Jemperli Drug Information

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. • recurrent or advanced solid tumors. 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.

Recommended Dosage

The recommended dosage for JEMPERLI is presented in Table 1. Table 1. s 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.

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.

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.

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%).

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 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 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. Patients with autoimmune disease that required systemic therapy within 2 years of treatment or a medical condition that required immunosuppression were ineligible.

A fatal adverse reaction occurred in one patient (0.7%) who received JEMPERLI, due to concurrent immune-mediated encephalitis and urinary tract infection. JEMPERLI was permanently discontinued due to adverse reactions in 15 (10%) patients, including increased transaminases, sepsis, bronchitis, pneumonitis, rash, pruritus, pancreatitis, encephalitis, and nephritis. 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 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. Nervous System Disorders: Encephalitis. Renal and Urinary Disorders: Nephritis.

Respiratory, Thoracic, and Mediastinal Disorders: Pneumonitis, interstitial lung disease. 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 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.

The median duration of exposure to JEMPERLI was 25 weeks (range: 1 to 139 weeks). 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%).

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. 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 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.

Injury, Poisoning, and Procedural Complications: Infusion related reaction. Hepatobiliary Disorders: Hepatocellular injury. Musculoskeletal and Connective Tissue Disorders: Myalgia.

Table 8.

Pregnancy Risk Summary Based on its mechanism of action, JEMPERLI can cause fetal harm when administered to a pregnant woman. There are no available data on the use of JEMPERLI in pregnant women. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death (see ).

Human IgG4 immunoglobulins (IgG4) are known to cross the placental barrier; therefore, dostarlimab-gxly has the potential to be transmitted from the mother to the developing fetus. Advise women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 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.

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