Dostarlimab

1 INDICATIONS AND USAGE JEMPERLI is a programmed death receptor-1 (PD-1)–blocking antibody indicated: Endometrial Cancer • 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 ) • 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 , 2.1 ) Mismatch Repair Deficient Recurrent or Advanced Solid Tumors • 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 , 2.1 ) 1 This 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). ( 1.2 ) 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 )]. 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 ( 2.1 )]. This indication is approved under accelerated approval based on tumor response rate and durability of response [see Clinical Studies ( 14.2 )]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

2 DOSAGE AND ADMINISTRATION • 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 ) • 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 ) • 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 ) • Administer as an intravenous infusion over 30 minutes. ( 2.2 ) • For complete dosing instructions, see full prescribing information. 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 ( 14.1 )] . • recurrent or advanced solid tumors [see Clinical Studies ( 14.2 )] . 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. 2.2 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. a 30-minute intravenous infusion. b Refer 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 mg a JEMPERLI every 3 weeks for 6 cycles in combination with carboplatin and paclitaxel b followed 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 mg a JEMPERLI every 3 weeks for 4 cycles followed by 1,000 mg a JEMPERLI every 6 weeks for all cycles thereafter. Until disease progression or unacceptable toxicity. 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. a Based on National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0. b Resume 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. c 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 Reaction Severity a Dosage Modification Immune-Mediated Adverse Reactions [see Warnings and Precautions ( 5.1 )] Pneumonitis Grade 2 Withhold b Grade 3 or 4 or recurrent Grade 2 Permanently discontinue Colitis Grade 2 or 3 Withhold b 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 Withhold b AST or ALT increases to more than 8 times ULN or Total bilirubin increases to more than 3 times ULN Permanently discontinue Hepatitis with tumor involvement of the liver c Baseline AST or ALT is more than 1 and up to 3 times ULN and increases to more than 5 and up to 10 times ULN or Baseline AST or ALT is more than 3 and up to 5 times ULN and increases to more than 8 and up to 10 times ULN Withhold b 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 severity b Nephritis with renal dysfunction Grade 2 or 3 increased blood creatinine Withhold b Grade 4 increased blood creatinine Permanently discontinue Exfoliative dermatologic conditions Suspected SJS, TEN, or DRESS Withhold b Confirmed SJS, TEN, or DRESS Permanently discontinue Myocarditis Grade 2, 3, or 4 Permanently discontinue Neurological toxicities Grade 2 Withhold b Grade 3 or 4 Permanently discontinue Other Adverse Reactions Infusion-related reactions [see Warnings and Precautions ( 5.2 )] Grade 1 or 2 Interrupt or slow the rate of infusion Grade 3 or 4 Permanently discontinue 2.4 Preparation and Administration Preparation for Intravenous Infusion • Visually inspect the solution for particulate matter and discoloration. The solution is clear to slightly opalescent, colorless to yellow. Discard the vial if visible particles are observed. • Do not shake. • JEMPERLI is compatible with an infusion bag made of polyolefin, ethylene vinyl acetate, or polyvinyl chloride with di(2-ethylhexyl) phthalate (DEHP). • For the 500-mg dose, withdraw 10 mL of JEMPERLI from a vial using a 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 a final concentration between 2 to 10 mg/mL (maximum 250 mL). • For the 1,000-mg dose, withdraw 10 mL from each of 2 vials (withdraw 20 mL total) and dilute into an intravenous bag containing 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to a final concentration between 4 to 10 mg/mL (maximum 250 mL). • Mix diluted solution by gentle inversion. Do not shake. • Discard any unused portion left in the vial. Storage of Infusion Solution Store in the original carton until time of preparation in order to protect from light. The prepared dose may be stored either: • At room temperature for no more than 6 hours from the time of preparation until the end of infusion. • Under refrigeration at 2°C to 8°C (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 6 hours at room temperature or after 24 hours under refrigeration. Do not freeze. Administration Administer 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 a 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.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Severe and fatal immune-mediated adverse reactions [see Warnings and Precautions ( 5.1 )] • Infusion-related reactions [see Warnings and Precautions ( 5.2 )] • Most common adverse reactions (≥20%), including laboratory abnormalities, with JEMPERLI in combination with carboplatin and paclitaxel in patients with EC are decreased hemoglobin, increased creatinine, peripheral neuropathy, decreased white blood cell count, fatigue, nausea, alopecia, decreased platelets, increased glucose, decreased lymphocytes, decreased magnesium, decreased neutrophils, increased aspartate aminotransferase (AST), arthralgia, rash, constipation, diarrhea, increased alanine aminotransferase (ALT), decreased potassium, decreased albumin, decreased sodium, increased alkaline phosphatase, abdominal pain, dyspnea, decreased appetite, increased amylase, decreased phosphate, urinary tract infection, and vomiting. ( 6.1 ) • Most common adverse reactions (≥20%) with JEMPERLI as a single agent in patients with dMMR solid tumors are fatigue/asthenia, anemia, diarrhea, and nausea. Most common Grade 3 or 4 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 . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety population described in the Warnings and Precautions for use of JEMPERLI in combination with carboplatin and paclitaxel was evaluated in 241 patients with primary advanced or recurrent EC in the randomized, double-blind, active-controlled RUBY trial. Additionally, the pooled safety population described in Warnings and Precautions reflects exposure to JEMPERLI as a single agent in 605 patients with advanced or recurrent solid tumors in the non-randomized, open-label, multicohort GARNET trial that enrolled 314 patients with EC and 291 patients with other solid tumors. JEMPERLI was administered intravenously at doses of 500 mg every 3 weeks for 4 cycles followed by 1,000 mg every 6 weeks until disease progression or unacceptable toxicity. Among the 605 patients, 32% were exposed for >1 year and 19% were exposed for >2 years. Primary Advanced or Recurrent Endometrial Cancer: JEMPERLI in Combination with Carboplatin and Paclitaxel The safety of JEMPERLI in patients with primary advanced or recurrent EC was evaluated in RUBY [see Clinical Studies (14.1)] . Patients received JEMPERLI 500 mg (n = 241) or placebo (n = 246) in combination with carboplatin and paclitaxel every 3 weeks for 6 cycles followed by JEMPERLI 1,000 mg or placebo every 6 weeks until disease progression or unacceptable toxicity. Among the 241 patients, 38.6% were exposed for >1 year and 24.1% were exposed for >2 years. Serious adverse reactions occurred in 39% of patients receiving JEMPERLI in combination with carboplatin and paclitaxel; the most common serious adverse reactions were sepsis, including urosepsis (3.7%), and pulmonary embolism (3.3%). Fatal adverse reactions occurred in 1.2% of patients receiving JEMPERLI including septic shock (0.8%) and myelosuppression (0.4%). In patients receiving JEMPERLI in combination with carboplatin and paclitaxel, JEMPERLI was permanently discontinued due to adverse reactions in 46 patients (19%). Adverse reactions that required permanent discontinuation in ≥2 patients included 3 cases (1.2%) of rash maculo-papular, and 2 cases (0.8%) each of increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), diarrhea, pancreatitis, fatigue, pneumonitis, and arthralgia. Dosage interruptions due to an adverse reaction occurred in 37% of patients who received JEMPERLI in combination with carboplatin and paclitaxel. Adverse reactions that required dosage interruption in ≥5% of patients who received JEMPERLI in combination with carboplatin and paclitaxel were anemia, thrombocytopenia, and peripheral neuropathy. The most common adverse reactions, including laboratory abnormalities (≥20%), were decreased hemoglobin, increased creatinine, peripheral neuropathy, decreased white blood cell count, fatigue, nausea, alopecia, decreased platelets, increased glucose, decreased lymphocytes, decreased magnesium, decreased neutrophils, increased AST, arthralgia, rash, constipation, diarrhea, increased ALT, decreased potassium, decreased albumin, decreased sodium, increased alkaline phosphatase, abdominal pain, dyspnea, decreased appetite, increased amylase, decreased phosphate, urinary tract infection, and vomiting. Table 3 summarizes the adverse reactions that occurred in ≥20% of patients with primary advanced or recurrent EC receiving JEMPERLI in combination with carboplatin and paclitaxel in RUBY. Table 3. Adverse Reactions (≥20%) in Patients with Endometrial Cancer Who Received JEMPERLI with Carboplatin and Paclitaxel in RUBY Graded per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03. a Includes neuropathy peripheral and peripheral sensory neuropathy. b Includes fatigue and asthenia. c Includes abdominal pain, abdominal pain upper, abdominal pain lower, gastrointestinal pain, abdominal discomfort, epigastric discomfort, and abdominal tenderness. d Includes rash, rash maculo-papular, palmar-plantar erythrodysesthesia syndrome, rash pustular, skin exfoliation, and vulvovaginal rash. e Includes dyspnea and dyspnea exertional. f Includes urinary tract infection, urinary tract infection bacterial, cystitis, and pyelonephritis. Adverse Reaction JEMPERLI with Carboplatin and Paclitaxel N = 241 Placebo withCarboplatin and Paclitaxel N = 246 All Grades % Grade 3 or 4 % All Grades % Grade 3 or 4 % Nervous System Disorders Peripheral neuropathy a 64 4.1 61 2.0 General Fatigue b 56 3.3 63 5 Gastrointestinal Disorders Nausea 54 2.9 46 1.6 Constipation 35 0.4 36 0 Diarrhea 32 1.7 29 0.8 Abdominal pain c 24 2.5 29 2 Vomiting 20 1.7 20 1.6 Skin and Subcutaneous Tissue Alopecia 54 0 50 1.2 Rash d 37 7 18 1.2 Musculoskeletal and Connective Tissue Arthralgia 37 1.2 35 0.4 Respiratory, Thoracic and Mediastinal Disorders Dyspnea e 23 1.7 26 0.8 Metabolism and Nutrition Disorders Decreased appetite 22 2.1 18 0.4 Infections and Infestations Urinary tract infection f 21 3.3 18 1.6 Clinically relevant adverse reactions in <20% of patients with primary advanced or recurrent EC who received JEMPERLI in combination with carboplatin and paclitaxel included: Endocrine Disorders: Hypothyroidism, hyperthyroidism, thyroiditis, adrenal insufficiency. Eye Disorders: Keratitis, uveitis. Gastrointestinal Disorders: Colitis, pancreatitis. Metabolism and Nutrition Disorders: Type 1 diabetes mellitus. Musculoskeletal and Connective Tissue Disorders: Immune-mediated arthritis. Respiratory, Thoracic, and Mediastinal Disorders: Pneumonitis. Cardiac Disorders: Myocarditis. Nervous System Disorders: Encephalopathy. Vascular Disorders: Hypertension, hemorrhage. Table 4 summarizes the laboratory abnormalities in patients with primary advanced or recurrent EC receiving JEMPERLI in combination with carboplatin and paclitaxel in RUBY. Table 4. Select Laboratory Abnormalities that Worsened from Baseline Occurring in ≥20% of Patients with Endometrial Cancer Receiving JEMPERLI with Carboplatin and Paclitaxel in RUBY ALT = alanine aminotransferase; AST = aspartate aminotransferase. a Consists of new onset of laboratory abnormality or worsening of baseline laboratory abnormality. Laboratory Test JEMPERLI with Carboplatin and Paclitaxel N = 241 Placebo with Carboplatin and Paclitaxel N = 246 All Grades a % Grade 3 or 4 a % All Grades a % Grade 3 or 4 a % Hematology Decreased hemoglobin 79 14 83 16 Decreased white blood cell count 62 13 58 11 Decreased platelet count 48 4.1 48 7 Decreased lymphocytes 44 14 39 13 Decreased neutrophils 42 14 52 18 Chemistry Increased creatinine 75 1.7 82 0.4 Increased glucose 47 10 44 10 Increased AST 38 3.3 23 1.6 Increased ALT 30 2.5 19 0.8 Decreased albumin 29 0.8 21 0 Increased alkaline phosphatase 28 1.7 22 0.4 Increased amylase 21 5 11 1.6 Electrolytes Decreased magnesium 44 2.1 47 2 Decreased potassium 30 6 29 4.1 Decreased sodium 29 6 22 3.7 Decreased phosphate 21 1.2 18 3.7 Mismatch Repair Deficient Recurrent or Advanced Endometrial Cancer: JEMPERLI as a Single Agent The safety of JEMPERLI was evaluated in GARNET in 150 patients with advanced or recurrent dMMR EC who received at least 1 dose of JEMPERLI [see Clinical Studies ( 14.1 )] . Patients received JEMPERLI 500 mg every 3 weeks for 4 cycles followed by 1,000 mg every 6 weeks as an intravenous infusion until disease progression or unacceptable toxicity. Patients with autoimmune disease that required systemic therapy within 2 years of treatment or a medical condition that required immunosuppression were ineligible. Among patients receiving JEMPERLI, 41% were exposed for >1 year and 23% were exposed for >2 years. A fatal adverse reaction occurred in one patient (0.7%) who received JEMPERLI, due to concurrent immune-mediated encephalitis and urinary tract infection. Serious adverse reactions occurred in 38% of patients receiving JEMPERLI. Serious adverse reactions in >2% of patients included urinary tract infection (4%), sepsis (3.3%), acute kidney injury (2.7%), and abdominal pain (2.7%). JEMPERLI was permanently discontinued due to adverse reactions in 15 (10%) patients, including increased transaminases, sepsis, bronchitis, pneumonitis, rash, pruritus, pancreatitis, encephalitis, and nephritis. Dosage interruptions due to an adverse reaction occurred in 28% of patients who received JEMPERLI. Adverse reactions that required dosage interruption in >1% of patients who received JEMPERLI were anemia, diarrhea, asthenia, colitis, sepsis, and pneumonitis. The most common adverse reactions (≥20%) were fatigue/asthenia, anemia, nausea, diarrhea, constipation, vomiting, and rash. Table 5 summarizes the adverse reactions that occurred in ≥10% of patients with dMMR EC on JEMPERLI in GARNET. Table 5. Adverse Reactions (≥10%) in Patients with dMMR Endometrial Cancer Who Received JEMPERLI in GARNET dMMR = Mismatch Repair Deficient. Toxicity was graded per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03. a Includes fatigue and asthenia. b Includes anemia, decreased hemoglobin, iron deficiency, and iron deficiency anemia. c Includes rash, rash maculo-papular, rash pruritic, erythema, and pemphigoid. d Includes increased alanine aminotransferase, increased aspartate aminotransferase, increased transaminases, and hypertransaminasemia. Adverse Reaction JEMPERLI N = 150 All Grades % Grade 3 or 4 % General and administration site Fatigue a Pyrexia 49 13 3.3 0 Blood and lymphatic system Anemia b 35 18 Gastrointestinal Nausea 32 0.7 Diarrhea 29 2.7 Constipation 23 0.7 Vomiting 23 0.7 Skin and subcutaneous tissue Rash c Pruritus 21 19 0 1.3 Infections Urinary tract infection 19 4 Metabolism and nutrition Decreased appetite 15 0 Respiratory, thoracic, and mediastinal Cough 15 0 Musculoskeletal and connective tissue Myalgia 10 0 Investigations Increased transaminases d 13 4 Endocrine Disorders Hypothyroidism 11 0 Clinically relevant adverse reactions in <10% of patients who received JEMPERLI included: Endocrine Disorders: Hyperthyroidism, adrenal insufficiency, hypophysitis. Eye Disorders: Iridocyclitis, uveitis. Gastrointestinal Disorders: Colitis, pancreatitis, enterocolitis, gastritis. General Disorders and Administration Site Conditions: Chills. Musculoskeletal and Connective Tissue Disorders: Immune-mediated myositis, immune-mediated arthritis. Nervous System Disorders: Encephalitis. Renal and Urinary Disorders: Nephritis. Respiratory, Thoracic, and Mediastinal Disorders: Pneumonitis, interstitial lung disease. Table 6 summarizes laboratory abnormalities worsening from baseline to Grade 3 or 4 in ≥1% of patients with dMMR EC on JEMPERLI in GARNET. Table 6. Laboratory Abnormalities that Worsened from Baseline to Grade 3 or 4 Occurring in ≥1% of Patients with dMMR Endometrial Cancer Receiving JEMPERLI in GARNET dMMR = Mismatch Repair Deficient. a Consists of new onset of laboratory abnormality or worsening of baseline laboratory abnormality. Laboratory Test JEMPERLI N = 150 All Grades a % Grade 3 or 4 a % Hematology Decreased lymphocytes 46 15 Decreased leukocytes Decreased neutrophils 21 17 2 2.7 Chemistry Decreased albumin 36 2.7 Increased creatinine 33 3.4 Increased alkaline phosphatase 31 2.7 Increased aspartate aminotransferase 31 2 Increased alanine aminotransferase 25 4.7 Electrolytes Decreased sodium Decreased magnesium Decreased potassium 29 28 22 5 2 2 Increased calcium 8 2 Mismatch Repair Deficient Recurrent or Advanced Solid Tumors The 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 3 weeks for 4 cycles followed by 1,000 mg every 6 weeks as an intravenous infusion until disease progression or unacceptable toxicity. Patients with autoimmune disease that required systemic therapy within 2 years of treatment or a medical condition that required immunosuppression were ineligible. The median duration of exposure to JEMPERLI was 25 weeks (range: 1 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 1 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. Table 7 summarizes the adverse reactions that occurred in ≥10% of patients with dMMR recurrent or advanced solid tumors in GARNET. Table 7. Adverse Reactions (≥10%) in Patients with dMMR Recurrent or Advanced Solid Tumors in GARNET dMMR = Mismatch Repair Deficient. Toxicity was graded per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03. a Includes fatigue and asthenia. b Includes anemia, decreased hemoglobin, iron deficiency, and iron deficiency anemia. c 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 Reaction JEMPERLI N = 267 All Grades % Grade 3 or 4 % General and administration site Fatigue a 42 3.4 Pyrexia 12 0 Blood and lymphatic system Anemia b 30 11 Gastrointestinal Diarrhea 25 1.5 Nausea 22 0.4 Vomiting 17 1.5 Constipation 16 0.4 Skin and subcutaneous tissue Pruritus 15 0.4 Rash c 14 0.4 Respiratory, thoracic, and mediastinal Cough 13 0 Metabolism and nutrition Decreased appetite 12 0.4 Investigations Increased transaminases d 12 3 Clinically 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 8 summarizes laboratory abnormalities worsening from baseline to Grade 3 or 4 in ≥1% of patients with dMMR recurrent or advanced solid tumors in GARNET. Table 8. Laboratory Abnormalities that Worsened from Baseline to Grade 3 or 4 Occurring in ≥1% of Patients with dMMR Recurrent or Advanced Solid Tumors in GARNET dMMR = Mismatch Repair Deficient. a Consists of new onset of laboratory abnormality or worsening of baseline laboratory abnormality. Laboratory Test JEMPERLI N = 267 All Grades a % Grade 3 or 4 a % Hematology Decreased lymphocytes 33 7 Decreased leukocytes 18 1.1 Decreased neutrophils 12 1.5 Chemistry Decreased albumin 26 2.2 Increased alkaline phosphatase 26 3.4 Increased aspartate aminotransferase 26 1.5 Increased alanine aminotransferase 22 1.9 Increased creatinine 21 1.1 Increased total bilirubin 7 1.5 Electrolytes Decreased sodium 21 4.9 Decreased magnesium 16 1.1 Decreased potassium 14 1.1 Increased potassium 14 1.1 Increased calcium 6 1.1 Increased magnesium 4.1 1.5 Decreased calcium 2.6 1.5

12.3 Pharmacokinetics The pharmacokinetics of dostarlimab-gxly as a single agent and in combination with carboplatin and paclitaxel were evaluated in patients with various solid tumors, including patients with EC. Mean C max , AUC 0-inf , and AUC 0-tau increased proportionally over the dose range of 1 to 10 mg/kg. The Cycle 1 mean (coefficient of variation [%CV]) C max and AUC 0-tau of dostarlimab-gxly as a single agent were 171 mcg/mL (20%) and 35,730 mcg*h/mL (20%), respectively at the dosage of 500 mg once every 3 weeks and 309 mcg/mL (31%) and 95,820 mcg*h/mL (29%), respectively at the dosage of 1,000 mg every 6 weeks. Distribution The mean (%CV) volume of distribution of dostarlimab-gxly at steady state is approximately 5.8 L (15%). Elimination The mean terminal elimination half-life of dostarlimab-gxly at steady state is 23.5 days and its mean (%CV) clearance at steady state is 0.007 L/h (30%). Metabolism: Dostarlimab-gxly is expected to be metabolized into small peptides and amino acids by catabolic pathways. Specific Populations No clinically significant differences in the pharmacokinetics of dostarlimab-gxly were observed based on age (24 to 86 years), sex, race/ethnicity (75% White, 2% Asian, and 5% African American), tumor type, and renal impairment based on the estimated creatinine clearance (eGFR ≥15 mL/min/1.73 m 2 ), and mild to moderate hepatic impairment [total bilirubin (TB) >ULN to 3 times ULN or AST>ULN to any AST]. Drug Interaction Studies Dostarlimab exposure when administered in combination with carboplatin and paclitaxel was comparable to single agent exposure and there was no evidence to suggest a clinically relevant change of dostarlimab-gxly clearance over time in patients with recurrent or advanced EC.