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.
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.
gov/medwatch . 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.
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.
1% were exposed for >2 years. 3%). 4%). In patients receiving JEMPERLI in combination with carboplatin and paclitaxel, JEMPERLI was permanently discontinued due to adverse reactions in 46 patients (19%). 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. 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. 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. 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.
7%) who received JEMPERLI, due to concurrent immune-mediated encephalitis and urinary tract infection. Serious adverse reactions occurred in 38% of patients receiving JEMPERLI. 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. 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. 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. 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. 2%). Fatal adverse reaction occurred in 1 patient who received JEMPERLI due to respiratory failure. 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.
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. 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. 5