Jemperli

JEMPERLI is a programmed death receptor-1 (PD-1)–blocking antibody indicated:

• •in combination with carboplatin and paclitaxel, followed by JEMPERLI as a single agent, for the treatment of adult patients with primary advanced or recurrent endometrial cancer (EC). (
  1.1 Endometrial Cancer

  JEMPERLI, in combination with carboplatin and paclitaxel, followed by JEMPERLI as a single agent, is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer (EC).

  JEMPERLI, as a single agent, is indicated for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced EC, as determined by an FDA-approved test, that has progressed on or following prior treatment with a platinum-containing regimen in any setting and are not candidates for curative surgery or radiation

  [see Dosage and Administration ].
  )
• •as a single agent for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced EC, as determined by an FDA-approved test, that has progressed on or following prior treatment with a platinum-containing regimen in any setting and are not candidates for curative surgery or radiation. (
  1.1 Endometrial Cancer

  JEMPERLI, in combination with carboplatin and paclitaxel, followed by JEMPERLI as a single agent, is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer (EC).

  JEMPERLI, as a single agent, is indicated for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced EC, as determined by an FDA-approved test, that has progressed on or following prior treatment with a platinum-containing regimen in any setting and are not candidates for curative surgery or radiation

  [see Dosage and Administration ].
  ,
  2.1 Patient Selection

  Single Agent

  Select patients for treatment with JEMPERLI as a single agent based on the presence of dMMR in tumor specimens in:

  • •recurrent or advanced EC
    [see Clinical Studies ]
    .
  • •recurrent or advanced solid tumors
    [see Clinical Studies ]
    .

  Information on FDA-approved tests for the detection of dMMR status is available at https://www.fda.gov/companiondiagnostics.

  Because the effect of prior chemotherapy on test results for dMMR in patients with high-grade gliomas is unclear, it is recommended to test for this marker in the primary tumor specimen obtained prior to initiation of temozolomide chemotherapy in patients with high-grade gliomas.
  )

• •as a single agent for the treatment of adult patients with dMMR recurrent or advanced solid tumors, as determined by an FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options.¹ (
  1.2 Mismatch Repair Deficient Recurrent or Advanced Solid Tumors

  JEMPERLI, as a single agent, is indicated for the treatment of adult patients with dMMR recurrent or advanced solid tumors, as determined by an FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options

  [see Dosage and Administration ].

  This indication is approved under accelerated approval based on tumor response rate and durability of response

  [see Clinical Studies ].

  Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
  ,
  2.1 Patient Selection

  Single Agent

  Select patients for treatment with JEMPERLI as a single agent based on the presence of dMMR in tumor specimens in:

  • •recurrent or advanced EC
    [see Clinical Studies ]
    .
  • •recurrent or advanced solid tumors
    [see Clinical Studies ]
    .

  Information on FDA-approved tests for the detection of dMMR status is available at https://www.fda.gov/companiondiagnostics.

  Because the effect of prior chemotherapy on test results for dMMR in patients with high-grade gliomas is unclear, it is recommended to test for this marker in the primary tumor specimen obtained prior to initiation of temozolomide chemotherapy in patients with high-grade gliomas.
  )

¹This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). (

• •JEMPERLI, in combination with carboplatin and paclitaxel, for primary advanced or recurrent EC: 500 mg every 3 weeks for 6 cycles followed by 1,000 mg monotherapy every 6 weeks for all cycles thereafter. (
  2.2 Recommended Dosage

  The recommended dosage for JEMPERLI is presented in Table 1.

  Table 1. Recommended Dosage of JEMPERLI

  dMMR = Mismatch Repair Deficient; EC = endometrial cancer.
  a30-minute intravenous infusion.
  bRefer to the Prescribing Information for the agents administered in combination with JEMPERLI, as appropriate.
  Indication	Recommended Dosage	Duration/Timing of Treatment
  Combination Therapy
  Adults with primary advanced or recurrent EC	500 mgaJEMPERLI every 3 weeks for 6  cycles in combination with carboplatin and paclitaxelbfollowed by 1,000 mg JEMPERLI as monotherapy every 6 weeks for all cycles thereafter. Administer JEMPERLI prior to carboplatin and paclitaxel when given on the same day.	Until disease progression, unacceptable toxicity, or up to 3 years.
  Monotherapy
  Adults with dMMR recurrent or advanced EC and dMMR recurrent or advanced solid tumors	500 mgaJEMPERLI every 3 weeks for 4 cycles followed by 1,000 mgaJEMPERLI every 6 weeks for all cycles thereafter.	Until disease progression or unacceptable toxicity.
  )
• •JEMPERLI, as a single agent, for dMMR recurrent or advanced EC: 500 mg every 3 weeks for 4 cycles followed by 1,000 mg every 6 weeks for all cycles thereafter. (
  2.2 Recommended Dosage

  The recommended dosage for JEMPERLI is presented in Table 1.

  Table 1. Recommended Dosage of JEMPERLI

  dMMR = Mismatch Repair Deficient; EC = endometrial cancer.
  a30-minute intravenous infusion.
  bRefer to the Prescribing Information for the agents administered in combination with JEMPERLI, as appropriate.
  Indication	Recommended Dosage	Duration/Timing of Treatment
  Combination Therapy
  Adults with primary advanced or recurrent EC	500 mgaJEMPERLI every 3 weeks for 6  cycles in combination with carboplatin and paclitaxelbfollowed by 1,000 mg JEMPERLI as monotherapy every 6 weeks for all cycles thereafter. Administer JEMPERLI prior to carboplatin and paclitaxel when given on the same day.	Until disease progression, unacceptable toxicity, or up to 3 years.
  Monotherapy
  Adults with dMMR recurrent or advanced EC and dMMR recurrent or advanced solid tumors	500 mgaJEMPERLI every 3 weeks for 4 cycles followed by 1,000 mgaJEMPERLI every 6 weeks for all cycles thereafter.	Until disease progression or unacceptable toxicity.
  )
• •JEMPERLI, as a single agent, for dMMR recurrent or advanced solid tumors: 500 mg every 3 weeks for 4 cycles followed by 1,000 mg every 6 weeks for all cycles thereafter. (
  2.2 Recommended Dosage

  The recommended dosage for JEMPERLI is presented in Table 1.

  Table 1. Recommended Dosage of JEMPERLI

  dMMR = Mismatch Repair Deficient; EC = endometrial cancer.
  a30-minute intravenous infusion.
  bRefer to the Prescribing Information for the agents administered in combination with JEMPERLI, as appropriate.
  Indication	Recommended Dosage	Duration/Timing of Treatment
  Combination Therapy
  Adults with primary advanced or recurrent EC	500 mgaJEMPERLI every 3 weeks for 6  cycles in combination with carboplatin and paclitaxelbfollowed by 1,000 mg JEMPERLI as monotherapy every 6 weeks for all cycles thereafter. Administer JEMPERLI prior to carboplatin and paclitaxel when given on the same day.	Until disease progression, unacceptable toxicity, or up to 3 years.
  Monotherapy
  Adults with dMMR recurrent or advanced EC and dMMR recurrent or advanced solid tumors	500 mgaJEMPERLI every 3 weeks for 4 cycles followed by 1,000 mgaJEMPERLI every 6 weeks for all cycles thereafter.	Until disease progression or unacceptable toxicity.
  )
• •Administer as an intravenous infusion over 30 minutes. (
  2.2 Recommended Dosage

  The recommended dosage for JEMPERLI is presented in Table 1.

  Table 1. Recommended Dosage of JEMPERLI

  dMMR = Mismatch Repair Deficient; EC = endometrial cancer.
  a30-minute intravenous infusion.
  bRefer to the Prescribing Information for the agents administered in combination with JEMPERLI, as appropriate.
  Indication	Recommended Dosage	Duration/Timing of Treatment
  Combination Therapy
  Adults with primary advanced or recurrent EC	500 mgaJEMPERLI every 3 weeks for 6  cycles in combination with carboplatin and paclitaxelbfollowed by 1,000 mg JEMPERLI as monotherapy every 6 weeks for all cycles thereafter. Administer JEMPERLI prior to carboplatin and paclitaxel when given on the same day.	Until disease progression, unacceptable toxicity, or up to 3 years.
  Monotherapy
  Adults with dMMR recurrent or advanced EC and dMMR recurrent or advanced solid tumors	500 mgaJEMPERLI every 3 weeks for 4 cycles followed by 1,000 mgaJEMPERLI every 6 weeks for all cycles thereafter.	Until disease progression or unacceptable toxicity.
  )
• •For complete dosing instructions, see full prescribing information.

Injection: 500 mg/10 mL (50 mg/mL) clear to slightly opalescent, colorless to yellow solution in a single-dose vial for intravenous infusion after dilution.

Lactation: Advise not to breastfeed. (

• •Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune‑mediated pneumonitis, immune-mediated colitis, immune‑mediated hepatitis, immune-mediated endocrinopathies, immune-mediated nephritis with renal dysfunction, immune‑mediated dermatologic adverse reactions, and solid organ transplant rejection. Monitor for signs and symptoms of immune‑mediated adverse reactions. Evaluate clinical chemistries, including liver enzymes, creatinine, and thyroid function, at baseline and periodically during treatment. Withhold or permanently discontinue JEMPERLI and administer corticosteroids based on the severity of reaction. (
  2.3 Dosage Modifications for Adverse Reactions

  No dose reductions of JEMPERLI are recommended. In general, withhold JEMPERLI for severe (Grade 3) immune‑mediated adverse reactions. Permanently discontinue JEMPERLI 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 corticosteroid dose to 10 mg or less of prednisone equivalent per day within 12 weeks of initiating steroids.

  Dosage modifications for JEMPERLI for adverse reactions that require management different from these general guidelines are summarized in Table 2.

  Table 2. Recommended Dosage Modifications for Adverse Reactions

  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. aBased on National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0. bResume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids. cIf AST and ALT are less than or equal to ULN at baseline in patients with liver involvement, withhold or permanently discontinue JEMPERLI based on recommendations for hepatitis with no liver involvement.
  Adverse Reaction	Severitya	Dosage Modification
  Immune-Mediated Adverse Reactions [see Warnings and Precautions ]
  Pneumonitis	Grade 2	Withholdb
  	Grade 3 or 4 or recurrent Grade 2	Permanently discontinue
  Colitis	Grade 2 or 3	Withholdb
  	Grade 4	Permanently discontinue
  Hepatitis with no tumor involvement of the liver	AST or 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	Withholdb
  	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 liverc	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	Withholdb
  	AST or ALT increases to more than 10 times ULN or Total bilirubin increases to more than 3 times ULN	Permanently discontinue
  Endocrinopathies	Grade 2, 3, or 4	Withhold until clinically stable or permanently discontinue, depending on severityb
  Nephritis with renal dysfunction	Grade 2 or 3 increased blood creatinine	Withholdb
  	Grade 4 increased blood creatinine	Permanently discontinue
  Exfoliative dermatologic conditions	Suspected SJS, TEN, or DRESS	Withholdb
  	Confirmed SJS, TEN, or DRESS	Permanently discontinue
  Myocarditis	Grade 2, 3, or 4	Permanently discontinue
  Neurological toxicities	Grade 2	Withholdb
  	Grade 3 or 4	Permanently discontinue
  Other Adverse Reactions
  Infusion-related reactions [see Warnings and Precautions ]	Grade 1 or 2	Interrupt or slow the rate of infusion
  	Grade 3 or 4	Permanently discontinue
  ,
  5.1 Severe and Fatal Immune-Mediated Adverse Reactions

  JEMPERLI 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 in WARNINGS AND PRECAUTIONS may not include all possible severe and fatal immune‑mediated reactions.

  Immune-mediated adverse reactions, which can be severe or fatal, can occur in any organ system or tissue. Immune‑mediated adverse reactions can occur at any time after starting a PD-1/PD-L1–blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1–blocking antibodies, they 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 tests 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 JEMPERLI depending on severity

  [see Dosage and Administration ]

  . In general, if JEMPERLI requires interruption or discontinuation, administer systemic corticosteroids (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 reaction is not controlled with corticosteroids.

  Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies, dermatologic reactions) are discussed below.

  Immune-Mediated Pneumonitis

  JEMPERLI can cause immune-mediated pneumonitis, which can be fatal. 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 2.3% (14/605) of patients receiving JEMPERLI, including Grade 2 (1.3%), Grade 3 (0.8%) and Grade 4 (0.2%) pneumonitis. Pneumonitis led to discontinuation of JEMPERLI in 1.3% of patients.

  Systemic corticosteroids were required in 79% (11/14) of patients with pneumonitis. Pneumonitis resolved in 11 of the 14 patients. JEMPERLI was withheld for 9 patients. Five patients reinitiated JEMPERLI after symptom improvement; of these, 2 patients had recurrence of pneumonitis.

  Immune-Mediated Colitis

  JEMPERLI can cause immune-mediated colitis. Cytomegalovirus infection/reactivation have occurred in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1–blocking antibodies. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.

  Immune-mediated colitis occurred in 1.3% (8/605) of patients receiving JEMPERLI, including Grade 2 (0.7%) and Grade 3 (0.7%) adverse reactions. Colitis led to discontinuation of JEMPERLI in 1 (0.2%) patient.

  Systemic corticosteroids were required in 75% (6/8) of patients with colitis. Colitis resolved in 5 of the 8 patients. Of the 4 patients in whom JEMPERLI was withheld for colitis, all reinitiated treatment with JEMPERLI; of these, 1 patient had recurrence of colitis.

  Immune-Mediated Hepatitis

  JEMPERLI can cause immune-mediated hepatitis, which can be fatal.

  Immune-mediated hepatitis occurred in 0.5% (3/605) of patients receiving JEMPERLI, all were Grade 3. Hepatitis led to discontinuation of JEMPERLI in 1 (0.2%) patient. Systemic corticosteroids were required in 2 patients with hepatitis and the events resolved in 2 of the 3 patients.

  Immune-Mediated Endocrinopathies

  Adrenal Insufficiency:

  JEMPERLI can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment per institutional guidelines, including hormone replacement as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity

  [see Dosage and Administration ]

  .

  Adrenal insufficiency occurred in 1.2% (7/605) patients receiving JEMPERLI, including Grade 2 (0.5%) and Grade 3 (0.7%). Adrenal insufficiency resulted in discontinuation in 1 (0.2%) patient and resolved in 4 of the 7 patients. Of the 4 patients in whom JEMPERLI was withheld for adrenal insufficiency, all reinitiated treatment with JEMPERLI. Systemic corticosteroids were required in 5 of the 7 patients with adrenal insufficiency.

  Hypophysitis:

  JEMPERLI can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity

  [see Dosage and Administration ]

  .

  JEMPERLI in Combination with Carboplatin and Paclitaxel:

  Hypophysitis (Grade 3) occurred in 0.4% (1/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Systemic corticosteroids were required, and the event resolved. JEMPERLI was withheld and the patient reinitiated treatment.

  JEMPERLI as a Single Agent:

  Hypophysitis (Grade 2) occurred in 0.2% (1/605) of patients receiving JEMPERLI as a single agent. Systemic corticosteroids were required, and the event did not resolve. JEMPERLI was withheld and the patient reinitiated treatment.

  Thyroid Disorders:

  JEMPERLI can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate thyroid hormone replacement or medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity

  [see Dosage and Administration ]

  .

  Thyroiditis:

  Thyroiditis occurred in 0.5% (3/605) of patients receiving JEMPERLI; all were Grade 2. Systemic corticosteroids were required in 1 of 3 patients and anti-thyroid therapy was required for 2 of 3 patients with thyroiditis. JEMPERLI was withheld for 1 patient and the patient reinitiated treatment. None of the events of thyroiditis resolved; there were no discontinuations of JEMPERLI due to thyroiditis.

  Hypothyroidism: JEMPERLI in Combination with Carboplatin and Paclitaxel:

  Hypothyroidism occurred in 12% (30/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel, all of which were Grade 2. Hypothyroidism led to discontinuation of JEMPERLI in 1 patient and resolved in 23% (7/30) of patients. JEMPERLI was withheld for 5 patients and all reinitiated treatment with JEMPERLI. Thyroid hormone replacement was required for 27 of the 30 patients with hypothyroidism.

  JEMPERLI as a Single Agent:

  Hypothyroidism occurred in 8% (46/605) of patients receiving JEMPERLI as a single agent, all of which were Grade 2. Hypothyroidism did not lead to discontinuation of JEMPERLI and resolved in 37% (17/46) of patients. JEMPERLI was withheld for 2 patients and both reinitiated treatment. Thyroid hormone replacement therapy was required for 45 of the 46 patients with hypothyroidism.

  Hyperthyroidism: JEMPERLI in Combination with Carboplatin and Paclitaxel:

  Hyperthyroidism occurred in 3.3% (8/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel, including Grade 2 (2.9%) and Grade 3 (0.4%). Hyperthyroidism did not lead to discontinuation of JEMPERLI and resolved in 75% (6/8) of patients

  .

  JEMPERLI was withheld for 1 patient and the patient reinitiated treatment. Anti-thyroid therapy was required for 2 of the 8 patients while systemic corticosteroids were required for 1 of the 8 patients with hyperthyroidism.

  JEMPERLI as a Single Agent:

  Hyperthyroidism occurred in 2.3% (14/605) of patients receiving JEMPERLI as a single agent, including Grade 2 (2.1%) and Grade 3 (0.2%). Hyperthyroidism did not lead to discontinuation of JEMPERLI and resolved in 71% (10/14) of the 14 patients. JEMPERLI was withheld for 2 patients and both reinitiated treatment. Anti-thyroid therapy was required for 10 of the 14 patients with hyperthyroidism.

  Type 1 Diabetes Mellitus, Which Can Present with Diabetic Ketoacidosis:

  JEMPERLI can cause 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 JEMPERLI depending on severity

  [see Dosage and Administration ]

  .

  JEMPERLI in Combination with Carboplatin and Paclitaxel:

  Type 1 diabetes mellitus (Grade 3) occurred in 0.4% (1/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Type 1 diabetes mellitus led to withholding JEMPERLI; the patient reinitiated treatment and required long-term insulin therapy.

  JEMPERLI as a Single Agent:

  Type 1 diabetes mellitus occurred in 0.2% (1/605) of patients receiving JEMPERLI as a single agent, which was Grade 3. Type 1 diabetes mellitus did not result in treatment discontinuation and did not resolve.

  Immune-Mediated Nephritis with Renal Dysfunction

  JEMPERLI can cause immune-mediated nephritis, which can be fatal. Nephritis, including tubulointerstitial nephritis, occurred in 0.5% (3/605) of patients receiving JEMPERLI; all were Grade 2. Nephritis led to discontinuation of JEMPERLI in 1 (0.2%) patient and resolved in all patients. JEMPERLI was withheld for 1 patient and the patient reinitiated treatment. Systemic corticosteroids were required in 2 of the 3 patients experiencing nephritis.

  Immune-Mediated Dermatologic Adverse Reactions

  JEMPERLI can cause immune-mediated rash or dermatitis. Bullous and exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), have occurred with PD‑1/PD‑L1–blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/exfoliative rashes. Withhold or permanently discontinue JEMPERLI depending on severity

  [see Dosage and Administration ]

  .

  Other Immune-Mediated Adverse Reactions

  The following clinically significant immune-mediated adverse reactions occurred in <1% of the 605 patients treated with JEMPERLI or were reported with the use of other PD-1/PD-L1–blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions.

  Nervous System:

  Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis, Guillain‑Barré syndrome, nerve paresis, autoimmune neuropathy.

  Cardiac/Vascular:

  Myocarditis, pericarditis, vasculitis.

  Ocular:

  Uveitis, iritis, other ocular inflammatory toxicities. Some cases can be associated with retinal detachment. Various grades of visual impairment to include 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, including 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.

  Endocrine:

  Hypoparathyroidism.

  Other (Hematologic/Immune):

  Autoimmune hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection, other transplant (including corneal graft) rejection.
  )
• •Infusion-related reactions: Interrupt, slow the rate of infusion, or permanently discontinue JEMPERLI based on severity of reaction. (
  2.3 Dosage Modifications for Adverse Reactions

  No dose reductions of JEMPERLI are recommended. In general, withhold JEMPERLI for severe (Grade 3) immune‑mediated adverse reactions. Permanently discontinue JEMPERLI 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 corticosteroid dose to 10 mg or less of prednisone equivalent per day within 12 weeks of initiating steroids.

  Dosage modifications for JEMPERLI for adverse reactions that require management different from these general guidelines are summarized in Table 2.

  Table 2. Recommended Dosage Modifications for Adverse Reactions

  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. aBased on National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0. bResume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids. cIf AST and ALT are less than or equal to ULN at baseline in patients with liver involvement, withhold or permanently discontinue JEMPERLI based on recommendations for hepatitis with no liver involvement.
  Adverse Reaction	Severitya	Dosage Modification
  Immune-Mediated Adverse Reactions [see Warnings and Precautions ]
  Pneumonitis	Grade 2	Withholdb
  	Grade 3 or 4 or recurrent Grade 2	Permanently discontinue
  Colitis	Grade 2 or 3	Withholdb
  	Grade 4	Permanently discontinue
  Hepatitis with no tumor involvement of the liver	AST or 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	Withholdb
  	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 liverc	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	Withholdb
  	AST or ALT increases to more than 10 times ULN or Total bilirubin increases to more than 3 times ULN	Permanently discontinue
  Endocrinopathies	Grade 2, 3, or 4	Withhold until clinically stable or permanently discontinue, depending on severityb
  Nephritis with renal dysfunction	Grade 2 or 3 increased blood creatinine	Withholdb
  	Grade 4 increased blood creatinine	Permanently discontinue
  Exfoliative dermatologic conditions	Suspected SJS, TEN, or DRESS	Withholdb
  	Confirmed SJS, TEN, or DRESS	Permanently discontinue
  Myocarditis	Grade 2, 3, or 4	Permanently discontinue
  Neurological toxicities	Grade 2	Withholdb
  	Grade 3 or 4	Permanently discontinue
  Other Adverse Reactions
  Infusion-related reactions [see Warnings and Precautions ]	Grade 1 or 2	Interrupt or slow the rate of infusion
  	Grade 3 or 4	Permanently discontinue
  ,
  5.2 Infusion-Related Reactions

  Severe or life-threatening infusion-related reactions have been reported with PD-1/PD-L1–blocking antibodies. Severe infusion-related reactions (Grade 3) occurred in 0.2% (1/605) of patients receiving JEMPERLI. All patients recovered from the infusion-related reactions.

  Monitor patients for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion or permanently discontinue JEMPERLI based on severity of reaction

  [see Dosage and Administration ]

  .
  )
• •Complications of allogeneic hematopoietic stem cell transplantation (HSCT): Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with a PD‑1/PD-L1–blocking antibody. (
  5.3 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 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: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. (
  5.4 Embryo-Fetal Toxicity

  Based on its mechanism of action, JEMPERLI 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 pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with JEMPERLI and for 4 months after the last dose

  [see Use in Specific Populations ]

  .
  ,
  8.1 Pregnancy

  Risk Summary

  Based on its mechanism of action, JEMPERLI can cause fetal harm when administered to a pregnant woman

  [see Clinical Pharmacology ]

  . There are no available data on the use of JEMPERLI 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 resulting in fetal death

  (see )

  . Human IgG4 immunoglobulins (IgG4) are known to cross the placental barrier; therefore, dostarlimab-gxly has the potential to 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 JEMPERLI 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 JEMPERLI during pregnancy 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 dostarlimab-gxly may increase the risk of developing immune-mediated disorders or altering the normal immune response.
  ,
  8.3 Females and Males of Reproductive Potential

  JEMPERLI can cause fetal harm when administered to a pregnant woman

  [see Use in Specific Populations ]

  .

  Pregnancy Testing

  Verify pregnancy status in females of reproductive potential prior to initiating JEMPERLI

  [see Use in Specific Populations ]

  .

  Contraception

  Females:

  Advise females of reproductive potential to use effective contraception during treatment with JEMPERLI and for 4 months after the last dose.
  )