Loqtorzi
(Toripalimab-Tpzi)Dosage & Administration
In combination with cisplatin and gemcitabine:
As a single agent:
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Loqtorzi Prescribing Information
Warnings and Precautions (
LOQTORZI is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Important immune-mediated adverse reactions listed under WARNINGS AND PRECAUTIONS may not include all possible severe and fatal immune-mediated reactions.
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time after starting PD-1/PD-L1 blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of PD-1/PD-L1 blocking antibodies.
Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Monitor closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.
Withhold or permanently discontinue LOQTORZI depending on severity
Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.
LOQTORZI in combination with cisplatin and gemcitabine can cause immune-mediated pneumonitis. In patients treated with other PD-1/PD-L1 blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 2.1% (3/146) of patients receiving LOQTORZI, including Grade 2 (1.4%) adverse reactions. Pneumonitis resolved in 67% (2/3) of these patients.
LOQTORZI can cause immune-mediated pneumonitis. In patients treated with other PD-1/PD-L1 blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 2.6% (22/851) of patients receiving LOQTORZI, including fatal (0.2%), Grade 3 (0.7%), and Grade 2 (1.1%) adverse reactions. Systemic corticosteroids were required in 82% (18/22) of patients with pneumonitis. Pneumonitis led to permanent discontinuation of LOQTORZI in 1.2% (10/851) of patients. Pneumonitis resolved in 23% (5/22) of these patients.
LOQTORZI can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.
Immune-mediated colitis occurred in 0.4% (3/851) of patients receiving LOQTORZI, including Grade 3 (0.2%) and Grade 2 (0.1%) adverse reactions. Colitis resolved in all 3 patients.
LOQTORZI in combination with cisplatin and gemcitabine can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (1/146) of patients receiving LOQTORZI in combination with cisplatin and gemcitabine, which was a Grade 3 (0.7%) adverse reaction. The patient with immune-mediated hepatitis required systemic corticosteroids.
LOQTORZI can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 3.3% (28/851) of patients receiving LOQTORZI, including Grade 4 (0.8%), Grade 3 (2.1%), and Grade 2 (0.4%) adverse reactions. Hepatitis led to permanent discontinuation of LOQTORZI in 1.1% of patients and withholding of LOQTORZI in 0.8% of patients. Hepatitis resolved in 54% (15/28) of these patients.
LOQTORZI can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold or permanently discontinue LOQTORZI depending on severity
Adrenal insufficiency occurred in 0.5% (4/851) of the patients receiving LOQTORZI, including Grade 2 (0.4%) and Grade 1 (0.1%) adverse reactions
LOQTORZI can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effects such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue LOQTORZI depending on severity
Hypophysitis occurred in 0.4% (3/851) of patients receiving LOQTORZI, including Grade 3 (0.2%) and Grade 2 (0.1%) adverse reactions. All three patients received systemic corticosteroids. Hypophysitis led to permanent discontinuation of LOQTORZI in 0.1% (1/851) of patients and withholding of LOQTORZI in 0.1% (1/851) of patients. The one patient in whom LOQTORZI was withheld reinitiated LOQTORZI.
LOQTORZI can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue LOQTORZI depending on severity
Thyroiditis occurred in 2.1% (3/146) of patients receiving LOQTORZI in combination with cisplatin and gemcitabine, including Grade 2 (1.4%). Three patients required thyroid hormone replacement therapy. Thyroiditis resolved in one of the 3 patients.
Hyperthyroidism occurred in 1.4% (2/146) of patients receiving LOQTORZI in combination with cisplatin and gemcitabine. Hyperthyroidism resolved in these 2 patients.
Hypothyroidism occurred in 30% (44/146) of patients receiving LOQTORZI in combination with cisplatin and gemcitabine, including Grade 2 (24%) and Grade 1 (6%). Eighty percent of the 44 patients required thyroid hormone replacement therapy. LOQTORZI was withheld in 2.1% (3/146) of the patients. Of the 3 patients in whom LOQTORZI was withheld, 2 patients reinitiated LOQTORZI.
Thyroiditis occurred in 0.6% (5/851) of patients receiving LOQTORZI, including Grade 2 (0.1%). Two of these 5 patients received systemic corticosteroids and 2 required thyroid hormone replacement therapy. Thyroiditis resolved in 2 of the 5 patients.
Hyperthyroidism occurred in 7% (55/851) of patients receiving LOQTORZI, including Grade 2 (1.9%). Hyperthyroidism resolved in 85% (47/55) of the patients.
Hypothyroidism occurred in 15% (128/851) of patients receiving LOQTORZI, including Grade 2 (8%). Sixty three percent of the 128 patients required thyroid hormone replacement therapy. LOQTORZI was withheld in 0.5% of patients. Of the 4 patients in whom LOQTORZI was withheld, 3 patients reinitiated LOQTORZI.
Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold or permanently discontinue LOQTORZI depending on severity
Diabetes mellitus occurred in 0.9% (8/851) of patients receiving LOQTORZI, including Grade 4 (0.1%), Grade 3 (0.7%), and Grade 2 (0.1%). Diabetes mellitus led to permanent discontinuation in 0.4% of patients. Six of the 8 (75%) patients with diabetes mellitus required long-term insulin therapy.
LOQTORZI in combination with cisplatin and gemcitabine can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.7% (1/146) of patients receiving LOQTORZI. The one patient with immune-mediated nephritis (Grade 4) required systemic corticosteroids and nephritis led to discontinuation of LOQTORZI. Nephritis resolved in this patient.
LOQTORZI can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.5% (4/851) of patients receiving LOQTORZI, including Grade 3 (0.5%) adverse reactions. Nephritis resolved in 75% (3/4) of these patients.
LOQTORZI can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Withhold or permanently discontinue LOQTORZI depending on severity
Immune-mediated dermatologic adverse reactions occurred in 8% (12/146) of patients receiving LOQTORZI, including Grade 3 (3.4%) and Grade 2 (1.4%) adverse reactions. Systemic corticosteroids were required in 25% (3/12) of the patients with immune-mediated dermatologic adverse reactions. Immune-mediated dermatologic adverse reactions led to permanent discontinuation of LOQTORZI in 2.1% (3) of patients. Immune-mediated dermatologic adverse reactions resolved in 92% (11/12) of these patients.
Immune-mediated dermatologic adverse reactions occurred in 4% (34/851) of patients receiving LOQTORZI, including Grade 3 (0.4%) and Grade 2 (1.4%) adverse reactions. Immune-mediated dermatologic adverse reactions led to withholding of LOQTORZI in 0.4% (3) of the patients. Systemic corticosteroids were required in 12% (4/34) of the patients with immune-mediated dermatologic adverse reactions. Immune-mediated dermatologic adverse reactions resolved in 71% (24/34) of these patients.
The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received LOQTORZI or were reported with the use of other PD1/PD-L1 blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions.
Dosage and Administration (
In combination with cisplatin and gemcitabine:
- 240 mg intravenously every three weeks
As a single agent:
- 3 mg/kg intravenously every two weeks
The recommended dosages of LOQTORZI are provided in Table 1. Administer as recommended
| Indication | Recommended Dosage of LOQTORZI | Duration of Treatment |
|---|---|---|
| First-line NPC | 240 mg every three weeks | Until disease progression, unacceptable toxicity, or up to 24 months. |
| Recurrent NPC | 3 mg/kg every two weeks | Until disease progression or unacceptable toxicity. |
No dose reductions of LOQTORZI are recommended. In general, withhold LOQTORZI for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue LOQTORZI for life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce prednisone to 10 mg per day or less (or equivalent) within 12 weeks of initiating steroids.
Dosage modifications for LOQTORZI for adverse reactions that require management different from these general guidelines are summarized in Table 2.
| Adverse Reaction | SeverityBased on National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) version 5.0 | Dose Modification |
|---|---|---|
| ALT=alanine aminotransferase, AST=aspartate aminotransferase, DRESS=drug rash with eosinophilia and systemic symptoms, SJS=Stevens Johnson syndrome, TEN=toxic epidermal necrolysis, ULN=upper limit of normal | ||
Immune-Related Adverse Reactions [see Warnings and Precautions (5.1)] | ||
| Pneumonitis | Grade 2 | WithholdResume LOQTORZI in patients with complete or partial resolution to Grade 0-1 after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to 10 mg per day or less (or equivalent) within 12 weeks of initiating steroids. |
| Grades 3 or 4 | Permanently discontinue | |
| Colitis | Grade 2 or 3 | Withhold |
| Grade 4 | Permanently discontinue | |
| Hepatitis with no tumor involvement of the liver | AST/ALT increases to more than 3 and up to 8 times ULN or Total bilirubin increases to more than 1.5 and up to 3 times ULN | Withhold |
| AST or ALT increases to more than 8 times ULN or Total bilirubin increases to more than 3 times ULN | Permanently discontinue | |
| Hepatitis with tumor involvement of the liverIf AST and ALT are less than or equal to ULN at baseline in patients with liver involvement, withhold or permanently discontinue LOQTORZI based on recommendations for hepatitis with no liver involvement. | Baseline AST or ALT is more than 1 and up to 3 times ULN and increases to more than 5 and up to 10 times ULN or Baseline AST or ALT is more than 3 and up to 5 times ULN and increases to more than 8 and up to 10 times ULN | Withhold |
| Baseline AST or ALT is above the ULN and increases to more than 10 times ULN or Total bilirubin increases to more than 3 times ULN | Permanently discontinue | |
| Endocrinopathies | Grades 3 or 4 | Withhold until clinically stable or permanently discontinue depending on severity |
| Nephritis with Renal Dysfunction | Grade 2 or 3 increased blood creatinine | Withhold |
| Grade 4 increased blood creatinine | Permanently discontinue | |
| Exfoliative Dermatologic Conditions | Suspected SJS, TEN, or DRESS | Withhold |
| Confirmed SJS, TEN, or DRESS | Permanently discontinue | |
| Myocarditis | Grades 2, 3, or 4 | Permanently discontinue |
| Neurological toxicities | Grade 2 | Withhold |
| Grade 3-4 | Permanently discontinue | |
Other Adverse Reactions | ||
| Infusion-related reactions [see Warnings and Precautions (5.2)] | Grade 1 or 2 | Interrupt or slow the rate of infusion |
| Grade 3 or 4 | Stop infusion Permanently discontinue | |
- Visually inspect the solution for particulate matter and discoloration. The solution is clear to slightly opalescent, colorless to slightly yellow. Discard the vial if visible particles are observed.
- Withdraw the required volume of LOQTORZI and inject slowly into a 100 mL or 250 mL infusion bag containing 0.9% Sodium Chloride Injection, USP.Mix diluted solution by gentle inversion.Do not shake. The final concentration of the diluted solution should be between 1 mg/mL to 3 mg/mL.
- Discard any unused portion left in the vial.
LOQTORZI does not contain a preservative.
If the diluted solution is not administered immediately, store either:
- At room temperature, 20°C to 25°C (68°F to 77°F), for no more than 8 hours from the time of dilution to the completion of the infusion. Discard diluted solution stored at room temperature after 8 hours.
Or - Refrigerated at 2°C to 8°C (36°F to 46°F) for no more than 24 hours from the time of dilution to the completion of the infusion. If refrigerated, allow the diluted solution to come to room temperature prior to administration. Discard the refrigerated diluted solution after 24 hours.
Do not freeze.
- Administer diluted solution intravenously via an infusion pump using an in-line aseptic filter (0.2 or 0.22 micron).
- First Infusion: Infuse over at least 60 minutes.
- Subsequent infusions: If no infusion-related reactions occurred during the first infusion, subsequent infusions may be administered over 30 minutes[see Dose Modifications (2.2)].
- Do not co-administer other drugs through the same intravenous line.
- When administered on the same day as chemotherapy, LOQTORZI should be administered prior to chemotherapy.
- Refer to the Prescribing Information for cisplatin and gemcitabine for recommended dosing information.
LOQTORZI is a programmed death receptor-1 (PD-1)- blocking antibody indicated:
- in combination with cisplatin and gemcitabine, for first-line treatment of adults with metastatic or with recurrent locally advanced nasopharyngeal carcinoma (NPC) ()
1.1 First-line Treatment of Metastatic or Recurrent, Locally Advanced NPC with Cisplatin and GemcitabineLOQTORZI is indicated, in combination with cisplatin and gemcitabine, for the first-line treatment of adults with metastatic or with recurrent, locally advanced nasopharyngeal carcinoma (NPC).
- as a single agent for the treatment of adults with recurrent unresectable or metastatic NPC with disease progression on or after a platinum-containing chemotherapy ()
1.2 Previously Treated Unresectable or Metastatic NPCLOQTORZI is indicated, as a single agent, for the treatment of adults with recurrent unresectable or metastatic NPC with disease progression on or after a platinum-containing chemotherapy.
In combination with cisplatin and gemcitabine:
- 240 mg intravenously every three weeks ()
2.1 Recommended DosageThe recommended dosages of LOQTORZI are provided in Table 1. Administer as recommended
[see Dosage and Administration (2.3)].Table 1: Recommended Dosage Indication Recommended Dosage of LOQTORZI Duration of Treatment First-line NPC 240 mg every three weeks Until disease progression, unacceptable toxicity, or up to 24 months. Recurrent NPC 3 mg/kg every two weeks Until disease progression or unacceptable toxicity.
As a single agent:
- 3 mg/kg intravenously every two weeks ()
2.1 Recommended DosageThe recommended dosages of LOQTORZI are provided in Table 1. Administer as recommended
[see Dosage and Administration (2.3)].Table 1: Recommended Dosage Indication Recommended Dosage of LOQTORZI Duration of Treatment First-line NPC 240 mg every three weeks Until disease progression, unacceptable toxicity, or up to 24 months. Recurrent NPC 3 mg/kg every two weeks Until disease progression or unacceptable toxicity.
Injection: 240 mg/6 mL (40 mg/mL) clear to slightly opalescent, colorless to slightly yellow solution in a single-dose vial.
There are no data on the presence of toripalimab-tpzi in human milk or its effects on the breastfed child or on milk production. Maternal IgG is known to be present in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to toripalimab-tpzi are unknown. Because of the potential for serious adverse reactions in breastfed children, advise lactating women not to breastfeed during treatment with LOQTORZI and for 4 months after the last dose.
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