fetus.1
Advise pregnant women of the potential risk to a fetus.1
It is not known whether penpulimab-kcqx is distributed into human milk, or if the drug has any effects on the breastfed infant or on milk production.1 Maternal immunoglobulin G is known to be distributed into human milk.1 The effects of local GI exposure and limited systemic exposure of penpulimab-kcqx in the breast-fed infant are unknown.1 Because of the potential for serious adverse reactions in breast-fed infants, advise women to not breast-feed during treatment with penpulimab-kcqx and for 4 months after the last dose. 1
Females and Males of Reproductive Potential
Fetal harm may occur with the use of penpulimab-kcqx.1 Before initiating penpulimab-kcqx therapy in females of reproductive potential, verify that the patient is not pregnant.1 Advise females of reproductive potential to use effective contraception during treatment and for 4 months after the last dose of the drug.1
Safety and efficacy of penpulimab-kcqx have not been established in pediatric patients.1
Penpulimab-kcqx has not been adequately studied in patients 65 years of age and older to determine whether pharmacokinetics of the drug are affected by age.1 Of the 146 patients treated with penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine for NPC, 10% of patients were ≥65 years of age and 0.7% were ≥75 years of a there were insufficient numbers of patients ≥65 years of age to determine whether there are any differences in safety or effectiveness between younger and older patients.1
Of the 372 patients treated with penpulimab-kcqx as a single agent for NPC, 19% were ≥65 years of age and 7% were ≥75 years of a no overall differences in safety or effectiveness were observed between older and younger patients.1
No clinically significant differences in the pharmacokinetics of penpulimab-kcqx have been observed in patients with mild or moderate hepatic impairment.1 Penpulimab-kcqx has not been adequately studied in patients with severe hepatic impairment.1
No clinically significant differences in the pharmacokinetics of penpulimab-kcqx have been observed in patients with mild or moderate renal impairment.1 Penpulimab-kcqx has not been adequately studied in patients with severe renal impairment.1
The most common adverse effects of penpulimab-kcqx (≥20%) when used in combination with either cisplatin or carboplatin and gemcitabine were nausea, vomiting, hypothyroidism, constipation, decreased appetite, decreased weight, cough, COVID-19 infection, fatigue, rash, and pyrexia.1
The most common adverse effects of penpulimab-kcqx (≥20%) when used as a single agent were anemia and hypothyroidism.1
Penpulimab-kcqx is a humanized anti-programmed-death receptor-1 (anti-PD-1) monoclonal antibody; the drug is an IgG4 kappa immunoglobulin.1 Penpulimab-kcqx binds to the PD-1 receptor, an immune-checkpoint receptor expressed on activated T cells, monocytes, B cells, natural killer (NK) T cells, and dendritic cells.14 Overexpression of PD-1 ligands on the surface of tumor cells results in activation of PD-1 and suppression of cytotoxic T-cell activity.1, 14 Penpulimab-kcqx blocks the interaction between the PD-1 receptor and its ligands PD-L1 and PD-L2, resulting in enhanced immune response, including an enhanced antitumor response.1, 4
Penpulimab-kcqx differs from other anti-PD-1 monoclonal antibodies since it was designed to eliminate Fc receptor-mediated effector function, which may help prevent antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP)-mediated depletion of PD-1 expressing T lymphocytes thereby possibly preserving maximal anti-tumor activity of lymphocytes.4, 15 Penpulimab-kcqx may also be associated with a reduction in immune-related adverse events mediated by proinflammatory cytokines like IL-6 and IL-8 because of the Fc mutation.4
The exposure-response relationship and time course of pharmacodynamic response of penpulimab-kcqx have not been fully characterized.1 Penpulimab-kcqx concentrations increased proportionally over the dose range of 1-10 mg/kg after the first dose and steady state was reached by week 15.1 The mean terminal half-life was 32 days.1 Penpulimab-kcqx is expected to be metabolized into small peptides by catabolic pathways.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
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.
Penpulimab-kcqx is only available at select specialty pharmacies.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection concentrate, for IV use | 10 mg/mL | Penpulimab-kcqx | Akeso Biopharma |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions May 10, 2026. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Akeso Biopharma, Co., Ltd. Penpulimab-kcqx® (Penpulimab) INTRAVENOUS prescribing information. 2025 Apr.
2. US Food and Drug Administration. Search orphan drug designations and approvals. From FDA website. [Web]
3. Hu C, Chen X, Xu T, et al. Abstract CT011: Penpulimab versus placebo in combination with chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma: A global, multicenter, randomized, double-blind, phase 3 trial (AK105-304). Cancer Research. 2025 Apr 25;85(8_Supplement_2):CT011. [Web]
4. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Application Number 761258Orig1s000. Trade Name: penpulimab-kcqx. NDA/BLA Multi-disciplinary review and evaluation. [Web]
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