ADVERSE REACTIONS SECTION.

6ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling:oSevere and fatal immune-mediated adverse reactions [see Warnings and Precautions (5.1)]oInfusion-related reactions [see Warnings and Precautions (5.2)]. oSevere and fatal immune-mediated adverse reactions [see Warnings and Precautions (5.1)]. oInfusion-related reactions [see Warnings and Precautions (5.2)]. Most common adverse reactions (>=20%) in patients with dMMR solid tumors are fatigue/asthenia, anemia, diarrhea, and nausea. Most common Grade or laboratory abnormalities (>=2%) are decreased lymphocytes, decreased sodium, increased alkaline phosphatase, and decreased albumin. (6.1)To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.The pooled safety population described in WARNINGS AND PRECAUTIONS reflects exposure to JEMPERLI as single-agent in 515 patients with advanced or recurrent solid tumors in the non-randomized, open-label, multicohort GARNET trial that enrolled 290 patients with endometrial cancer and 225 patients with other solid tumors. JEMPERLI was administered intravenously at doses of 500 mg every weeks for doses followed by 1,000 mg every weeks until disease progression or unacceptable toxicity. Among the 515 patients, 42% were exposed for >24 weeks and 26% were exposed for >48 weeks.Mismatch Repair Deficient (dMMR) Endometrial CancerThe safety of JEMPERLI was evaluated in GARNET in 104 patients with advanced or recurrent dMMR EC who received at least dose of JEMPERLI [see Clinical Studies (14.1)]. Patients received JEMPERLI 500 mg every weeks for doses followed by 1,000 mg every weeks as an intravenous infusion until disease progression or unacceptable toxicity. Patients with autoimmune disease that required systemic therapy within years of treatment or medical condition that required immunosuppression were ineligible. Among patients receiving JEMPERLI, 47% were exposed for months or longer and 20% were exposed for >1 year.Serious adverse reactions occurred in 34% of patients receiving JEMPERLI. Serious adverse reactions in >2% of patients included sepsis (2.9%), acute kidney injury (2.9%), urinary tract infection (2.9%), abdominal pain (2.9%), and pyrexia (2.9%).JEMPERLI was permanently discontinued due to adverse reactions in (4.8%) patients, including increased transaminases, sepsis, bronchitis, and pneumonitis. Dosage interruptions due to an adverse reaction occurred in 23% of patients who received JEMPERLI. Adverse reactions that required dosage interruption in >=1% of patients who received JEMPERLI were anemia, diarrhea, increased lipase, and pyrexia.The most common adverse reactions (>=20%) were fatigue/asthenia, nausea, diarrhea, anemia, and constipation. The most common Grade or adverse reactions (>=2%) were anemia and increased transaminases. The most common Grade or laboratory abnormalities (>=2%) were decreased lymphocytes, decreased sodium, decreased leukocytes, decreased albumin, increased creatinine, increased alkaline phosphatase and increased alanine aminotransferase.Table summarizes the adverse reactions that occurred in >=10% of patients with dMMR EC on JEMPERLI in GARNET.Table 2. Adverse Reactions (>=10%) in Patients with dMMR Endometrial Cancer Who Received JEMPERLI in GARNETToxicity was graded per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03. Includes fatigue and asthenia. Includes anemia, decreased hemoglobin, iron deficiency, and iron deficiency anemia.Adverse ReactionJEMPERLIN 104All Grades%Grade or 4%General and administration site Fatiguea 481Gastrointestinal Nausea300 Diarrhea261.9 Constipation200.9 Vomiting180Blood and lymphatic system Anemiab 2413Metabolism and nutrition Decreased appetite140Respiratory, thoracic, and mediastinal Cough140Skin and subcutaneous tissue Pruritus141Infections Urinary tract infection131.9Musculoskeletal and connective tissue Myalgia120Clinically relevant adverse reactions in <10% of patients who received JEMPERLI included:Endocrine Disorders: Hypothyroidism, hyperthyroidism, hypophysitis.Eye Disorders: Iridocyclitis.Gastrointestinal Disorders: Colitis, acute pancreatitis.General Disorders and Administration Site Conditions: Pyrexia, chills.Renal and Urinary Disorders: Nephritis.Respiratory, Thoracic, and Mediastinal Disorders: Pneumonitis.Skin and Subcutaneous Tissue Disorders: Rash, erythema, pemphigoid.Table summarizes laboratory abnormalities worsening from baseline to Grade or in >=1% of patients with dMMR EC on JEMPERLI in GARNET.Table 3. Laboratory Abnormalities that Worsened from Baseline to Grade or Occurring in >=1% of Patients with dMMR Endometrial Cancer Receiving JEMPERLI in GARNETa Consists of new onset of laboratory abnormality or worsening of baseline laboratory abnormality.Laboratory TestJEMPERLIN 104All Gradesa %Grade or 4a %Hematology Decreased lymphocytes379 Decreased leukocytes212.9Chemistry Decreased albumin302.9 Increased creatinine272.9 Increased alkaline phosphatase252.9 Increased aspartate aminotransferase161.9 Increased alanine aminotransferase152.9Electrolytes Decreased sodium264.8 Increased calcium151.9 Decreased potassium151.9Mismatch Repair Deficient Recurrent or Advanced Solid TumorsThe safety of JEMPERLI was investigated in 267 patients with recurrent or advanced dMMR solid tumors enrolled in GARNET [see Clinical Studies (14.2)]. Patients received JEMPERLI 500 mg every weeks for doses followed by 1,000 mg every weeks as an intravenous infusion until disease progression or unacceptable toxicity. Patients with autoimmune disease that required systemic therapy within years of treatment or medical condition that required immunosuppression were ineligible. The median duration of exposure to JEMPERLI was 25 weeks (range: to 139 weeks).Serious adverse reactions occurred in 34% of patients receiving JEMPERLI. Serious adverse reactions in >2% of patients included abdominal pain (3.7%), sepsis (2.6%), and acute kidney injury (2.2%). Fatal adverse reaction occurred in patient who received JEMPERLI due to respiratory failure.JEMPERLI was permanently discontinued due to adverse reactions in 9% patients; the most common adverse reaction (>1%) leading to discontinuation was increased alanine aminotransferase (1.1%).Dosage interruptions due to an adverse reaction occurred in 23% of patients who received JEMPERLI. Adverse reactions that required dosage interruption in >=1% of patients who received JEMPERLI were anemia, pneumonitis, diarrhea, adrenal insufficiency, increased alanine aminotransferase, and increased aspartate aminotransferase.The most common adverse reactions (>=20%) were fatigue/asthenia, anemia, diarrhea, and nausea. The most common Grade or adverse reactions (>=2%) were anemia, fatigue/asthenia, increased transaminases, sepsis, and acute kidney injury. The most common Grade or laboratory abnormalities (>=2%) were decreased lymphocytes, decreased sodium, increased alkaline phosphatase, and decreased albumin.Table summarizes the adverse reactions that occurred in >=10% of patients with dMMR recurrent or advanced solid tumors in GARNET.Table 4. Adverse Reactions (>=10%) in Patients with dMMR Recurrent or Advanced Solid Tumors in GARNETToxicity was graded per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03. Includes fatigue and asthenia. Includes anemia, decreased hemoglobin, iron deficiency, and iron deficiency anemia. Includes rash, rash maculopapular, rash macular, rash erythematous, rash papular, erythema, toxic skin eruption, and pemphigoid.d Includes increased alanine aminotransferase, increased aspartate aminotransferase, increased transaminases, and hypertransaminasemia.Adverse ReactionJEMPERLIN 267All Grades%Grade or 4%General and administration site Fatiguea 423.4 Pyrexia120Blood and lymphatic system Anemiab 3011Gastrointestinal Diarrhea251.5 Nausea220.4 Vomiting171.5 Constipation160.4Skin and subcutaneous tissue Pruritus150.4 Rashc 140.4Respiratory, thoracic, and mediastinal Cough130Metabolism and nutrition Decreased appetite120.4Investigations Increased transaminasesd 123Clinically relevant adverse reactions in <10% of patients who received JEMPERLI included:Endocrine Disorders: Hypothyroidism, hyperthyroidism, adrenal insufficiency, hypophysitis, autoimmune thyroiditis.Eye Disorders: Uveitis.Gastrointestinal Disorders: Colitis, enterocolitis, enterocolitis hemorrhage, pancreatitis, acute pancreatitis.General Disorders and Administration Site Conditions: Chills.Injury, Poisoning, and Procedural Complications: Infusion related reaction.Hepatobiliary Disorders: Hepatocellular injury.Musculoskeletal and Connective Tissue Disorders: Myalgia.Renal and Urinary Disorders: Nephritis, tubulointerstitial nephritis.Respiratory, Thoracic, and Mediastinal Disorders: Pneumonitis, interstitial lung disease.Table summarizes laboratory abnormalities worsening from baseline to Grade or in >=1% of patients with dMMR recurrent or advanced solid tumors in GARNET.Table 5. Laboratory Abnormalities that Worsened from Baseline to Grade or Occurring in >=1% of Patients with dMMR Recurrent or Advanced Solid Tumors in GARNETa Consists of new onset of laboratory abnormality or worsening of baseline laboratory abnormality.Laboratory TestJEMPERLIN 267All Gradesa %Grade or 4a %Hematology Decreased lymphocytes337 Decreased leukocytes181.1 Decreased neutrophils121.5Chemistry Decreased albumin262.2 Increased alkaline phosphatase 263.4 Increased aspartate aminotransferase 261.5 Increased alanine aminotransferase 221.9 Increased creatinine 211.1 Increased total bilirubin 71.5Electrolytes Decreased sodium214.9 Decreased magnesium161.1 Decreased potassium141.1 Increased potassium141.1 Increased calcium61.1 Increased magnesium4.11.5 Decreased calcium2.61.5. 6.2Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to dostarlimab-gxly in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.The immunogenicity of dostarlimab was evaluated in GARNET. Treatment-emergent anti-drug antibodies (ADAs) against dostarlimab-gxly were detected in 2.1% of 384 patients who received dostarlimab-gxly at the recommended dosage. Neutralizing antibodies were detected in 1% of patients. Because of the small number of patients who developed ADAs, the effect of immunogenicity on the efficacy and safety of dostarlimab-gxly is inconclusive.

CLINICAL STUDIES SECTION.

14CLINICAL STUDIES 14.1Mismatch Repair Deficient Recurrent or Advanced Endometrial Cancer The efficacy of JEMPERLI was evaluated in the GARNET trial (NCT02715284), multicenter, multicohort, open-label trial conducted in patients with advanced solid tumors. The efficacy population consisted of cohort of 71 patients with mismatch repair deficient (dMMR) recurrent or advanced EC who had progressed on or after treatment with platinum-containing regimen. Patients with prior treatment with PD-1/PD-L1-blocking antibodies or other immune checkpoint inhibitor therapy and patients with autoimmune disease that required systemic therapy with immunosuppressant agents within years were excluded from the trial.Patients received JEMPERLI 500 mg intravenously every weeks for doses followed by 1,000 mg intravenously every weeks. Treatment continued until disease progression or unacceptable toxicity. The major efficacy outcome measures were Overall Response Rate (ORR) and Duration of Response (DOR) as assessed by blinded independent central review (BICR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.The baseline characteristics were: median age 64 years (49% aged 65 years or older); 82% White, 3% Asian, 1% Black; and Eastern Cooperative Oncology Group Performance Status (32%) or (68%).At time of trial entry, 66% of the patients with dMMR EC had International Federation of Gynecology and Obstetrics (FIGO) Stage IV disease. The most common histology seen was endometrioid carcinoma type (70%), followed by serous (6%) and mixed and undifferentiated (2.8% each).All patients with dMMR EC had received prior anticancer treatment, with 90% of patients receiving prior anticancer surgery and 79% receiving prior anticancer radiotherapy. Approximately 40% had lines or more of prior anticancer treatment. Approximately 11% of patients had received regimens and 4% had received or more prior regimens.The dMMR tumor status was retrospectively confirmed using the VENTANA MMR RxDx Panel assay.Efficacy results are presented in Table 6.Table 6. Efficacy Results in GARNET dMMR Endometrial Cancer PopulationCI Confidence interval, = ongoing at last assessment. Median follow-up for duration of response was 14.1 months, measured from time of first response.EndpointJEMPERLIN 71Confirmed overall response rate Overall response rate42.3% (95% CI)(30.6, 54.6) Complete response rate12.7% Partial response rate29.6%Duration of response Median in monthsNot reached (range)a (2.6, 22.4+) Patients with duration >=6 months93.3%. 14.2Mismatch Repair Deficient Recurrent or Advanced Solid Tumors The efficacy of JEMPERLI was evaluated in GARNET (NCT02715284), non-randomized, multicenter, open-label, multicohort trial. The efficacy population consisted of cohort of 209 patients with dMMR recurrent or advanced solid tumors who progressed following systemic therapy and had no satisfactory alternative treatment options. Patients with dMMR endometrial cancer must have progressed on or after treatment with platinum-containing regimen. Patients with dMMR colorectal cancer must have progressed after or been intolerant to fluoropyrimidine, oxaliplatin, and irinotecan.Patients with prior treatment with PD-1/PD-L1-blocking antibodies or other immune checkpoint inhibitor therapy and patients with autoimmune disease that required systemic therapy with immunosuppressant agents within years were excluded from the trial.Patients received JEMPERLI 500 mg intravenously every weeks for doses followed by 1,000 mg intravenously every weeks. Treatment continued until disease progression or unacceptable toxicity. The major efficacy outcome measures were ORR and DOR as determined by BICR according to RECIST 1.1.The baseline characteristics were female (77%); median age 63 years (47% aged 65 years or older); 63% White, 3% Asian, 2% Black; and Eastern Cooperative Oncology Group Performance Status (39%) or (61%). At time of trial entry, 97.2% of patients (103/106) with non-endometrial dMMR solid tumors had Stage IV disease, and 68.0% (70/103) of patients with dMMR endometrial tumors had FIGO Stage IV disease.Approximately 43% of patients had received prior line of systemic anticancer treatment, 36% had received prior lines, and 21% had received or more prior lines.The dMMR tumor status was retrospectively confirmed using the VENTANA MMR RxDx Panel assay.Efficacy results are presented in Tables and 8.Table 7. Efficacy Results in GARNET dMMR Recurrent or Advanced Solid TumorsCI Confidence interval, = ongoing at last assessment. Median follow-up for duration of response was 17.5 months measured from time of first response.EndpointJEMPERLIN 209Confirmed overall response rate Overall response rate41.6% (95% CI)(34.9, 48.6) Complete response rate9.1% Partial response rate32.5%Duration of response Median in months34.7 (range)a 2.6, 35.8+ Patients with duration >=6 months95.4%Table 8. Efficacy Results in GARNET dMMR Tumor Types+ ongoing at last assessment.dMMR Mismatch Repair Deficient, ORR Overall Response Rate, DOR Duration of Response, CI Confidence Interval, EC endometrial cancer, CRC colorectal cancer, PR partial response, PD progressive disease, CR complete response, SD stable disease. Exact, 2-sided 95% CI for binomial proportion.Tumor TypePatientsNConfirmed ORR(per RECIST 1.1)DORn (%)95% CIa Range (months)EC10346 (44.7)(34.9, 54.8)2.6, 35.8+non-EC10641 (38.7)(29.4, 48.6)5.6, 30.1+ CRC6925 (36.2)(25.0, 48.7)5.6, 30.1+ Small intestinal cancer124 (33.3)(9.9, 65.1)11.1+, 28.0+ Gastric cancers83 (37.5)(8.5, 75.5)8.4+, 17.5 Pancreatic carcinoma40 (0.0)(0.0, 60.2)NA Biliary neoplasm2CR, CRNA8.4+, 13.5+ Liver cancer2PR, PDNA13.8+ Ovarian cancer2PR, SDNA25.1+ Adrenal cortical1PRNA19.5+ Breast cancer1CRNA16.8+ Esophageal cancer1PDNANA Genital neoplasm malignant female1PRNA22.2+ Pleural1PRNA15.2+ Renal cell carcinoma1SDNANA Unknown origin1PRNA20.4+.

DOSAGE & ADMINISTRATION SECTION.

2DOSAGE AND ADMINISTRATION oDose through 4: 500 mg every weeks. (2.2)oSubsequent dosing beginning weeks after Dose (Dose onwards): 1,000 mg every weeks. (2.2)oAdminister as an intravenous infusion over 30 minutes. (2.2). oDose through 4: 500 mg every weeks. (2.2). oSubsequent dosing beginning weeks after Dose (Dose onwards): 1,000 mg every weeks. (2.2). oAdminister as an intravenous infusion over 30 minutes. (2.2). 2.1Patient Selection. Mismatch Repair Deficient Recurrent or Advanced Endometrial Cancer or Mismatch Repair Deficient Recurrent or Advanced Solid TumorsSelect patients for treatment with JEMPERLI based on the presence of dMMR in tumor specimens [see Clinical Studies (14)]. 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.. 2.2Recommended Dosage The recommended dosage of JEMPERLI is:oDose through Dose 4: 500 mg every weeksoSubsequent dosing beginning weeks after Dose (Dose onwards): 1,000 mg every weeksAdminister JEMPERLI as an intravenous infusion over 30 minutes. Treat patients until disease progression or unacceptable toxicity.. oDose through Dose 4: 500 mg every weeks. oSubsequent dosing beginning weeks after Dose (Dose onwards): 1,000 mg every weeks. 2.3Dosage 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 1.Table 1. Recommended Dosage Modifications for Adverse ReactionsAST aspartate aminotransferase, ALT alanine aminotransferase, ULN upper limit of normal, SJS Stevens-Johnson syndrome, TEN toxic epidermal necrolysis, DRESS drug rash with eosinophilia and systemic symptoms. Based on National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0. Resume in patients with complete or partial resolution (Grade 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. If 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 ReactionSeveritya Dosage ModificationImmune-Mediated Adverse Reactions [see Warnings and Precautions (5.1)] PneumonitisGrade 2Withholdb Grade or or recurrent Grade 2Permanently discontinueColitisGrade or 3Withholdb Grade 4Permanently discontinueHepatitis with no tumor involvement of the liverAST or ALT increases to more than and up to times ULNor Total bilirubin increases to more than 1.5 and up to times ULNWithholdb AST or ALT increases to more than times ULNor Total bilirubin increases to more than times ULNPermanently discontinueHepatitis with tumor involvement of the liverc Baseline AST or ALT is more than and up to times ULN and increases to more than and up to 10 times ULNorBaseline AST or ALT is more than and up to times ULN and increases to more than and up to 10 times ULNWithholdb AST or ALT increases to more than 10 times ULNor Total bilirubin increases to more than times ULNPermanently discontinueEndocrinopathiesGrade 2, 3, or 4Withhold until clinically stable or permanently discontinue, depending on severityb Nephritis with renal dysfunctionGrade or increased blood creatinineWithholdb Grade increased blood creatinine Permanently discontinueExfoliative dermatologic conditionsSuspected SJS, TEN, or DRESSWithholdb Confirmed SJS, TEN, or DRESSPermanently discontinueMyocarditisGrade 2, 3, or 4Permanently discontinueNeurological toxicitiesGrade 2Withholdb Grade or 4Permanently discontinueOther Adverse ReactionsInfusion-related reactions [see Warnings and Precautions (5.2)] Grade or 2Interrupt or slow the rate of infusionGrade or 4Permanently discontinue. 2.4Preparation and Administration Preparation for Intravenous InfusionoVisually inspect the solution for particulate matter and discoloration. The solution is clear to slightly opalescent, colorless to yellow. Discard the vial if visible particles are observed.oDo not shake.oFor the 500-mg dose, withdraw 10 mL of JEMPERLI from vial using disposable sterile syringe made of polypropylene and dilute into an intravenous infusion bag containing 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to final concentration between to 10 mg/mL (maximum 250 mL). JEMPERLI is compatible with an infusion bag made of polyolefin, ethylene vinyl acetate, or polyvinyl chloride with di(2-ethylhexyl) phthalate (DEHP).oFor the 1,000-mg dose, withdraw 10 mL from each of vials (withdraw 20 mL total) and dilute into an intravenous bag containing 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to final concentration between to 10 mg/mL (maximum 250 mL).oMix diluted solution by gentle inversion. Do not shake.oDiscard any unused portion left in the vial.Storage of Infusion SolutionStore in the original carton until time of preparation in order to protect from light. The prepared dose may be stored either:oAt room temperature for no more than hours from the time of preparation until the end of infusion.oUnder refrigeration at 2C to 8C (36oF to 46oF) for no more than 24 hours from time of preparation until end of infusion. If refrigerated, allow the diluted solution to come to room temperature prior to administration.Discard after hours at room temperature or after 24 hours under refrigeration.Do not freeze.AdministrationAdminister infusion solution intravenously over 30 minutes through an intravenous line using tubing made of polyvinyl chloride or platinum cured silicon; fittings made of polyvinyl chloride or polycarbonate; and sterile, non-pyrogenic, low-protein binding, 0.2-micron, in-line or add-on filter.JEMPERLI must not be administered as an intravenous push or bolus injection. Do not co-administer other drugs through the same infusion line.. oVisually inspect the solution for particulate matter and discoloration. The solution is clear to slightly opalescent, colorless to yellow. Discard the vial if visible particles are observed.. oDo not shake.. oFor the 500-mg dose, withdraw 10 mL of JEMPERLI from vial using disposable sterile syringe made of polypropylene and dilute into an intravenous infusion bag containing 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to final concentration between to 10 mg/mL (maximum 250 mL). JEMPERLI is compatible with an infusion bag made of polyolefin, ethylene vinyl acetate, or polyvinyl chloride with di(2-ethylhexyl) phthalate (DEHP).. oFor the 1,000-mg dose, withdraw 10 mL from each of vials (withdraw 20 mL total) and dilute into an intravenous bag containing 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to final concentration between to 10 mg/mL (maximum 250 mL).. oMix diluted solution by gentle inversion. Do not shake.. oDiscard any unused portion left in the vial.. oAt room temperature for no more than hours from the time of preparation until the end of infusion.. oUnder refrigeration at 2C to 8C (36oF to 46oF) for no more than 24 hours from time of preparation until end of infusion. If refrigerated, allow the diluted solution to come to room temperature prior to administration.

INFORMATION FOR PATIENTS SECTION.

17PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide).Immune-Mediated Adverse ReactionsInform patients of the risk of immune-mediated adverse reactions that may be severe or fatal, may occur after discontinuation of treatment, and may require corticosteroid or other treatment and interruption or discontinuation of JEMPERLI. These reactions may include:oPneumonitis: Advise patients to contact their healthcare provider immediately for new or worsening cough, chest pain, or shortness of breath [see Warnings and Precautions (5.1)].oColitis: Advise patients to contact their healthcare provider immediately for diarrhea or severe abdominal pain [see Warnings and Precautions (5.1)].oHepatitis: Advise patients to contact their healthcare provider immediately for jaundice, severe nausea or vomiting, or easy bruising or bleeding [see Warnings and Precautions (5.1)].oImmune-mediated endocrinopathies: Advise patients to contact their healthcare provider immediately for signs or symptoms of hypothyroidism, hyperthyroidism, thyroiditis, adrenal insufficiency, hypophysitis, or type diabetes mellitus [see Warnings and Precautions (5.1)].oNephritis: Advise patients to contact their healthcare provider immediately for signs or symptoms of nephritis [see Warnings and Precautions (5.1)].oSevere skin reactions: Advise patients to contact their healthcare provider immediately for any signs or symptoms of severe skin reactions, SJS, TEN, or DRESS [see Warnings and Precautions (5.1)].oOther immune-mediated adverse reactions:oAdvise patients that immune-mediated adverse reactions can occur and may involve any organ system, and to contact their healthcare provider immediately for any new signs or symptoms [see Warnings and Precautions (5.1)].oAdvise patients of the risk of solid organ transplant rejection and to contact their healthcare provider immediately for signs or symptoms of organ transplant rejection [see Warnings and Precautions (5.1)].Infusion-Related ReactionsoAdvise patients to contact their healthcare provider immediately for signs or symptoms of infusion-related reactions [see Warnings and Precautions (5.2)].Complications of Allogeneic HSCT oAdvise patients of the risk of post-allogeneic hematopoietic stem cell transplantation complications [see Warnings and Precautions (5.3)].Embryo-Fetal ToxicityoAdvise females of reproductive potential of the potential risk to fetus and to inform their healthcare provider of known or suspected pregnancy [see Warnings and Precautions (5.4), Use in Specific Populations (8.1, 8.3)].oAdvise females of reproductive potential to use effective contraception during treatment with JEMPERLI and for months after the last dose [see Warnings and Precautions (5.4), Use in Specific Populations (8.1, 8.3)].LactationoAdvise women not to breastfeed during treatment with JEMPERLI and for months after the last dose [see Use in Specific Populations (8.2)].Trademarks are owned by or licensed to the GSK group of companies.Manufactured byGlaxoSmithKline LLCPhiladelphia, PA 19112U.S. License No. 1727Distributed byGlaxoSmithKlineResearch Triangle Park, NC 27709(C)2021 GSK group of companies or its licensor.JMP:2PI. oPneumonitis: Advise patients to contact their healthcare provider immediately for new or worsening cough, chest pain, or shortness of breath [see Warnings and Precautions (5.1)].. oColitis: Advise patients to contact their healthcare provider immediately for diarrhea or severe abdominal pain [see Warnings and Precautions (5.1)].. oHepatitis: Advise patients to contact their healthcare provider immediately for jaundice, severe nausea or vomiting, or easy bruising or bleeding [see Warnings and Precautions (5.1)].. oImmune-mediated endocrinopathies: Advise patients to contact their healthcare provider immediately for signs or symptoms of hypothyroidism, hyperthyroidism, thyroiditis, adrenal insufficiency, hypophysitis, or type diabetes mellitus [see Warnings and Precautions (5.1)].. oNephritis: Advise patients to contact their healthcare provider immediately for signs or symptoms of nephritis [see Warnings and Precautions (5.1)].. oSevere skin reactions: Advise patients to contact their healthcare provider immediately for any signs or symptoms of severe skin reactions, SJS, TEN, or DRESS [see Warnings and Precautions (5.1)].. oOther immune-mediated adverse reactions:oAdvise patients that immune-mediated adverse reactions can occur and may involve any organ system, and to contact their healthcare provider immediately for any new signs or symptoms [see Warnings and Precautions (5.1)].oAdvise patients of the risk of solid organ transplant rejection and to contact their healthcare provider immediately for signs or symptoms of organ transplant rejection [see Warnings and Precautions (5.1)].. oAdvise patients that immune-mediated adverse reactions can occur and may involve any organ system, and to contact their healthcare provider immediately for any new signs or symptoms [see Warnings and Precautions (5.1)].. oAdvise patients of the risk of solid organ transplant rejection and to contact their healthcare provider immediately for signs or symptoms of organ transplant rejection [see Warnings and Precautions (5.1)].. oAdvise patients to contact their healthcare provider immediately for signs or symptoms of infusion-related reactions [see Warnings and Precautions (5.2)].. oAdvise patients of the risk of post-allogeneic hematopoietic stem cell transplantation complications [see Warnings and Precautions (5.3)].. oAdvise females of reproductive potential of the potential risk to fetus and to inform their healthcare provider of known or suspected pregnancy [see Warnings and Precautions (5.4), Use in Specific Populations (8.1, 8.3)].. oAdvise females of reproductive potential to use effective contraception during treatment with JEMPERLI and for months after the last dose [see Warnings and Precautions (5.4), Use in Specific Populations (8.1, 8.3)].. oAdvise women not to breastfeed during treatment with JEMPERLI and for months after the last dose [see Use in Specific Populations (8.2)].

SPL MEDGUIDE SECTION.

MEDICATION GUIDEJEMPERLI (jem-PER-lee)(dostarlimab-gxly)injectionWhat is the most important information should know about JEMPERLIJEMPERLI is medicine that may treat certain cancers by working with your immune system. JEMPERLI can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during treatment or even after your treatment has ended.Call or see your healthcare provider right away if you develop any new or worsening signs or symptoms, including:Lung problems.ocoughoshortness of breathochest painIntestinal problems.odiarrhea or more bowel movements than usualostools that are black, tarry, sticky, or have blood or mucusosevere stomach-area (abdomen) pain or tendernessLiver problems.oyellowing of your skin or the whites of your eyesosevere nausea or vomitingopain on the right side of your stomach area (abdomen)odark urine (tea colored)obleeding or bruising more easily than usualHormone gland problems.oheadaches that will not go away or unusual headachesoeye sensitivity to lightoeye problems orapid heartbeatoincreased sweatingoextreme tirednessoweight gain or weight lossofeeling more hungry or thirsty than usualourinating more often than usualohair lossofeeling coldoconstipationoyour voice gets deeperodizziness or faintingochanges in mood or behavior, such as decreased sex drive, irritability, or forgetfulnessKidney problems.ochange in the amount or color of your urineoblood in your urineoswelling in your anklesoloss of appetiteSkin problems.orashoitchingoskin blistering or peelingopainful sores or ulcers in your mouth or in your nose, throat, or genital areaofever or flu-like symptomsoswollen lymph nodesProblems can also happen in other organs and tissues. These are not all of the signs and symptoms of immune system problems that can happen with JEMPERLI. Call or see your healthcare provider right away for any new or worse signs or symptoms.ochest pain, irregular heartbeat, shortness of breath, swelling of anklesoconfusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legsodouble vision, blurry vision, sensitivity to light, eye pain, changes in eyesightopersistent or severe muscle pain or weakness, muscle crampsolow red blood cells, bruisingInfusion reactions that can sometimes be severe or life-threatening. Signs and symptoms of infusion reactions may include:ochills or shakingoitching or rashoflushingoshortness of breath or wheezingodizzinessofeel like passing outofeveroback or neck painRejection of transplanted organ. Your healthcare provider should tell you what signs and symptoms you should report and monitor you, depending on the type of organ transplant that you have had.Complications, including graft-versus-host-disease (GVHD), in people who have received bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with JEMPERLI. Your healthcare provider will monitor you for these complications.Getting medical treatment right away may help keep these problems from becoming more serious.Your healthcare provider will check you for these problems during treatment with JEMPERLI. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may also need to delay or completely stop treatment with JEMPERLI, if you have severe side effects.What is JEMPERLIJEMPERLI is prescription medicine used to treat adults with certain cancers that have been shown by laboratory test to be mismatch repair deficient (dMMR), and your cancer has returned, or it has spread or cannot be removed by surgery (advanced cancer). JEMPERLI may be used when:oyou have kind of uterine cancer called endometrial cancer, and you have received chemotherapy that contains platinum and it did not work or is no longer working. oyou have solid tumor that progressed during treatment or after treatment, and you have no satisfactory treatment options.It is not known if JEMPERLI is safe and effective in children.Before you receive JEMPERLI, tell your healthcare provider if you have any medical conditions, including if you:ohave immune system problems, such as Crohns disease, ulcerative colitis, or lupus.ohave received an organ transplant.ohave received or plan to receive stem cell transplant that uses donor stem cells (allogeneic).ohave received radiation treatment to your chest area.ohave condition that affects your nervous system, such as myasthenia gravis or Guillain-Barre syndrome.oare pregnant or plan to become pregnant. JEMPERLI can harm your unborn baby. Females who are able to become pregnant:oYour healthcare provider will do pregnancy test before you start treatment with JEMPERLI.oYou should use an effective method of birth control during your treatment and for months after your last dose of JEMPERLI. Talk to your healthcare provider about birth control methods that you can use during this time.oTell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with JEMPERLI.oare breastfeeding or plan to breastfeed. It is not known if JEMPERLI passes into your breast milk. Do not breastfeed during treatment and for months after your last dose of JEMPERLI.Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.How will receive JEMPERLIoYour healthcare provider will give you JEMPERLI into your vein through an intravenous (IV) line over 30 minutes.oJEMPERLI is usually given every weeks for the first doses, and then beginning weeks later, it is usually given every weeks.oYour healthcare provider will decide how many treatments you need.oYour healthcare provider will do blood tests to check you for side effects.oIf you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment.What are the possible side effects of JEMPERLIJEMPERLI can cause serious side effects. oSee What is the most important information should know about JEMPERLIThe most common side effects of JEMPERLI in people with dMMR solid tumors include:otiredness and weaknessolow red blood cell count (anemia)odiarrheaonauseaodecreased number of certain white blood cellsodecreased albumin in the bloodoincrease in certain liver blood testsodecreased salt (sodium) in the bloodThese are not all the possible side effects of JEMPERLI. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.General information about the safe and effective use of JEMPERLI.Medicines are sometimes prescribed for purposes other than those listed in Medication Guide. If you would like more information about JEMPERLI, talk with your healthcare provider. You can ask your healthcare provider for information about JEMPERLI that is written for healthcare professionals.What are the ingredients in JEMPERLIActive ingredient: dostarlimab-gxlyInactive ingredients: citric acid monohydrate, L-arginine hydrochloride, polysorbate 80, sodium chloride, trisodium citrate dihydrate, and Water for Injection.For more information, call 1-888-825-5249 or go to www.gsk.com.Trademarks are owned by or licensed to the GSK group of companies.Manufactured by:GlaxoSmithKline LLC, Philadelphia, PA 19112, U.S. License No. 1727Distributed by:GlaxoSmithKline, Research Triangle Park, NC 27709 (C)2021 GSK group of companies or its licensor.JMP:2MG This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: August 2021. ocough. oshortness of breath. ochest pain. odiarrhea or more bowel movements than usual. ostools that are black, tarry, sticky, or have blood or mucus. osevere stomach-area (abdomen) pain or tenderness. oyellowing of your skin or the whites of your eyes. osevere nausea or vomiting. opain on the right side of your stomach area (abdomen). odark urine (tea colored). obleeding or bruising more easily than usual. oheadaches that will not go away or unusual headaches. oeye sensitivity to light. oeye problems orapid heartbeat. oincreased sweating. oextreme tiredness. oweight gain or weight loss. ofeeling more hungry or thirsty than usual. ourinating more often than usual. ohair loss. ofeeling cold. oconstipation. oyour voice gets deeper. odizziness or fainting. ochanges in mood or behavior, such as decreased sex drive, irritability, or forgetfulness. ochange in the amount or color of your urine. oblood in your urine. oswelling in your ankles. oloss of appetite. orash. oitching. oskin blistering or peeling. opainful sores or ulcers in your mouth or in your nose, throat, or genital area. ofever or flu-like symptoms. oswollen lymph nodes. ochest pain, irregular heartbeat, shortness of breath, swelling of ankles. oconfusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs. odouble vision, blurry vision, sensitivity to light, eye pain, changes in eyesight. opersistent or severe muscle pain or weakness, muscle cramps. olow red blood cells, bruising. ochills or shaking. oitching or rash. oflushing. oshortness of breath or wheezing. odizziness. ofeel like passing out. ofever. oback or neck pain. oyou have kind of uterine cancer called endometrial cancer, and you have received chemotherapy that contains platinum and it did not work or is no longer working. oyou have solid tumor that progressed during treatment or after treatment, and you have no satisfactory treatment options.. ohave immune system problems, such as Crohns disease, ulcerative colitis, or lupus.. ohave received an organ transplant.. ohave received or plan to receive stem cell transplant that uses donor stem cells (allogeneic).. ohave received radiation treatment to your chest area.. ohave condition that affects your nervous system, such as myasthenia gravis or Guillain-Barre syndrome.. oare pregnant or plan to become pregnant. JEMPERLI can harm your unborn baby.. Females who are able to become pregnant:oYour healthcare provider will do pregnancy test before you start treatment with JEMPERLI.oYou should use an effective method of birth control during your treatment and for months after your last dose of JEMPERLI. Talk to your healthcare provider about birth control methods that you can use during this time.oTell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with JEMPERLI.. oYour healthcare provider will do pregnancy test before you start treatment with JEMPERLI.. oYou should use an effective method of birth control during your treatment and for months after your last dose of JEMPERLI. Talk to your healthcare provider about birth control methods that you can use during this time.. oTell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with JEMPERLI.. oare breastfeeding or plan to breastfeed. It is not known if JEMPERLI passes into your breast milk. Do not breastfeed during treatment and for months after your last dose of JEMPERLI.. oYour healthcare provider will give you JEMPERLI into your vein through an intravenous (IV) line over 30 minutes.. oJEMPERLI is usually given every weeks for the first doses, and then beginning weeks later, it is usually given every weeks.. oYour healthcare provider will decide how many treatments you need.. oYour healthcare provider will do blood tests to check you for side effects.. oIf you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment.. oSee What is the most important information should know about JEMPERLI. otiredness and weakness. olow red blood cell count (anemia). odiarrhea. onausea. odecreased number of certain white blood cells. odecreased albumin in the blood. oincrease in certain liver blood tests. odecreased salt (sodium) in the blood. This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: August 2021.

USE IN SPECIFIC POPULATIONS SECTION.

8USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. (8.2). 8.1Pregnancy Risk SummaryBased on its mechanism of action, JEMPERLI can cause fetal harm when administered to pregnant woman [see Clinical Pharmacology (12.1)]. 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 Data). 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 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.DataAnimal Data: Animal reproduction studies have not been conducted with JEMPERLI to evaluate its effect on reproduction and fetal development. 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.. 8.2Lactation Risk SummaryThere is no information regarding the presence of dostarlimab-gxly in human milk or its effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed child, advise women not to breastfeed during treatment and for months after the last dose of JEMPERLI.. 8.3Females and Males of Reproductive Potential JEMPERLI can cause fetal harm when administered to pregnant woman [see Use in Specific Populations (8.1)].Pregnancy TestingVerify pregnancy status in females of reproductive potential prior to initiating JEMPERLI [see Use in Specific Populations (8.1)]. ContraceptionFemales: Advise females of reproductive potential to use effective contraception during treatment with JEMPERLI and for months after the last dose.. 8.4Pediatric Use The safety and efficacy of JEMPERLI have not been established in pediatric patients.. 8.5Geriatric Use Of the 515 patients treated with JEMPERLI, 51% were younger than 65 years, 37% were aged 65 through 75 years, and 12% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.

WARNINGS AND PRECAUTIONS SECTION.

5WARNINGS AND PRECAUTIONS oImmune-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, 5.1)oInfusion-related reactions: Interrupt, slow the rate of infusion, or permanently discontinue JEMPERLI based on severity of reaction. (2.3, 5.2)oComplications 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 PD-1/PD-L1-blocking antibody. (5.3)oEmbryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to fetus and to use effective contraception. (5.4, 8.1, 8.3). oImmune-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, 5.1). oInfusion-related reactions: Interrupt, slow the rate of infusion, or permanently discontinue JEMPERLI based on severity of reaction. (2.3, 5.2). oComplications 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 PD-1/PD-L1-blocking antibody. (5.3). oEmbryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to fetus and to use effective contraception. (5.4, 8.1, 8.3). 5.1Severe and Fatal Immune-Mediated Adverse Reactions JEMPERLI is monoclonal antibody that belongs to class of drugs that bind to either the programmed death receptor-1 (PD-1) or PD-ligand (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 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 (2.3)]. In general, if JEMPERLI requires interruption or discontinuation, administer systemic corticosteroids (1 to mg/kg/day prednisone or equivalent) until improvement to Grade or less. Upon improvement to Grade or less, initiate corticosteroid taper and continue to taper over at least 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 PneumonitisJEMPERLI 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 1.4% (7/515) of patients receiving JEMPERLI, including Grade (1.2%) and Grade (0.2%) pneumonitis. Pneumonitis led to discontinuation of JEMPERLI in 0.6% patients.Systemic corticosteroids were required in all patients with pneumonitis. Pneumonitis resolved in 86% of the patients. Two patients reinitiated JEMPERLI after symptom improvement; of these, patient had recurrence of pneumonitis.Immune-Mediated ColitisJEMPERLI 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 1.4% (7/515) of patients receiving JEMPERLI, including Grade (0.8%) and Grade (0.6%) adverse reactions. Colitis led to discontinuation of JEMPERLI in (0.2%) patient.Systemic corticosteroids were required in 29% (2/7) of patients with colitis. Colitis resolved in 71% of the patients. Of the patients in whom JEMPERLI was withheld for colitis, all reinitiated treatment with JEMPERLI.Immune-Mediated HepatitisJEMPERLI can cause immune-mediated hepatitis, which can be fatal.Immune-mediated hepatitis occurred in 0.2% (1/515) of patients receiving JEMPERLI, which was Grade 3. Systemic corticosteroids were required and the event resolved.Immune-Mediated EndocrinopathiesAdrenal Insufficiency: JEMPERLI can cause primary or secondary adrenal insufficiency. For Grade 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 (2.3)].Adrenal insufficiency occurred in 1.4% (7/515) patients receiving JEMPERLI, including Grade (0.8%) and Grade (0.6%). Adrenal insufficiency resulted in discontinuation in (0.2%) patient and resolved in 29% of the patients.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 (2.3)].Thyroid Disorders: JEMPERLI can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement or medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity [see Dosage and Administration (2.3)].Thyroiditis: Thyroiditis occurred in 0.4% (2/515) of patients receiving JEMPERLI; both were Grade 2. Neither event of thyroiditis resolved; there were no discontinuations of JEMPERLI due to thyroiditis.Hypothyroidism: Hypothyroidism occurred in 7.2% (37/515) of patients receiving JEMPERLI, all of which were Grade 2. Hypothyroidism did not lead to discontinuation of JEMPERLI and resolved in 35% of the 37 patients. Systemic corticosteroids were not required for any of the 37 patients with hypothyroidism.Hyperthyroidism: Hyperthyroidism occurred in 1.9% (10/515) of patients receiving JEMPERLI, including Grade (1.7%) and Grade (0.2%). Hyperthyroidism did not lead to discontinuation of JEMPERLI and resolved in 80% of the 10 patients. Systemic corticosteroids were not required for any of the 10 patients with hyperthyroidism.Type Diabetes Mellitus, Which Can Present with Diabetic Ketoacidosis: JEMPERLI can cause type 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 (2.3)].Immune-Mediated Nephritis with Renal DysfunctionJEMPERLI can cause immune-mediated nephritis, which can be fatal. Nephritis occurred in 0.4% (2/515) of patients receiving JEMPERLI; both were Grade 2. Nephritis did not lead to discontinuation of JEMPERLI and resolved in both patients. Systemic corticosteroids were required in of the patients experiencing nephritis.Immune-Mediated Dermatologic Adverse ReactionsJEMPERLI 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 (2.3)].Other Immune-Mediated Adverse ReactionsThe following clinically significant immune-mediated adverse reactions occurred in <1% of the 515 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-Barre 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 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.. 5.2Infusion-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% (1/515) 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 (2.3)].. 5.3Complications 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 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 PD-1/PD-L1-blocking antibody prior to or after an allogeneic HSCT.. 5.4Embryo-Fetal Toxicity. Based on its mechanism of action, JEMPERLI can cause fetal harm when administered to 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 fetus. Advise females of reproductive potential to use effective contraception during treatment with JEMPERLI and for months after the last dose [see Use in Specific Populations (8.1, 8.3)].