Toripalimab-tpzi, a humanized anti-programmed-death receptor-1 (anti-PD-1) monoclonal antibody, is an antineoplastic agent.1
Toripalimab-tpzi is used in combination with cisplatin and gemcitabine for the first-line treatment of adults with metastatic or with recurrent, locally advanced nasopharyngeal carcinoma (NPC).1 Toripalimab-tpzi is also used as a single agent for the treatment of adults with recurrent unresectable or metastatic NPC with disease progression on or after platinum-containing chemotherapy.1 Toripalimab-tpzi has been designated an orphan drug by FDA for the treatment of NPC.7
First-line Treatment of Metastatic or Recurrent, Locally Advanced NPC with Cisplatin and Gemcitabine
Safety and efficacy of toripalimab for the treatment of metastatic or recurrent locally advanced NPC have been established in a randomized, multicenter, single region, double-blind, placebo-controlled trial (JUPITER-02).1, 2 A total of 289 patients 18 to 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 toripalimab-tpzi or placebo in combination with gemcitabine and cisplatin once every 3 weeks for up to 6 cycles, followed by toripalimab-tpzi or placebo maintenance once every 3 weeks.1, 2 During the chemotherapy phase, patients received toripalimab 240 mg IV or placebo on day 1, gemcitabine 1000 mg/m2 on days 1 and 8, and cisplatin 80 mg/m2 on day 1 of each 3-week cycle for up to 6 cycles.1, 2 During the maintenance phase, patients continued to receive toripalimab 240 mg or placebo once every 3 weeks until progressive disease, intolerable toxicity, withdrawal of consent, or a maximum of 2 years of treatment.1, 2 The primary efficacy outcome measure was progression-free survival as evaluated by a blinded independent review committee according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1).1, 2
Among the patients enrolled in JUPITER-02, the median age was 48 years (range 19-72 years); 4.8% were 65 years of age or older, 83% were male, 100% were Asian, 57% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0, and 86% had metastatic disease at study entry.1 At the planned interim analysis, patients receiving toripalimab had a longer progression-free survival compared to those receiving placebo (median of 11.7 versus 8 months).1, 2 The median overall survival based on the final analysis was 33.7 months in the placebo group and was not reached in the toripalimab group.1 More patients receiving toripalimab had a complete response compared to patients receiving placebo (19% versus 11%).1
Previously Treated Unresectable or Metastatic NPC
Safety and efficacy of toripalimab for the treatment of previously treated unresectable or metastatic NPC have been established in an open label, multicenter, multicohort trial (POLARIS-02).1, 3 Patients enrolled in the study had unresectable or metastatic NPC and received prior platinum-based chemotherapy for the treatment of recurrent or metastatic NPC or had disease progression within 6 months of completion of platinum-based chemotherapy administered as neoadjuvant, adjuvant, or definitive chemoradiation treatment for locally advanced disease.1 Patients received toripalimab 3 mg/kg IV once every 2 weeks until disease progression, intolerable toxicity, or voluntary withdrawal of informed consent.1, 3 The primary efficacy outcome measures were confirmed overall response rate and duration of response as evaluated by a blinded independent review committee using RECIST 1.1.1, 3
Among the 172 patients enrolled in POLARIS-02, the median age was 45 years (range 22-68 years); 4.1% were 65 years of age or older, 83% were male, 100% were Asian, and 37% had an ECOG performance status of 0.1 Patients received a median of 2 prior systemic therapies for recurrent/metastatic disease, and 95% of patients had metastatic disease.1 The overall response rate was 21% and the median duration of response was 14.9 months.1 The complete response rate was 2.3% and the partial response rate was 19%.1 One year after the last patient enrollment, 49.5% of patients died, 41.1% of patients stopped treatment, and 9.5% of patients remained on treatment; the median treatment duration was 3.7 months (range 0.2-34.8 months).3
The American Society of Clinical Oncology (ASCO) has published guidelines for the management of recurrent and metastatic head and neck cancers.4 A platinum-based dual chemotherapy regimen (gemcitabine with cisplatin) is generally considered the standard first-line treatment for patients with recurrent or metastatic NPC.4, 5 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.4 If these drugs are unavailable, then pembrolizumab or nivolumab may be offered with gemcitabine and cisplatin.4 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.4 A meta-analysis found that progression-free survival was similar among the PD-1 inhibitors recommended in the ASCO guidelines (camrelizumab, tislelizumab, and toripalimab).5, 6
Toripalimab-tpzi is administered as an IV infusion.1 The drug is supplied in a single-dose vial as a 40 mg/mL injection concentrate that must be diluted prior to administration.1
Store the vial at 2-8°C in the original carton to protect from light; do not freeze.1
Do not shake the vial.1
Prior to use, store the diluted IV solution in the refrigerator at 2-8°C for up to 24 hours or at room temperature (20-25°C) for up to 8 hours, from the time of dilution to completion of the infusion.1 Discard the solution if not used within 8 hours if stored at room temperature or 24 hours if stored in the refrigerator.1 If the diluted solution is refrigerated, allow the solution to come to room temperature prior to administration.1
Administer toripalimab-tpzi via an infusion pump using an in-line aseptic 0.2 or 0.22 micron filter.1
Do not co-administer other medications through the same IV line.1
Withdraw the required volume of toripalimab-tpzi and inject slowly into a 100 mL or 250 mL infusion bag containing 0.9% sodium chloride injection; the final concentration should be 1-3 mg/mL.1 Do not shake the diluted solution; mix the solution by gentle inversion.1
Administer the first IV infusion over 60 minutes.1 If no infusion-related reactions occur, subsequent infusions may be administered over 30 minutes.1
Nasopharyngeal Carcinoma (NPC)
First-line Treatment of Metastatic or Recurrent, Locally Advanced NPC with Cisplatin and Gemcitabine
The recommended adult dosage of toripalimab-tpzi, in combination with cisplatin and gemcitabine, for the treatment of adults with metastatic or with recurrent locally advanced NPC is 240 mg once every 3 weeks as an IV infusion until disease progression, unacceptable toxicity, or up to 24 months.1
Previously Treated Unresectable or Metastatic NPC
The recommended adult dosage of toripalimab-tpzi for the treatment of recurrent unresectable or metastatic NPC with disease progression on or after a platinum-containing chemotherapy is 3 mg/kg as an IV infusion once every 2 weeks until disease progression or unacceptable toxicity.1
Dosage Modification for Adverse Reactions
If adverse reactions occur, dosage reductions of toripalimab-tpzi are not recommended.1
Generally, withhold toripalimab-tpzi for severe (grade 3) immune-mediated adverse reactions.1 Permanently discontinue therapy for life-threatening (grade 4) immune-mediated adverse reactions and recurrent severe (grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or if unable to reduce corticosteroid dose to ≤10 mg of prednisone 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 Reaction | Dosage Modification Based on Severity |
|---|---|
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 ≤8 times ULN OR total bilirubin increases to >1.5 and ≤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 | If baseline AST and ALT are ≤ULN at baseline in patients with liver involvement, withhold or permanently discontinue based on recommendations for hepatitis with no liver involvement Baseline AST or ALT is >1 and ≤3 times ULN and increases to >5 and ≤10 times ULN OR baseline AST or ALT is >3 and ≤5 times ULN and increases to >8 and ≤10 times ULN: Withholda Baseline AST or ALT is >ULN and increases to >10 times ULN OR total bilirubin increases to >3 times ULN: Permanently discontinue |
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: Stop infusion and permanently discontinue |
aResume in patients with complete or partial resolution (grade 0 to 1) after corticosteroid taper. Permanently discontinue if no resolution within 12 weeks of steroid initiation or inability to reduce prednisone 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 recommendations for geriatric patients.1
Severe and Fatal Immune-mediated Adverse Reactions
Toripalimab-tpzi 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 1 body system can occur simultaneously, and may occur at any time after toripalimab-tpzi initiation.1 Reactions generally occur during treatment but may also occur after the drug is discontinued.1
Early identification and management of immune-mediated adverse reactions are necessary to ensure safe use of toripalimab-tpzi.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 for specialty consultation as appropriate.1
Withhold or permanently discontinue toripalimab-tpzi depending on the severity of the reaction.1 If toripalimab-tpzi treatment interruption or discontinuation is required, administer systemic corticosteroids (1-2 mg/kg per day prednisone or equivalent) until improvement to grade 1 or less, then initiate corticosteroid taper and continue to taper over ≥1 month.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
Toripalimab-tpzi 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 toripalimab-tpzi in combination with cisplatin and gemcitabine, immune-mediated pneumonitis occurred in 2.1% (3/146) of patients, including grade 2 (1.4%) adverse reactions.1 Pneumonitis resolved in 67% of patients.1
When used as a single agent, immune-mediated pneumonitis occurred in 2.6% (22/851) of patients, including fatal (0.2%), grade 3 (0.7%), and grade 2 (1.1%) adverse reactions.1 Systemic corticosteroids were required in 82% of patients with pneumonitis.1 Pneumonitis led to permanent discontinuations in 1.2% of patients, and resolved in 23% of these patients.1
Toripalimab-tpzi 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 infectious workup to exclude alternative etiologies.1
Immune-mediated colitis has been reported in 0.4% (3/851) of patients receiving toripalimab-tpzi as a single agent, including grade 3 (0.2%) and grade 2 (0.1%) adverse reactions; colitis resolved in all 3 patients.1
Toripalimab-tpzi may cause immune-mediated hepatitis.1
In patients receiving toripalimab-tpzi in combination with cisplatin and gemcitabine, immune-mediated hepatitis occurred in one out of 146 (0.7%) patients; this was a grade 3 adverse reaction that required systemic corticosteroids.1
When used as a single agent, immune-mediated hepatitis occurred in 3.3% (28/851) of patients receiving toripalimab-tpzi, including grade 4 (0.8%), grade 3 (2.1%), and grade 2 (0.4%) adverse reactions.1 Hepatitis led to permanent discontinuation in 1.1% of patients and toripalimab-tpzi was withheld in 0.8% of patients.1 Hepatitis resolved in 54% of patients.1
Toripalimab-tpzi 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 toripalimab-tpzi depending on severity.1
When used as a single agent, adrenal insufficiency occurred in 0.5% (4/851) of patients, including grade 2 (0.4%) and grade 1 (0.1%) adverse reactions.1 Systemic corticosteroids were required in 75% of patients.1 Toripalimab-tpzi was withheld in 1 patient, and was reinitiated after symptom improvement.1
Toripalimab-tpzi 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 toripalimab-tpzi depending on severity.1
When used as a single agent, hypophysitis occurred in 0.4% (3/381) of patients receiving toripalimab-tpzi, including grade 3 (0.2%) and grade 2 (0.1%) adverse reactions.1 All 3 cases required systemic corticosteroids; hypophysitis led to permanent discontinuation of toripalimab-tpzi in 1 patient.1 Toripalimab-tpzi was withheld in 1 patient and was later reinitiated.1
Toripalimab-tpzi 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 toripalimab-tpzi based on severity.1
In patients using toripalimab-tpzi in combination with cisplatin and gemcitabine, thyroiditis occurred in 2.1% (3/146) of patients, including grade 2 (1.4%) reactions.1 All 3 patients required thyroid replacement therapy and thyroiditis resolved in 1 patient.1 Hyperthyroidism occurred in 1.4% (2/146) of patients receiving toripalimab-tpzi in combination with cisplatin and gemcitabine; both cases resolved.1 Hypothyroidism occurred in 30% (44/146) of patients receiving toripalimab-tpzi in combination with cisplatin and gemcitabine; 8% of patients required hormone replacement therapy.1 Toripalimab-tpzi was withheld in 3 patients and reinitiated in 2 patients.1
When used as a single agent, thyroiditis occurred in 0.6% (5/851) of patients receiving toripalimab-tpzi, including grade 2 reactions (0.1%).1 Two patients received systemic steroids and 2 patients received hormone replacement therapy; thyroiditis resolved in 2 patients.1 Hyperthyroidism occurred in 7% (55/851) of patients receiving toripalimab-tpzi and resolved in 47 patients.1 Hypothyroidism occurred in 15% (128/851) of patients receiving toripalimab-tpzi and 63% of these patients required thyroid hormone replacement.1 Toripalimab-tpzi was withheld in 4 patients and was reinitiated in 3 patients.1
Type 1 diabetes has been reported in 0.9% (8/851) of patients receiving toripalimab-tpzi, including grade 4 (0.1%), grade 3 (0.7%), and grade 2 (0.1%) reactions.1 Six patients required insulin therapy and 0.4% of patients permanently discontinued toripalimab-tpzi.1
Monitor patients for hyperglycemia or other signs and symptoms of diabetes during treatment with toripalimab-tpzi.1 Initiate insulin therapy as clinically indicated.1 Withhold toripalimab-tpzi depending on severity.1
Nephritis with Renal Dysfunction
Toripalimab-tpzi can cause immune-mediated nephritis.1
In patients receiving toripalimab-tpzi in combination with cisplatin and gemcitabine, nephritis occurred in 0.7% (1/146) of patients; this patient required systemic corticosteroids and the nephritis led to discontinuation of toripalimab-tpzi.1 Nephritis resolved in this patient.1
When used as a single agent, nephritis occurred in 0.5% (4/851) of patients receiving toripalimab-tpzi, including grade 3 (0.5%) adverse reactions; nephritis resolved in 75% of patients.1
Dermatologic Adverse Reactions
Toripalimab-tpzi can cause immune-mediated rash or dermatitis.1 Bullous and exfoliative dermatitis, including Stevens-Johnson syndrome, toxic epidermal necrolysis, 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 toripalimab-tpzi depending on severity.1
In patients receiving toripalimab-tpzi in combination with cisplatin and gemcitabine, dermatologic adverse reactions occurred in 8% (12/146) of patients, including grade 3 (3.4%) and grade 2 (1.4%) adverse reactions.1 Systemic corticosteroids were required in 25% of patients and 2.1% of patients permanently discontinued toripalimab-tpzi.1 Dermatologic adverse reactions resolved in 92% of patients.1
When used as a single agent, immune-mediated dermatologic adverse reactions occurred in 4% (34/851) of patients receiving toripalimab-tpzi, including grade 3 (0.4%), and grade 2 (1.4%) adverse reactions.1 Toripalimab-tpzi was withheld in 0.4% of patients and systemic corticosteroids were required in 12% of patients.1 Dermatologic adverse reactions resolved in 71% of patients.1
Other Immune-mediated Adverse Reactions
Other clinically important immune-mediated adverse reactions have been observed rarely with toripalimab-tpzi (or other anti-PD-1/PD-L1 monoclonal antibodies); in some instances, these reactions were severe or fatal.1
Specific reactions have included cardiac/vascular disorders (myocarditis, pericarditis, vasculitis); neurologic disorders (meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis [including exacerbation], Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy); ocular disorders (uveitis, iritis, 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
Toripalimab-tpzi can cause severe or life-threatening infusion-related reactions including hypersensitivity and anaphylaxis.1
In patients receiving toripalimab-tpzi in combination with cisplatin and gemcitabine, infusion-related reactions have been reported in 4.1% of patients, including grade 2 (0.7%) reactions.1
Infusion-related reactions have occurred in 2% of patients receiving toripalimab-tpzi as a single agent, including grade 3 (0.1%) and grade 2 (0.6%) reactions; toripalimab-tpzi was withheld in 1 patient.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 toripalimab-tpzi.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 toripalimab-tpzi therapy prior to or after an allogeneic HSCT.1
Toripalimab-tpzi may cause fetal harm if administered to a pregnant woman 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 toripalimab-tpzi.1 Advise pregnant women of the potential risk to a fetus.1 Advise females of reproductive potential to use effective contraception during treatment with toripalimab-tpzi and for 4 months after the last dose.1
In controlled studies, treatment-emergent anti-drug antibodies (ADA) were detected in 3.4% of patients when receiving toripalimab-tpzi in combination with gemcitabine and cisplatin for a median duration of 15.1 months, and in 3.7% of patients when receiving toripalimab-tpzi alone for a median duration of 3.3 months.1 Due to the low incidence of ADAs, the effects of these antibodies on the safety, efficacy, pharmacokinetics, and/or pharmacodynamics of toripalimab-tpzi are unknown.1
Toripalimab-tpzi may cause fetal harm if administered to a pregnant woman based on its mechanism of action and findings from animal reproductive studies.1 There are no available human data on toripalimab-tpzi 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, toripalimab-tpzi 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 toripalimab-tpzi 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 to toripalimab-tpzi 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 toripalimab-tpzi and for 4 months after the last dose.1
Females and Males of Reproductive Potential
Fetal harm may occur with use of toripalimab-tpzi.1 Before initiating toripalimab-tpzi 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.1
Safety and efficacy of toripalimab-tpzi have not been established in pediatric patients.1
Toripalimab-tpzi has not been adequately studied in patients 65 years of age and older to determine whether the pharmacokinetics are affected by age.1 Of the 851 patients treated with toripalimab-tpzi with tumor types including NPC, 171 (20%) patients were 65 years of age or older and 13 (1.5%) patients were 75 years of age or older; no overall differences in safety were observed between elderly and younger patients.1
No clinically significant differences in the pharmacokinetics of toripalimab-tpzi were observed in patients with mild hepatic impairment.1 Toripalimab-tpzi has not been adequately studied in patients with moderate or severe hepatic impairment.1
No clinically significant differences in the pharmacokinetics of toripalimab-tpzi were observed in patients with mild renal impairment.1 Toripalimab-tpzi has not been adequately studied in patients with moderate or severe renal impairment.1
The most common adverse reactions (≥20%) in patients receiving toripalimab-tpzi in combination with cisplatin and gemcitabine were nausea, vomiting, decreased appetite, constipation, hypothyroidism, rash, pyrexia, diarrhea, peripheral neuropathy, cough, musculoskeletal pain, upper respiratory infection, insomnia, dizziness, and malaise.1
The most common adverse reactions (≥20%) in patients receiving toripalimab-tpzi as a single agent were fatigue, hypothyroidism and musculoskeletal pain.1
Toripalimab-tpzi is a humanized anti-programmed-death receptor-1 (anti-PD-1) monoclonal antibody; the drug is an IgG4 kappa immunoglobulin.1 Toripalimab 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.8 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, 8 Toripalimab blocks the interaction between the PD-1 receptor and its ligands PD-L1 and PD-L2, resulting in an enhanced immune response, including an enhanced antitumor response.1, 6
The exposure-response relationship and time course of pharmacodynamic response of toripalimab have not been fully characterized.1 Toripalimab-tpzi concentrations increased non-linearly over the dose range of 0.3-10 mg/kg every 2 weeks and steady state was reached by week 7.1 The mean terminal half life was 10 ± 1.5 days after the first dose and 18 ± 9.4 days at steady state.1 Toripalimab 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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection concentrate, for IV infusion | 40 mg/mL | Loqtorzi® | Coherus BioSciences |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions June 10, 2025. 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. Coherus BioSciences, Inc.. LOQTORZI® (toripalimab) INTRAVENOUS prescribing information. Redwood City, CA; 2024 Oct.
2. Mai HQ, Chen QY, Chen D, et al. Toripalimab plus chemotherapy for recurrent or metastatic nasopharyngeal carcinoma: The JUPITER-02 randomized clinical trial. JAMA. 2023;330(20):1961-1970.
3. Wang FH, Wei XL, Feng J, et al. Efficacy, safety, and correlative biomarkers of toripalimab in previously treated recurrent or metastatic nasopharyngeal carcinoma: A phase II clinical trial (POLARIS-02). J Clin Oncol. 2021;39(7):704-712.
4. Yilmaz E, Ismaila N, Bauman JE, et al. Immunotherapy and biomarker testing in recurrent and metastatic head and neck cancers: ASCO Guideline. J Clin Oncol. 2023;41(5):1132-1146.
5. Sun H, Bu F, Li L, et al. Efficacy and safety of immune checkpoint inhibitors combined with chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma: A network meta-analysis of randomized controlled trials. Ann Pharmacother. 2024;58(4):349-359.
6. Food and Drug Administration. Center for Drug Evaluation and Research Application Number: 761240Orig1s000 Multi-Discipline Review. Revised 2022 April. From FDA website.
7. US Food and Drug Administration. Search orphan drug designations and approvals. From FDA website. Accessed 2025 Jan 4. [Web]
8. Shiravand Y, Khodadadi F, Kashani SMA et al. Immune checkpoint inhibitors in cancer therapy. Curr Oncol. 2022 Apr 24;29(5):3044-3060. . . [PubMed 35621637]