Loqtorzi
(toripalimab-tpzi)Dosage & Administration
In combination with cisplatin and gemcitabine:
As a single agent:
First Infusion: Infuse over 60 minutes.
Subsequent Infusions: If no infusion-related reactions occurred during the first infusion, subsequent infusions may be administered over 30 minutes.
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Loqtorzi Prescribing Information
First-line Treatment of Metastatic or Recurrent, Locally Advanced NPC with Cisplatin and Gemcitabine
LOQTORZI 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).
Previously Treated Unresectable or Metastatic NPC
LOQTORZI 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.
Recommended Dosage
The recommended dosages of LOQTORZI are provided in Table 1. Administer as recommended [see Dosage and Administration (2.3)].
| 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. |
Dosage Modifications
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 | Severity * | 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 | Withhold † |
| 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 liver ‡ | 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 | |
Preparation and Administration
Preparation for Intravenous Infusion
- 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.
Storage of Diluted Solution for Infusion
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.
Administration
- 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.
Injection: 240 mg/6 mL (40 mg/mL) clear to slightly opalescent, colorless to slightly yellow solution in a single-dose vial.
Pregnancy
Risk Summary
Based on its mechanism of action, LOQTORZI can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. There are no available data on the use of LOQTORZI in pregnant women. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus and result in fetal death (see Data). Human IgG4 immunoglobulins (IgG4) are known to cross the placenta; therefore, LOQTORZI can potentially be transmitted from the mother to the developing fetus. Advise women of the potential risk to a fetus.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data
Animal Data
Animal reproduction studies have not been conducted with LOQTORZI to evaluate its effect on reproduction and fetal development. A central function of the PD-1/PD-L1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to the fetus. In murine models of pregnancy, blockade of PD-L1 signaling has been shown to disrupt tolerance to the fetus and to result in an increase in fetal loss; therefore, potential risks of administering LOQTORZI during pregnancy could include increased rates of abortion or stillbirth. As reported in the literature, there were no malformations related to the blockade of PD-1/PD-L1 signaling in the offspring of these animals; however, immune-mediated disorders occurred in PD-1 and PD-L1 knockout mice. Based on its mechanism of action, fetal exposure to toripalimab-tpzi may increase the risk of developing immune-mediated disorders or altering the normal immune response.
Lactation
Risk Summary
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.
Females and Males of Reproductive Potential
LOQTORZI can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].
Pregnancy Testing
Verify the pregnancy status of females of reproductive potential prior to initiating LOQTORZI [see Use in Specific Populations (8.1)].
Contraception
Females
Advise females of reproductive potential to use effective contraception during treatment with LOQTORZI and for 4 months after the last dose.
Pediatric Use
The safety and effectiveness of LOQTORZI have not been established in pediatric patients [see Indications and Usage (1)].
Geriatric Use
Of the 146 patients with NPC who were treated with LOQTORZI in combination with cisplatin and gemcitabine 7 (4.8%) were 65 years or older; there were no patients 75 years and older. Clinical studies of LOQTORZI in combination with cisplatin and gemcitabine did not include a sufficient number of patients aged 65 years and over with NPC to determine whether they respond differently from younger patients.
Of the 851 patients with tumor types including nasopharyngeal carcinoma or other types of tumors from the safety pool treated with LOQTORZI as a single agent, 171 (20%) patients were 65 years or older and 13 (1.5%) patients were 75 years and older. No overall differences in safety were observed between elderly patients and younger patients [see Adverse Reactions (6.1)].
Of the 190 patients with NPC treated with LOQTORZI as single agent, 10 (5%) patients were 65 years or older; there were no patients 75 years and older. Clinical studies of LOQTORZI did not include sufficient numbers of patients aged 65 years and over with NPC to determine whether they respond differently from younger patients.
None.
Severe and Fatal Immune-Mediated Adverse Reactions
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 [see Dosage and Administration (2.2)]. In general, if LOQTORZI requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.
Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.
Immune-Mediated Pneumonitis
LOQTORZI in Combination with Cisplatin and Gemcitabine
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 as a Single-Agent
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.
Immune-Mediated Colitis
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.
LOQTORZI as a Single-Agent
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.
Hepatotoxicity and Immune-Mediated Hepatitis
LOQTORZI in Combination with Cisplatin and Gemcitabine
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 as a Single-Agent
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.
Immune-Mediated Endocrinopathies
Adrenal Insufficiency
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 [see Dosage and Administration (2.2)].
LOQTORZI as a Single-Agent
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. Systemic corticosteroids were required in 75% (3/4) of the patients with adrenal insufficiency. Adrenal insufficiency led to withholding of LOQTORZI in 0.1% (1/851) of patients. In the one patient in whom LOQTORZI was withheld, LOQTORZI was reinitiated after symptom improvement.
Hypophysitis
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 [see Dosage and Administration (2.2)].
LOQTORZI as a Single-Agent
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.
Thyroid Disorders
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 [see Dosage and Administration (2.2)].
LOQTORZI in Combination with Cisplatin and Gemcitabine
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.
LOQTORZI as a Single-Agent
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.
Type 1 Diabetes Mellitus, which can present with Diabetic Ketoacidosis
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 [see Dosage and Administration (2.2)].
LOQTORZI as a Single-Agent
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.
Immune-Mediated Nephritis with Renal Dysfunction
LOQTORZI in Combination with Cisplatin and Gemcitabine
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 as a Single-Agent
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.
Immune-Mediated Dermatologic Adverse Reactions
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 [see Dosage and Administration (2.2)].
LOQTORZI in Combination with Cisplatin and Gemcitabine
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.
LOQTORZI as a Single-Agent
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.
Other Immune-Mediated Adverse Reactions
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.
Cardiac/Vascular: Myocarditis, pericarditis, vasculitis, pericardial effusion
Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy
Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.
Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis
Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis (and associated sequelae, including renal failure), arthritis, polymyalgia rheumatica, dermatomyositis
Endocrine: Hypoparathyroidism
Hematologic/Immune: 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.
Infusion-Related Reactions
LOQTORZI can cause severe or life-threatening infusion-related reactions including hypersensitivity and anaphylaxis.
LOQTORZI in Combination with Cisplatin and Gemcitabine
Infusion-related reactions have been reported in 4.1% of patients receiving LOQTORZI in combination with cisplatin and gemcitabine, including Grade 2 (0.7%) reactions.
LOQTORZI as a Single-Agent
Infusion-related reactions occurred in 2% of 851 patients receiving LOQTORZI as single agent, including Grade 3 (0.1%) and Grade 2 (0.6%). LOQTORZI was withheld for one Grade 3 infusion related reaction.
Monitor patients for signs and symptoms of infusion-related reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. Interrupt or slow the rate of infusion for mild (Grade 1) or moderate (Grade 2) infusion-related reactions. For severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions, stop infusion and permanently discontinue LOQTORZI [see Dosage and Administration (2.2)].
Complications of Allogeneic HSCT
Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated 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.
Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody prior to or after an allogeneic HSCT.
Embryo-Fetal Toxicity
Based on its mechanism of action, LOQTORZI can cause fetal harm when administered to a pregnant woman. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death. Advise women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with LOQTORZI and for 4 months after the last dose [see Use in Specific Populations (8.1, 8.3)].