Jemperli

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%) with JEMPERLI in combination with carboplatin and paclitaxel in patients with dMMR/MSI-H EC are rash, diarrhea, hypothyroidism, and hypertension. Most common Grade 3 or 4 laboratory abnormalities (≥10%) are decreased neutrophils, decreased hemoglobin, decreased white blood cell count, decreased lymphocytes, increased glucose, decreased sodium, and decreased platelets. ( 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 endometrial cancer (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 doses 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. Mismatch Repair Deficient (dMMR) or Microsatellite Instability-High (MSI-H) Primary Advanced or Recurrent EC: JEMPERLI in Combination with Carboplatin and Paclitaxel The safety of JEMPERLI in patients with primary advanced or recurrent dMMR/MSI-H EC was evaluated in RUBY [see Clinical Studies ( 14.1 )]. Patients received JEMPERLI 500 mg (n = 52) or placebo (n = 65) in combination with carboplatin and paclitaxel every 3 weeks for 6 doses followed by JEMPERLI 1,000 mg or placebo every 6 weeks until disease progression or unacceptable toxicity. Among the 52 patients, 56% were exposed for >1 year and 31% were exposed for >2 years. Serious adverse reactions occurred in 13% of patients receiving JEMPERLI in combination with carboplatin and paclitaxel; the most common serious adverse reaction was sepsis, including urosepsis (6%). Fatal adverse reactions occurred in 6% of patients receiving JEMPERLI including septic shock (3.8%), and myelosuppression (1.9%). In patients receiving JEMPERLI in combination with carboplatin and paclitaxel, JEMPERLI was permanently discontinued due to adverse reactions in 8 patients (15%) including 1 case (1.9%) each of rash maculo-papular, fatigue, general physical health deterioration, acute kidney injury, infusion-related reaction, keratitis, muscular weakness, and myelosuppression. Dosage interruptions due to an adverse reaction occurred in 35% 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, platelet count decreased, peripheral neuropathy, and rash. The most common adverse reactions, including laboratory abnormalities (≥20%), were decreased hemoglobin, decreased white blood cell count, decreased platelets, decreased lymphocytes, increased glucose, increased alkaline phosphatase, decreased neutrophils, rash, diarrhea, increased aspartate aminotransferase, increased alanine aminotransferase, decreased sodium, hypothyroidism, and hypertension. Table 3 summarizes the adverse reactions that occurred in ≥10% of patients with primary advanced or recurrent dMMR/MSI-H EC receiving JEMPERLI in combination with carboplatin and paclitaxel in RUBY. Table 3. Adverse Reactions (≥10%) in Patients with dMMR/MSI-H Endometrial Cancer Who Received JEMPERLI with Carboplatin and Paclitaxel in RUBY dMMR = Mismatch Repair Deficient; MSI-H = Microsatellite Instability-High. Graded per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03. a Includes rash, rash maculo-papular, palmar-plantar erythrodysesthesia syndrome, rash pustular, skin exfoliation, vulvovaginal rash, and dermatitis bullous. b Includes hypothyroidism and immune-mediated hypothyroidism. Adverse Reaction JEMPERLI with Carboplatin and Paclitaxel N = 52 Placebo with Carboplatin and Paclitaxel N = 65 All Grades % Grade 3 or 4 % All Grades % Grade 3 or 4 % Skin and subcutaneous tissue Rash a 42 8 20 0 Dry skin 12 0 8 0 Gastrointestinal disorders Diarrhea 40 1.9 31 0 Endocrine Disorders Hypothyroidism b 23 0 6 0 Vascular disorders Hypertension 21 10 11 6 General and administration site Pyrexia 14 0 1.5 0 Clinically relevant adverse reactions in <10% of patients with primary advanced or recurrent dMMR/MSI-H EC who received JEMPERLI in combination with carboplatin and paclitaxel included: Endocrine Disorders: Hyperthyroidism, thyroiditis. Eye Disorders: Keratitis. Gastrointestinal Disorders: Colitis, pancreatitis. Metabolism and Nutrition Disorders: Type 1 diabetes mellitus. Nervous System Disorders: Encephalopathy. Table 4 summarizes the laboratory abnormalities in patients with primary advanced or recurrent dMMR/MSI-H EC receiving JEMPERLI in combination with carboplatin and paclitaxel in RUBY. Table 4. Laboratory Abnormalities that Worsened from Baseline to Grade 3 or 4 Occurring in ≥10% of Patients with dMMR/MSI-H Endometrial Cancer Receiving JEMPERLI with Carboplatin and Paclitaxel in RUBY dMMR = Mismatch Repair Deficient; MSI-H = Microsatellite Instability-High. a Consists of new onset of laboratory abnormality or worsening of baseline laboratory abnormality. b Increased alkaline phosphatase, increased aspartate aminotransferase and increased alanine aminotransferase worsened from baseline to Grade 3 or 4 in <10% of patients. Laboratory Test JEMPERLI with Carboplatin and Paclitaxel N = 52 Placebo with Carboplatin and Paclitaxel N = 65 All Grades a % Grade 3 or 4 a % All Grades a % Grade 3 or 4 a % Hematology Decreased hemoglobin 77 17 86 25 Decreased platelets 54 10 57 12 Decreased lymphocytes 52 13 51 25 Decreased neutrophils 46 21 58 23 Decreased white blood cell count 73 15 68 14 Chemistry Increased glucose 50 13 54 11 Increased alkaline phosphatase b 48 6 26 0 Increased aspartate aminotransferase b 40 8 25 0 Increased alanine aminotransferase b 40 4 26 0 Electrolytes Decreased sodium 29 12 26 5 dMMR Recurrent or Advanced EC: 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 doses 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 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 dMMR 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 doses 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

4 CONTRAINDICATIONS None. None. ( 4 )

11 DESCRIPTION Dostarlimab-gxly is a programmed death receptor-1 (PD-1)–blocking IgG 4 humanized monoclonal antibody. Dostarlimab‑gxly is produced in Chinese hamster ovary cells and has a calculated molecular weight of about 144 kDa. JEMPERLI (dostarlimab-gxly) injection is a sterile, clear to slightly opalescent, colorless to yellow solution essentially free from visible particles. It is supplied as single-dose vials. Each vial contains 500 mg of JEMPERLI in 10 mL of solution with a pH of 6. Each mL of solution contains 50 mg of dostarlimab-gxly, citric acid monohydrate (0.48 mg), L-arginine hydrochloride (21.07 mg), polysorbate 80 (0.2 mg), sodium chloride (1.81 mg), trisodium citrate dihydrate (6.68 mg), and Water for Injection, USP.

2 DOSAGE AND ADMINISTRATION • JEMPERLI, in combination with carboplatin and paclitaxel, for dMMR or MSI-H primary advanced or recurrent endometrial cancer: 500 mg every 3 weeks for 6 doses followed by 1,000 mg monotherapy every 6 weeks. ( 2.2 ) • JEMPERLI, as a single agent, for dMMR recurrent or advanced endometrial cancer: 500 mg every 3 weeks for 4 doses followed by 1,000 mg every 6 weeks. ( 2.2 ) • JEMPERLI, as a single agent, for dMMR recurrent or advanced solid tumors: 500 mg every 3 weeks for 4 doses followed by 1,000 mg every 6 weeks. ( 2.2 ) • Administer as an intravenous infusion over 30 minutes. ( 2.2 ) • For complete dosing instructions, see full prescribing information. 2.1 Patient Selection Combination Therapy For use of JEMPERLI in combination with carboplatin and paclitaxel, select patients for treatment with JEMPERLI based on dMMR/MSI-H status in tumor specimens [see Clinical Studies ( 14.1 )]. 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 endometrial cancer [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 . • An FDA-approved test for the detection of MSI-H is not currently available [see Clinical Studies ( 14.1 )]. 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; MSI-H = Microsatellite Instability-High; EC = endometrial cancer. a First 6 doses are administered in combination with carboplatin and paclitaxel. Refer to the Prescribing Information for the agents administered in combination with JEMPERLI, as appropriate. b 30-minute intravenous infusion. Indication Recommended Dosage Duration/Timing of Treatment Combination Therapy Adults with dMMR/MSI-H primary advanced or recurrent EC 500 mg b every 3 weeks for 6 doses a followed by 1,000 mg b monotherapy every 6 weeks 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 b every 3 weeks for 4 doses followed by 1,000 mg b every 6 weeks 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 AST = 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. a Based on National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0. 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. • 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). JEMPERLI is compatible with an infusion bag made of polyolefin, ethylene vinyl acetate, or polyvinyl chloride with di(2-ethylhexyl) phthalate (DEHP). • 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.

1 INDICATIONS AND USAGE JEMPERLI is a programmed death receptor-1 (PD-1)–blocking antibody indicated: Endometrial Cancer (EC) • 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 that is mismatch repair deficient (dMMR), as determined by an FDA-approved test, or microsatellite instability-high (MSI-H). ( 1.1 , 2.1 ) • as a single agent for the treatment of adult patients with dMMR recurrent or advanced endometrial cancer, 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 , 2.1 ) 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 ) 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) that is mismatch repair deficient (dMMR), as determined by an FDA-approved test, or microsatellite instability-high (MSI-H) [see Dosage and Administration ( 2.1 )]. JEMPERLI, as a single agent, is indicated for the treatment of adult patients with dMMR recurrent or advanced endometrial cancer, 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).

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells inhibits T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors, and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Dostarlimab-gxly is a humanized monoclonal antibody of the IgG4 isotype that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth. 12.2 Pharmacodynamics The exposure-response relationship and time course of pharmacodynamic response for safety and effectiveness of dostarlimab-gxly have not been fully characterized. Dostarlimab-gxly provides sustained target engagement as measured by direct PD-1 binding and stimulation of IL-2 production throughout the dosing interval at the recommended dose. 12.3 Pharmacokinetics The pharmacokinetics of dostarlimab-gxly as a single agent and in combination with carboplatin and paclitaxel were evaluated using population PK analysis in patients with various solid tumors, including 546 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%) at the dosage of 500 mg once every 3 weeks and 309 mcg/mL (31%) and 95,820 mcg*h/mL (29%) at the dosage of 1,000 mg every 6 weeks, respectively. The exposures of dostarlimab-gxly administered in combination with carboplatin and paclitaxel and as a single agent were comparable. 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 is 0.007 L/h (30%) at steady state. 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 and mild [total bilirubin (TB) > ULN to 1.5 times ULN or aspartate aminotransferase (AST) > ULN] to moderate (TB > 1.5 to 3 times ULN and any AST) hepatic impairment. 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 endometrial cancer. 12.6 Immunogenicity The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of JEMPERLI or of other dostarlimab-gxly products. The immunogenicity of dostarlimab-gxly was evaluated in RUBY at a dose of 500 mg every 3 weeks for 6 doses followed by 1,000 mg every 6 weeks thereafter; there was no formation of treatment-emergent anti-drug antibodies and treatment-emergent neutralizing antibodies in 225 patients receiving JEMPERLI at the recommended dosage. The immunogenicity of dostarlimab-gxly was evaluated in GARNET at a dose of 500 mg every 3 weeks for 4 doses followed by 1,000 mg every 6 weeks thereafter. Treatment‑emergent anti‑drug antibodies against dostarlimab-gxly were detected in 2.1% (8/384) of patients who received JEMPERLI at the recommended dosage. Neutralizing antibodies were detected in 1% (4/384) 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.

12.1 Mechanism of Action Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells inhibits T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors, and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Dostarlimab-gxly is a humanized monoclonal antibody of the IgG4 isotype that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth.

12.2 Pharmacodynamics The exposure-response relationship and time course of pharmacodynamic response for safety and effectiveness of dostarlimab-gxly have not been fully characterized. Dostarlimab-gxly provides sustained target engagement as measured by direct PD-1 binding and stimulation of IL-2 production throughout the dosing interval at the recommended dose.

12.3 Pharmacokinetics The pharmacokinetics of dostarlimab-gxly as a single agent and in combination with carboplatin and paclitaxel were evaluated using population PK analysis in patients with various solid tumors, including 546 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%) at the dosage of 500 mg once every 3 weeks and 309 mcg/mL (31%) and 95,820 mcg*h/mL (29%) at the dosage of 1,000 mg every 6 weeks, respectively. The exposures of dostarlimab-gxly administered in combination with carboplatin and paclitaxel and as a single agent were comparable. 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 is 0.007 L/h (30%) at steady state. 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 and mild [total bilirubin (TB) > ULN to 1.5 times ULN or aspartate aminotransferase (AST) > ULN] to moderate (TB > 1.5 to 3 times ULN and any AST) hepatic impairment. 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 endometrial cancer.

20230731

8

3 DOSAGE FORMS AND STRENGTHS 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. Injection: 500 mg/10 mL (50 mg/mL) solution in a single-dose vial. ( 3 )

Jemperli dostarlimab DOSTARLIMAB DOSTARLIMAB CITRIC ACID MONOHYDRATE ARGININE HYDROCHLORIDE POLYSORBATE 80 SODIUM CHLORIDE TRISODIUM CITRATE DIHYDRATE WATER

13.2 Animal Toxicology and/or Pharmacology In animal models, inhibition of PD-L1/PD-1 signaling increased the severity of some infections and enhanced inflammatory responses. Mycobacterium tuberculosis -infected PD-1 knockout mice exhibit markedly decreased survival compared with wild-type controls, which correlated with increased bacterial proliferation and inflammatory responses in these animals. PD-1 blockade using a primate anti-PD-1 antibody was also shown to exacerbate M. tuberculosis infection in rhesus macaques. PD-L1 and PD-1 knockout mice and mice receiving PD-L1–blocking antibody have also shown decreased survival following infection with lymphocytic choriomeningitis virus.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No studies have been performed to assess the potential of dostarlimab-gxly for carcinogenicity or genotoxicity. Fertility studies have not been conducted with dostarlimab-gxly. In 1- and 3-month repeat‑dose toxicology studies in monkeys, there were no notable effects in the male and female reproductive organs; however, many animals in these studies were not sexually mature.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No studies have been performed to assess the potential of dostarlimab-gxly for carcinogenicity or genotoxicity. Fertility studies have not been conducted with dostarlimab-gxly. In 1- and 3-month repeat‑dose toxicology studies in monkeys, there were no notable effects in the male and female reproductive organs; however, many animals in these studies were not sexually mature. 13.2 Animal Toxicology and/or Pharmacology In animal models, inhibition of PD-L1/PD-1 signaling increased the severity of some infections and enhanced inflammatory responses. Mycobacterium tuberculosis -infected PD-1 knockout mice exhibit markedly decreased survival compared with wild-type controls, which correlated with increased bacterial proliferation and inflammatory responses in these animals. PD-1 blockade using a primate anti-PD-1 antibody was also shown to exacerbate M. tuberculosis infection in rhesus macaques. PD-L1 and PD-1 knockout mice and mice receiving PD-L1–blocking antibody have also shown decreased survival following infection with lymphocytic choriomeningitis virus.

BLA761174

Jemperli

dostarlimab

0173-0898

HUMAN PRESCRIPTION DRUG

INTRAVENOUS

PRINCIPAL DISPLAY PANEL NDC 0173-0898-03 Jemperli (dostarlimab-gxly) Injection 500 mg/10 mL (50 mg/mL) gsk For Intravenous Infusion after Dilution Single-Dose Vial Rx only Dispense the enclosed Medication Guide to each patient ©2020 GSK group of companies or its licensor. Rev. 3/23 PCR-0022923 Jemperli 10 mL carton

Indications and Usage ( 1 ) 7/2023 Dosage and Administration ( 2.1 , 2.2 ) 7/2023 Warnings and Precautions, Severe and Fatal Immune-Mediated Adverse Reactions ( 5.1 ) 7/2023

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Immune-Mediated Adverse Reactions Inform 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: • Pneumonitis: 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 )] . • Colitis: Advise patients to contact their healthcare provider immediately for diarrhea or severe abdominal pain [see Warnings and Precautions ( 5.1 )] . • Hepatitis: 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 )] . • Immune-mediated endocrinopathies: Advise patients to contact their healthcare provider immediately for signs or symptoms of hypothyroidism, hyperthyroidism, thyroiditis, adrenal insufficiency, hypophysitis, or type 1 diabetes mellitus [see Warnings and Precautions ( 5.1 )] . • Nephritis: Advise patients to contact their healthcare provider immediately for signs or symptoms of nephritis [see Warnings and Precautions ( 5.1 )] . • Severe 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 )] . • Other immune-mediated adverse reactions: • Advise 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 )] . • Advise 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 Reactions • Advise 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 • Advise patients of the risk of post-allogeneic hematopoietic stem cell transplantation complications [see Warnings and Precautions ( 5.3 )] . Embryo-Fetal Toxicity • Advise females of reproductive potential of the potential risk to a fetus and to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions ( 5.4 ), Use in Specific Populations ( 8.1 , 8.3 )]. • Advise females of reproductive potential to use effective contraception during treatment with JEMPERLI and for 4 months after the last dose [see Warnings and Precautions ( 5.4 ), Use in Specific Populations ( 8.1 , 8.3 )]. Lactation • Advise women not to breastfeed during treatment with JEMPERLI and for 4 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 by GlaxoSmithKline LLC Philadelphia, PA 19104 U.S. License No. 1727 Distributed by GlaxoSmithKline Durham, NC 27701 ©2023 GSK group of companies or its licensor. JMP:5PI

MEDICATION GUIDE JEMPERLI (jem-PER-lee) (dostarlimab-gxly) injection What is the most important information I should know about JEMPERLI? JEMPERLI is a 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. • cough • shortness of breath • chest pain Intestinal problems. • diarrhea or more bowel movements than usual • stools that are black, tarry, sticky, or have blood or mucus • severe stomach-area (abdomen) pain or tenderness Liver problems. • yellowing of your skin or the whites of your eyes • severe nausea or vomiting • pain on the right side of your stomach area (abdomen) • dark urine (tea colored) • bleeding or bruising more easily than usual Hormone gland problems. • headaches that will not go away or unusual headaches • eye sensitivity to light • eye problems • rapid heartbeat • increased sweating • extreme tiredness • weight gain or weight loss • feeling more hungry or thirsty than usual • urinating more often than usual • hair loss • feeling cold • constipation • your voice gets deeper • dizziness or fainting • changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness Kidney problems. • change in the amount or color of your urine • blood in your urine • swelling in your ankles • loss of appetite Skin problems. • rash • itching • skin blistering or peeling • swollen lymph nodes • painful sores or ulcers in your mouth or in your nose, throat, or genital area • fever or flu-like symptoms Problems 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. • chest pain, irregular heartbeat, shortness of breath, swelling of ankles • confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs • double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight • persistent or severe muscle pain or weakness, muscle cramps • low red blood cells, bruising Infusion reactions that can sometimes be severe or life-threatening. Signs and symptoms of infusion reactions may include: • chills or shaking • itching or rash • flushing • shortness of breath or wheezing • dizziness • feel like passing out • fever • back or neck pain Rejection of a 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 a 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 JEMPERLI? JEMPERLI is a prescription medicine used to treat adults with: • a kind of uterine cancer called endometrial cancer (EC) • JEMPERLI may be used in combination with the chemotherapy medicines carboplatin and paclitaxel, and then after that JEMPERLI may be used alone: • when a laboratory test shows that your tumor is mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H), and • your cancer has spread outside your uterus (advanced) or , • your cancer has returned. • JEMPERLI may be used alone: • when a laboratory test shows that your tumor is mismatch repair deficient (dMMR), and • your cancer has returned, or it has spread (advanced EC), and • you have received chemotherapy that contains platinum and it did not work or is no longer working, and • your cancer cannot be treated by surgery or radiation. • a kind of cancer that is shown by laboratory test to be mismatch repair deficient (dMMR) solid tumor. JEMPERLI may be used to treat: • cancer that has returned or has spread (advanced cancer) and , • has 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 receiving JEMPERLI, tell your healthcare provider about all of your medical conditions, including if you: • have immune system problems, such as Crohn’s disease, ulcerative colitis, or lupus. • have received an organ transplant. • have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic). • have received radiation treatment to your chest area. • have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome. • are pregnant or plan to become pregnant. JEMPERLI can harm your unborn baby. Females who are able to become pregnant: 1. Your healthcare provider will do a pregnancy test before you start treatment with JEMPERLI. 2. You should use an effective method of birth control during your treatment and for 4 months after your last dose of JEMPERLI. Talk to your healthcare provider about birth control methods that you can use during this time. 3. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with JEMPERLI. • are breastfeeding or plan to breastfeed. It is not known if JEMPERLI passes into your breast milk. Do not breastfeed during treatment and for 4 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 I receive JEMPERLI? • Your healthcare provider will give you JEMPERLI into your vein through an intravenous (IV) line over 30 minutes. • When JEMPERLI is used in combination with carboplatin and paclitaxel, JEMPERLI is usually given every 3 weeks for the first 6 doses. Beginning 3 weeks later, it is usually given alone every 6 weeks. • When JEMPERLI is used alone to treat dMMR recurrent or advanced EC and dMMR recurrent or advanced solid tumors, it is usually given every 3 weeks for the first 4 doses. Beginning 3 weeks later, it is usually given every 6 weeks. • Your healthcare provider will decide how many treatments you need. • Your healthcare provider will do blood tests to check you for side effects. • If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment. What are the possible side effects of JEMPERLI? JEMPERLI can cause serious side effects. • See “What is the most important information I should know about JEMPERLI?” The most common side effects of JEMPERLI when given with carboplatin and paclitaxel in people with dMMR/MSI-H endometrial cancer include: • rash • diarrhea • decreased thyroid function • high blood pressure The most common side effects of JEMPERLI in people with dMMR solid tumors (including endometrial cancer) when used alone include: • tiredness and weakness • low red blood cell count (anemia) • diarrhea • nausea • constipation • vomiting These are not all of 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 a 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 JEMPERLI? Active ingredient: dostarlimab-gxly Inactive 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 19104, U.S. License No. 1727 Distributed by: GlaxoSmithKline, Durham, NC 27701 ©2023 GSK group of companies or its licensor. JMP:4MG This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: July 2023

14 CLINICAL STUDIES 14.1 Endometrial Cancer In Combination with Carboplatin and Paclitaxel for the Treatment of dMMR or MSI-H Primary Advanced or Recurrent Endometrial Cancer The efficacy of JEMPERLI in combination with carboplatin and paclitaxel, followed by JEMPERLI as a single agent, was evaluated in RUBY (NCT03981796), a randomized, multicenter, double-blind, placebo-controlled trial. Efficacy was assessed in a pre-specified subgroup of 122 patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer. The identification of dMMR/MSI-H tumor status was prospectively determined based on local testing assays (IHC, PCR or NGS), or central testing (IHC) using the VENTANA MMR RxDx Panel when no local result was available. The trial enrolled patients with primary Stage III or Stage IV disease (per FIGO Staging Classification), including Stage IIIA to IIIC1 patients with evaluable or measurable disease, Stage IIIC1 patients with carcinosarcoma, clear cell, serous, or mixed histology regardless of presence of measurable disease, Stage IIIC2 or Stage IV disease regardless of presence of measurable disease. The trial also enrolled patients with first recurrent disease with a low potential for cure by radiation therapy or surgery alone or in combination, including patients who were naïve to systemic anticancer therapy or who had received prior neo-adjuvant/adjuvant systemic anticancer therapy and had a recurrence or disease progression ≥6 months after completing treatment. Patients were randomized (1:1) to one of the following treatments arms: • JEMPERLI 500 mg, carboplatin AUC 5 mg/mL/min, paclitaxel 175 mg/m 2 intravenously on Day 1 of each 21-day cycle for 6 doses followed by JEMPERLI 1,000 mg intravenously every 6 weeks. JEMPERLI was administered prior to chemotherapy on Day 1. • Placebo, carboplatin AUC 5 mg/mL/min, paclitaxel 175 mg/m 2 intravenously on Day 1 of each 21-day cycle for 6 doses followed by placebo intravenously every 6 weeks. Randomization was stratified by MMR/MSI status, prior external pelvic radiotherapy, and disease status (recurrent, primary Stage III, or primary Stage IV). Treatment with JEMPERLI continued until disease progression, unacceptable toxicity, or a maximum of 3 years. Administration of JEMPERLI was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered to be deriving clinical benefit by the investigator. Assessment of tumor status was performed every 6 weeks through Week 25, every 9 weeks through Week 52 and every 12 weeks thereafter. In the dMMR/MSI-H subgroup, the major efficacy outcome was investigator-assessed progression-free survival (PFS) using Response Evaluation Criteria in Solid Tumors (RECIST v 1.1). Additional efficacy outcome measures included overall survival (OS), Objective Response Rate (ORR), and Duration of Response (DOR). The major efficacy outcomes for the overall population were investigator-assessed PFS using RECIST v 1.1 and OS, with additional efficacy outcome measures of ORR and DOR. Among the 122 patients evaluated, the baseline characteristics were: median age 65 years (50% aged 65 years or older); 83% White, 9% Black, 3% Asian; Eastern Cooperative Oncology Group (ECOG) Performance Status 0 (57%) or 1 (43%); and primary stage III (22%); primary stage IV (28%) and recurrent EC (50%). Efficacy results are presented in Table 9 and Figure 1 . Overall survival data in this subpopulation were immature with 27% deaths. Table 9. Efficacy Results of dMMR/MSI-H Endometrial Cancer Population in RUBY dMMR = Mismatch Repair Deficient; MSI-H = Microsatellite Instability-High; NR = Not Reached; + = ongoing at last assessment. a One-sided p-value based on stratified log-rank test was statistically significant. b Based on stratified Cox regression model. c Confirmed responses as assessed by investigator according to RECIST v1.1. d For patients with a partial or complete response. Endpoint JEMPERLI with Carboplatin and Paclitaxel N = 60 Placebo withCarboplatin and Paclitaxel N = 62 Progression-Free Survival (PFS) Number (%) of patients with event 23 (38.3) 47 (75.8) Median in months (95% CI) a 30.3 (11.8, NR) 7.7 (5.6, 9.7) Hazard ratio (95% CI) b 0.29 (0.17, 0.50) p - value a <0.0001 Objective Response Rate (ORR) c Number of participants with measurable disease at baseline (n) 42 45 ORR, n (%) (95% CI) 31 (73.8) (58.0, 86.1) 28 (62.2) (46.5, 76.2) Complete response rate, n (%) 11 (26.2) 5 (11.1) Partial response rate, n (%) 20 (47.6) 23 (51.1) Duration of Response (DOR) c, d Number of Responders 31 28 Median in months (range) NR (3.4, 28.3+) 5.4 (2.7, 27.2+) Patients with duration >12 months, n (%) 19 (61.3) 4 (14.3) Figure 1. Kaplan-Meier Curve for Progression-free Survival in patients with dMMR/MSI-H Endometrial Cancer in RUBY As a Single Agent for the Treatment of dMMR Recurrent or Advanced Endometrial Cancer The efficacy of JEMPERLI as a single agent was evaluated in the GARNET trial (NCT02715284), a multicenter, multicohort, open-label trial conducted in patients with advanced solid tumors. The efficacy population consisted of a cohort of 141 patients with dMMR recurrent or advanced EC who had progressed on or after treatment with a 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 2 years were excluded from the trial. Patients received JEMPERLI 500 mg intravenously every 3 weeks for 4 doses followed by 1,000 mg intravenously every 6 weeks. Treatment continued until disease progression or unacceptable toxicity. The major efficacy outcome measures were ORR and DOR as assessed by BICR according to the RECIST v 1.1. The baseline characteristics were: median age 65 years (53% aged 65 years or older); 77% White, 4% Asian, 3% Black, 4% Hispanic or Latino; and Eastern Cooperative Oncology Group Performance Status 0 (38%) or 1 (62%). The most common histology seen was endometrioid carcinoma type 1 (65%), Grade 3 endometrioid (15%), followed by serous (5%), mixed (5%) and undifferentiated (2.8%). All patients with dMMR EC had received prior anticancer treatment, with 89% of patients receiving prior anticancer surgery and 71% receiving prior anticancer radiotherapy. Sixty-three percent of patients had one prior line of anticancer treatment and 37% had two or more prior lines. Forty-eight patients (34%) received treatment only in the neoadjuvant or adjuvant setting before participating in the study. The dMMR tumor status was retrospectively confirmed using the VENTANA MMR RxDx Panel assay. Efficacy results are presented in Table 10 . Table 10. Efficacy Results of dMMR Endometrial Cancer Population in GARNET dMMR = Mismatch Repair Deficient; + = ongoing at last assessment. a Based on confirmed response by blinded independent central review. b Median follow up for duration of response was 27.9 months measured from time of first response. Endpoint JEMPERLI N = 141 Overall response rate a ORR (95% CI) 45.4% (37.0, 54.0) Complete response rate 15.6% Partial response rate 29.8% Duration of response b Median in months Not reached (range) (1.2+, 52.8+) Patients with duration ≥12 months 85.9% Patients with duration >24 months 54.7% Figure 1 14.2 Mismatch Repair Deficient Recurrent or Advanced Solid Tumors The efficacy of JEMPERLI as a single agent was evaluated in GARNET (NCT02715284), a non‑randomized, multicenter, open-label, multicohort trial. The efficacy population consisted of a 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 a platinum-containing regimen. Patients with dMMR colorectal cancer must have progressed after or been intolerant to a 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 2 years were excluded from the trial. Patients received JEMPERLI 500 mg intravenously every 3 weeks for 4 doses followed by 1,000 mg intravenously every 6 weeks. Treatment continued until disease progression or unacceptable toxicity. The major efficacy outcome measures were ORR and DOR as determined by a BICR according to RECIST v 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 0 (39%) or 1 (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 1 prior line of systemic anticancer treatment, 36% had received 2 prior lines, and 21% had received 3 or more prior lines. The dMMR tumor status was retrospectively confirmed using the VENTANA MMR RxDx Panel assay. Efficacy results are presented in Tables 11 and 12 . Table 11. Efficacy Results of dMMR Recurrent or Advanced Solid Tumors in GARNET dMMR = Mismatch Repair Deficient; + = ongoing at last assessment. a Based on confirmed response by blinded independent central review. b Median follow-up for duration of response was 17.5 months measured from time of first response. Endpoint JEMPERLI N = 209 Overall response rate a ORR (95% CI) 41.6% (34.9, 48.6) Complete response rate 9.1% Partial response rate 32.5% Duration of response b Median in months 34.7 (range) 2.6, 35.8+ Patients with duration ≥6 months 95.4% Table 12. Efficacy Results of dMMR Tumor Types in GARNET dMMR = Mismatch Repair Deficient; ORR = Overall Response Rate; DOR = Duration of Response; EC = endometrial cancer; CRC = colorectal cancer; PR = partial response; PD = progressive disease; CR = complete response; SD = stable disease; + = ongoing at last assessment. a Exact, 2-sided 95% CI for binomial proportion. Tumor Type Patients N ORR (per RECIST v 1.1) DOR n (%) 95% CI a Range (months) EC 103 46 (44.7) (34.9, 54.8) 2.6, 35.8+ non-EC 106 41 (38.7) (29.4, 48.6) 5.6, 30.1+ CRC 69 25 (36.2) (25.0, 48.7) 5.6, 30.1+ Small intestinal cancer 12 4 (33.3) (9.9, 65.1) 11.1+, 28.0+ Gastric cancers 8 3 (37.5) (8.5, 75.5) 8.4+, 17.5 Pancreatic carcinoma 4 0 (0.0) (0.0, 60.2) NA Biliary neoplasm 2 CR, CR NA 8.4+, 13.5+ Liver cancer 2 PR, PD NA 13.8+ Ovarian cancer 2 PR, SD NA 25.1+ Adrenal cortical 1 PR NA 19.5+ Breast cancer 1 CR NA 16.8+ Esophageal cancer 1 PD NA NA Genital neoplasm malignant female 1 PR NA 22.2+ Pleural 1 PR NA 15.2+ Renal cell carcinoma 1 SD NA NA Unknown origin 1 PR NA 20.4+

8.5 Geriatric Use In Combination with Carboplatin and Paclitaxel Of the 241 patients treated with JEMPERLI in RUBY, 52.3% were younger than 65 years, 36.5% were aged 65 through 75 years, and 11.2% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients. As a Single Agent Of the 605 patients treated with JEMPERLI in GARNET, 51.6% were younger than 65 years, 36.9% were aged 65 through 75 years, and 11.5% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.

8.4 Pediatric Use The safety and efficacy of JEMPERLI have not been established in pediatric patients.

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 ( 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 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 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 ) 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 ( 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 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. 8.2 Lactation Risk Summary There is no information regarding the presence of dostarlimab-gxly in human milk or its effects on the breastfed child or on milk production. Maternal IgG is known to be present in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to JEMPERLI are unknown. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment and for 4 months after the last dose of JEMPERLI. 8.3 Females and Males of Reproductive Potential JEMPERLI can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )] . Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating JEMPERLI [see Use in Specific Populations ( 8.1 )]. Contraception Females: Advise females of reproductive potential to use effective contraception during treatment with JEMPERLI and for 4 months after the last dose. 8.4 Pediatric Use The safety and efficacy of JEMPERLI have not been established in pediatric patients. 8.5 Geriatric Use In Combination with Carboplatin and Paclitaxel Of the 241 patients treated with JEMPERLI in RUBY, 52.3% were younger than 65 years, 36.5% were aged 65 through 75 years, and 11.2% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients. As a Single Agent Of the 605 patients treated with JEMPERLI in GARNET, 51.6% were younger than 65 years, 36.9% were aged 65 through 75 years, and 11.5% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.

16 HOW SUPPLIED/STORAGE AND HANDLING JEMPERLI (dostarlimab-gxly) injection is a clear to slightly opalescent, colorless to yellow solution supplied in a carton containing one 500 mg/10 mL (50 mg/mL), single-dose vial (NDC 0173-0898-03). Store vial refrigerated at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze or shake.