Dosing & Uses
Dosage Forms & Strengths
injectable solution
- 40mg/mL (6-mL single-dose vial)
Nasopharyngeal Carcinoma
Combination therapy
- Indicated in combination with cisplatin and gemcitabine for first-line treatment of metastatic or recurrent locally advanced nasopharyngeal carcinoma (NPC)
- 240 mg IV q3Weeks
- Continue until disease progression, unacceptable toxicity, or up to 24 months
Monotherapy
- Indicated as monotherapy for treatment of recurrent, unresectable, or metastatic NPC with disease progression on or after platinum-containing chemotherapy
- 3 mg/kg IV q2Weeks
- Continue until disease progression or unacceptable toxicity
Dosage Modifications
Note: No dosage reductions are recommended
Pneumonitis
- Grade 2: Withhold; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
- Permanently discontinue if complete or partial resolution does not occur within 12 weeks of initiating steroids, or prednisone dosage cannot be reduced to ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
- Grade 3 or 4: Permanently discontinue
Colitis
- Grade 2 or 3: Withhold; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
- Permanently discontinue if complete or partial resolution does not occur within 12 weeks of initiating steroids, or prednisone dosage cannot be reduced to ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
- Grade 4: Permanently discontinue
Hepatitis without liver tumor involvement
- Aspartate aminotransferase (AST) or alanine transaminase (ALT) increases to >3 and ≤8x upper limit of normal (ULN) or total bilirubin increases to >1.5 and <3x ULN: Withhold therapy; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
- Permanently discontinue if complete or partial resolution does not occur within 12 weeks of initiating steroids, or prednisone dosage cannot be reduced to ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
- AST or ALT increases to >8x ULN or total bilirubin increases to >3x ULN: Permanently discontinue
Hepatitis with tumor with liver involvement
-
Withhold therapy
- Baseline AST or ALT >1 and ≤3x ULN and increases to >5 and ≤10x ULN
- Baseline AST or ALT >3 and ≤5x ULN and increases to >8 and ≤10x ULN
- Resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
- Permanently discontinue if complete or partial resolution does not occur within 12 weeks of initiating steroids, or prednisone dosage cannot be reduced to ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
-
Permanently discontinue
- AST or ALT increases to >10x ULN or total bilirubin increases to >3x ULN
Endocrinopathies
- Grade 3 or 4: Withhold until clinically stable or permanently discontinue depending on severity
- Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
Nephritis with renal dysfunction
- Grade 2 or 3 increased blood creatinine: Withhold therapy; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
- Permanently discontinue if complete or partial resolution does not occur within 12 weeks of initiating steroids, or prednisone dosage cannot be reduced to ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
- Grade 4 increased blood creatinine: Permanently discontinue
Exfoliative dermatologic conditions
- Suspected Stevens-Johnson Syndrome (SJS), toxic epidermal necrosis (TEN), or Drug Rash with Eosinophilia and Systemic Symptoms (DRESS): Withhold therapy
- Confirmed SJS, TEN, or DRESS: Permanently discontinue
Myocarditis
- Grade 2, 3, or 4: Permanently discontinue
Neurologic toxicities
- Grade 2: Withhold therapy; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
- Permanently discontinue if complete or partial resolution does not occur within 12 weeks of initiating steroids, or prednisone dosage cannot be reduced to ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
- Grade 3 or 4: Permanently discontinue
Infusion-related reactions
- Grade 1 or 2: Interrupt or slow infusion rate
- Grade 3 or 4: Permanently discontinue
Renal impairment
- Mild (CrCl 60-89 mL/min): No dosage adjustment necessary
- Moderate or severe (CLCr 15-59 mL/min): Pharmacokinetics not studied
Hepatic impairment
- Mild (total bilirubin >1 to 1.5x ULN with any AST or total bilirubin ≤ULN with AST > ULN): No dosage adjustment necessary
- Moderate or severe (total bilirubin >1.5x ULN and any AST): Pharmacokinetics not studied
Dosing Considerations
Females of reproductive potential: Verify pregnancy status before initiating
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (1)
- etrasimod
etrasimod, toripalimab. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Risk of additive immune system effects with etrasimod has not been studied in combination with antineoplastic, immune-modulating, or noncorticosteroid immunosuppressive therapies. Avoid coadministration during and in the weeks following administration of etrasimod. .
Monitor Closely (0)
Minor (0)
Adverse Effects
>10%
All grades
- Decreased lymphocytes (52%)
- Decreased hemoglobin (43%)
- Decreased albumin (38%)
- Decreased sodium (35%)
- Decreased phosphate (32%)
- Increased aspartate aminotransferase (AST) (30%)
- Decreased calcium (29%)
- Increased alkaline phosphatase (28%)
- Hypothyroidism (27%)
- Increased triglycerides (26%)
- Increased glucose (24%)
- Increased alanine aminotransferase (ALT) (1.6%)
- Fatigue (22%)
- Cough (20%)
- Musculoskeletal pain (18%)
- Pyrexia (16%)
- Decreased appetite (13%)
- Constipation (11%)
- Pruritus (11%)
- Rash (11%)
- Decreased weight (11%)
Grade 3 or 4
- Decreased sodium (11%)
1-10%
Grade 3 or 4
- Decreased lymphocytes (9%)
- Decreased hemoglobin (6%)
- Increased AST (3.8%)
- Decreased phosphate (3.2%)
- Fatigue (2.6%)
- Increased alkaline phosphatase (2.2%)
- Increased ALT (1.6%)
- Musculoskeletal pain (1.1%)
- Decreased appetite (1.1%)
- Increased triglycerides (1.1%)
- Increased glucose (1.1%)
<1%
Grade 3 or 4
- Decreased albumin (0.5%)
- Decreased calcium (0.5%)
Warnings
Severe infusion-related reactions can occur; discontinue in patients with severe or life-threatening infusion reactions
May cause fetal harm when administered to pregnant females
In clinical trials in multiple myeloma patients, adding a PD-1 blocking antibody to a thalidomide analog plus dexamethasone resulted in increased mortality
Cytomegalovirus (CMV) infection/reactivation reported in patients with corticosteroid- refractory immune-mediated colitis; in cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies
Complication of allogeneic HSCT
- Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after treatment with a PD-1/PD-L1 blocking antibody
- Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause)
- These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT
- Monitor closely for evidence of transplant-related complications and intervene promptly
- Assess benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody before or after an allogeneic HSCT
Immune-mediated adverse reactions
- Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue and include immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, and dermatologic adverse reactions; evaluate liver enzymes and thyroid function at baseline and periodically during treatment
- Immune-mediated encephalitis can occur; withhold therapy in patients with new-onset moderate to severe neurologic signs or symptoms and evaluate to rule out infectious or other causes of those findings
- When combined with cisplatin and gemcitabine, immune-mediated nephritis may occur; reactions may be severe or fatal; monitor for early identification and management; evaluate creatinine at baseline and periodically during treatment
- Other clinically significant and potentially fatal immune-mediated adverse reactions (eg, myocarditis, rhabdomyolysis, myositis, uveitis, iritis, pancreatitis) can occur after discontinuation
-
Immune-mediated endocrinopathies
- Immune-mediated hypophysitis reported; monitor
- Immune-mediated hypothyroidism and hyperthyroidism reported; monitor for changes in thyroid function and initiate thyroid hormone replacement as needed; administer hormone-replacement therapy for hypothyroidism; initiate medical management for control of hyperthyroidism
- Adrenal insufficiency may occur; monitor for signs and symptoms of adrenal insufficiency during and after treatment
- May cause type 1 diabetes mellitus; monitor for hyperglycemia
-
Immune-mediated skin reactions
- May cause immune-mediated rash, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN); if symptoms or signs of SJS or TEN develop, withhold therapy and refer patient for specialized care for assessment and treatment
- Immune-mediated rash reported in combination with ipilimumab; withhold for severe rash and permanently discontinue for life-threatening rash
-
Immune-mediated colitis
- Therapy can cause immune-mediated colitis, defined as requiring use of corticosteroids and having no clear alternative etiology; common sign in definition of colitis reported to be diarrhea
Pregnancy & Lactation
Pregnancy
Based on its mechanism of action, fetal harm may occur when administered to pregnant females
No data are available on use of toripalimab in pregnant females
Human IgG4 immunoglobulins (IgG4) are known to cross the placenta; therefore, can potentially be transmitted from mother to developing fetus
Advise women of the potential risk to a fetus
Animal data
- Animal studies have demonstrated that inhibiting the PD1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of developing fetus and result in fetal death
Contraception
- Verify pregnancy status before initiating in females of reproductive potential
- Use effective contraception during treatment and for at least 4 months following last dose
Lactation
No data are available on presence of toripalimab in human milk or its effects on breastfed children or on milk production
Maternal IgG is known to be present in human milk
Effects of local gastrointestinal exposure and limited systemic exposure in breastfed children to toripalimab are unknown
Advise lactating women not to breastfeed during treatment and for 4 months after last dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Monoclonal antibody to programmed cell death–1 protein (PD-1); blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2
PD-1 and PD-L1
- PD-1 and related target PD-ligand 1 (PD-L1) are expressed on the surface of activated T-cells under normal conditions; PD-1/PD-L1 interaction inhibits immune activation and reduces T-cell cytotoxic activity when bound
- This negative feedback loop is essential for maintaining normal immune responses and limits T-cell activity to protect normal cells during chronic inflammation
- Tumor cells may circumvent T-cell-mediated cytotoxicity by expressing PD-L1 on the tumor itself or on tumor-infiltrating immune cells, resulting in the inhibition of immune-mediated killing of tumor cells
Absorption
Steady-state reached at Week 7
Distribution
Vss: 3.7 L
Metabolism
Expected to be metabolized into small peptides by catabolic pathways
Elimination
Clearance: 14.9 L/hr (first dose); 9.5 L/hr (steady-state)
Half-life: 10 days (first dose); 18 days (steady-state)
Administration
IV Compatibility
0.9% NaCl
Polypropylene infusion bags and infusion sets with 0.2- or 0.22-micron inline filter
IV Preparation
Preparation for Intravenous Infusion
Visually inspect vial for particulate matter and discoloration; solution is clear to slightly opalescent, colorless to slightly yellow; discard if visible particles observed
Withdraw required volume and inject slowly into a 10-mL or 250-mL 0.9 NaCl infusion bag
Mix diluted solution by gentle inversion; do not shake; final concentration of diluted solution is 1-3 mg/mL
Discard any unused portion left in vial
IV Administration
Administer IV via an infusion pump using a 0.2- or 0.22- micron inline filter
First infusion: Infuse over at least 60 min
Subsequent infusions: If no infusion-related reactions occurred during first infusion, may be administered over 30 min
Do not coadminister other drugs through same IV line
When administered on same day as chemotherapy, administer before chemotherapy
Storage
Unopened vials
- Refrigerate at 2-8°C (36-46°F) in original carton to protect from light
- Do not freeze
- Do not shake
Diluted solution
- Contains no preservatives
- If not administered immediately, store either at room temperature, 20-25°C (68- 77°F) for ≤8 hr, or refrigerate at 2-8°C (36-46°F) for ≤24 hr from time of dilution to infusion completion
- If refrigerated, allow diluted solution to come to room temperature before administering
- Discard diluted solution stored at room temperature after 8 hr or if refrigerated after 24 hr
- Do not freeze
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Formulary
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