5) ] RYBREVANT in Combination with Lazertinib The most common adverse reactions (≥ 20%) were rash, nail toxicity, infusion-related reaction, musculoskeletal pain, stomatitis, edema, VTE, paresthesia, fatigue, diarrhea, constipation, COVID-19, hemorrhage, dry skin, decreased appetite, pruritus, and nausea.
1 ) The most common Grade 3 or 4 laboratory abnormalities (≥ 2%) were decreased albumin, decreased sodium, increased ALT, decreased potassium, decreased hemoglobin, increased AST, increased GGT, and increased magnesium. 1 ) RYBREVANT in Combination with Carboplatin and Pemetrexed The most common adverse reactions (≥ 20%) were rash, nail toxicity, infusion-related reaction, fatigue, nausea, stomatitis, constipation, edema, decreased appetite, musculoskeletal pain, vomiting, and COVID-19.
1 ) The most common Grade 3 or 4 laboratory abnormalities (≥ 2%) were decreased neutrophils, decreased leukocytes, decreased platelets, decreased hemoglobin, decreased potassium, decreased sodium, increased alanine aminotransferase, increased gamma glutamyl transferase, and decreased albumin.
1 ) RYBREVANT as a Single Agent The most common adverse reactions (≥ 20%) were rash, IRR, paronychia, musculoskeletal pain, dyspnea, nausea, fatigue, edema, stomatitis, cough, constipation, and vomiting. 1 ) The most common Grade 3 or 4 laboratory abnormalities (≥ 2%) were decreased lymphocytes, decreased albumin, decreased phosphate, decreased potassium, increased alkaline phosphatase, increased glucose, increased gamma-glutamyl transferase, and decreased sodium.
1 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Biotech, Inc. 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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
1) ] . Patients received RYBREVANT intravenously at 1,050 mg (for patients < 80 kg) or 1,400 mg (for patients ≥ 80 kg) once weekly for 4 weeks, then every 2 weeks thereafter starting at week 5 in combination with lazertinib, 240 mg orally once daily, until disease progression or unacceptable toxicity.
Among 421 patients who received RYBREVANT in combination with lazertinib, 73% were exposed for 6 months or longer and 59% were exposed for greater than one year. The most common adverse reactions (≥ 20%) were rash, nail toxicity, infusion-related reaction, edema, musculoskeletal pain, stomatitis, VTE, paresthesia, fatigue, diarrhea, constipation, COVID-19, dry skin, hemorrhage, decreased appetite, pruritus, and nausea.
The most common Grade 3 or 4 laboratory abnormalities (≥ 2%) were decreased albumin, increased ALT, decreased sodium, decreased hemoglobin, increased AST, increased GGT and increased magnesium. 2) ] in 130 patients with previously treated locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations whose disease has progressed on or after treatment with osimertinib.
3) ] in 151 patients with previously untreated, locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. Patients received RYBREVANT intravenously at 1,400 mg (for patients < 80 kg) or 1,750 mg (for patients ≥ 80 kg) once weekly through 4 weeks, then every 3 weeks with a dose of 1,750 mg (for patients < 80 kg) or 2,100 mg (for patients ≥ 80 kg) starting at Week 7 until disease progression or unacceptable toxicity, in combination with carboplatin at area under the curve AUC 5 once every 3 weeks, for up to 12 weeks, and pemetrexed at 500 mg/m 2 once every 3 weeks until disease progression or unacceptable toxicity.
Among 281 patients who received RYBREVANT in combination with carboplatin and pemetrexed, 65% were exposed for 6 months or longer and 24% were exposed for greater than one year. In the safety population, the most common (≥ 20%) adverse reactions were rash, nail toxicity, infusion-related reaction, fatigue, nausea, stomatitis, constipation, edema, decreased appetite, musculoskeletal pain, vomiting, and COVID-19.
The most common Grade 3 to 4 laboratory abnormalities (≥ 2%) were decreased neutrophils, decreased leukocytes, decreased platelets, decreased hemoglobin, decreased potassium, decreased sodium, increased alanine aminotransferase, increased gamma-glutamyl transferase, and decreased albumin.
4) ] in 302 patients with locally advanced or metastatic NSCLC. Patients received RYBREVANT at 1,050 mg (for patient baseline body weight < 80 kg) or 1,400 mg (for patient baseline body weight ≥ 80 kg) once weekly for 4 weeks, then every 2 weeks thereafter until disease progression or unacceptable toxicity.
Among 302 patients who received RYBREVANT as a single agent, 36% were exposed for 6 months or longer and 12% were exposed for greater than one year. In the safety population, the most common (≥ 20%) adverse reactions were rash, infusion-related reaction, paronychia, musculoskeletal pain, dyspnea, nausea, edema, cough, fatigue, stomatitis, constipation, vomiting and pruritus.
The most common Grade 3 to 4 laboratory abnormalities (≥ 2%) were increased gamma glutamyl transference, decreased sodium, decreased potassium and increased alkaline phosphatase. 1) ]. Patients received RYBREVANT intravenously at 1,050 mg (for patients < 80 kg) or 1,400 mg (for patients ≥ 80 kg) once weekly for 4 weeks, then every 2 weeks thereafter starting at week 5 in combination with lazertinib, 240 mg orally once daily.
Among the 421 patients who received RYBREVANT in combination with lazertinib, 73% were exposed to RYBREVANT for ≥ 6 months and 59% were exposed to RYBREVANT for > 1 year. 7% were Black or African American, 1% were of unknown or other races; and 13% were Hispanic or Latino, 67% had Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1, 33% had ECOG PS of 0, 60% had EGFR exon 19 deletions, and 40% had EGFR exon 21 L858R substitution mutations.
Serious adverse reactions occurred in 49% of patients who received RYBREVANT in combination with lazertinib. 1% each). 2% each). Permanent discontinuation of RYBREVANT due to an adverse reaction occurred in 34% of patients. Adverse reactions which resulted in permanent discontinuation in ≥ 1% of patients included rash, infusion-related reactions, nail toxicity, VTE, ILD/pneumonitis, pneumonia, edema, hypoalbuminemia, fatigue, paresthesia and dyspnea.
Dosage interruption of RYBREVANT due to an adverse reaction occurred in 88% of patients. Adverse reactions which required dosage interruption in ≥ 5% of patients were infusion-related reactions, rash, nail toxicity, COVID-19, VTE, increased ALT, edema, and hypoalbuminemia.
Dose reductions of RYBREVANT due to an adverse reaction occurred in 46% of patients. Adverse reactions requiring dose reductions in ≥ 5% of patients were rash and nail toxicity. The most common adverse reactions (≥ 20%) were rash, nail toxicity, infusion-related reaction, musculoskeletal pain, stomatitis, edema, VTE, paresthesia, fatigue, diarrhea, constipation, COVID-19, hemorrhage, dry skin, decreased appetite, pruritus, and nausea.
The most common Grade 3 or 4 laboratory abnormalities (≥ 2%) were decreased albumin, decreased sodium, increased ALT, decreased potassium, decreased hemoglobin, increased AST, increased GGT, and increased magnesium. Table 10 summarizes the adverse reactions (≥ 10%) in MARIPOSA.
7 7 0 Psychiatric disorders Insomnia 10 0 11 0 Clinically relevant adverse reactions in < 10% of patients who received RYBREVANT in combination with lazertinib included skin ulcer and ILD/pneumonitis. Table 11 summarizes the laboratory abnormalities in MARIPOSA.
Table 11:
Select Laboratory Abnormalities (≥ 20%) That Worsened from Baseline in Patients with NSCLC with EGFR Exon 19 Deletion or Exon 21 L858R Substitution Mutations in MARIPOSA The denominator used to calculate the rate is the number of patients with a baseline value and at least one post-treatment value for the specific lab test.
2) ]. Eligible patients had locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations with progressive disease on or after treatment with osimertinib . Patients with asymptomatic or previously treated and stable intracranial metastases were eligible.
Patients received RYBREVANT intravenously at 1,400 mg (for patients < 80 kg) or 1,750 mg (for patients ≥ 80 kg) once weekly through 4 weeks, then every 3 weeks with a dose of 1,750 mg (for patients < 80 kg) or 2,100 mg (for patients ≥ 80 kg) starting at Week 7 until disease progression or unacceptable toxicity, in combination with carboplatin at area under the curve AUC 5 once every 3 weeks, for up to 12 weeks, and pemetrexed at 500 mg/m 2 once every 3 weeks until disease progression or unacceptable toxicity.
Among patients who received RYBREVANT (n=130), 52% were exposed for 6 months or longer and 7% were exposed for greater than one year. 7 months). 8% Alaska native; 7% were Hispanic or Latino; and 87% had baseline body weight < 80 kg. Serious adverse reactions occurred in 32% of patients who received RYBREVANT in combination with carboplatin and pemetrexed.
3%). 8% each). Permanent discontinuation of RYBREVANT due to adverse reactions occurred in 11% of patients. The most frequent adverse reactions leading to discontinuation of RYBREVANT in ≥ 5% of patients were infusion-related reactions.
Dose interruptions of RYBREVANT due to an adverse reaction occurred in 60% of patients. Infusion-related reactions (IRR) requiring infusion interruptions occurred in 52% of patients. Adverse reactions requiring dose interruption in ≥ 5% of patients included infusion-related reaction, rash and fatigue.
Dose reductions of RYBREVANT due to an adverse reaction occurred in 17% of patients. Adverse reactions requiring dose reductions in ≥ 2% of patients included rash. The most common adverse reactions ≥ 20% were rash, infusion-related reactions, fatigue, nail toxicity, nausea, constipation, edema, stomatitis, decreased appetite, musculoskeletal pain, vomiting, and COVID-19.
Table 12 summarizes the adverse reactions in MARIPOSA-2. 2 Clinically relevant adverse reactions in < 10% of patients who received RYBREVANT in combination with carboplatin and pemetrexed include: abdominal pain, hemorrhoids, dizziness, visual impairment, trichomegaly, keratitis, interstitial lung disease, and skin ulcer.
Table 13 summarizes the laboratory abnormalities in MARIPOSA-2. 3) ] in 151 patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. 9 months). 3). 3% of patients; 89% were not Hispanic or Latino; 86% had baseline body weight < 80 kg.
Serious adverse reactions occurred in 37% of patients who received RYBREVANT in combination with carboplatin and pemetrexed. Serious adverse reactions in ≥ 2% of patients included rash, pneumonia, interstitial lung disease (ILD), pulmonary embolism, vomiting, and COVID-19.
6%) due to pneumonia, cerebrovascular accident, cardio-respiratory arrest, COVID-19, sepsis, and death not otherwise specified. Permanent discontinuation of RYBREVANT due to an adverse reaction occurred in 11% of patients. Adverse reactions resulting in permanent discontinuation of RYBREVANT in ≥ 1% of patients were rash and ILD.
Dose interruptions of RYBREVANT due to an adverse reaction occurred in 64% of patients. Infusion-related reactions (IRR) requiring infusion interruptions occurred in 38% of patients. Adverse reactions requiring dose interruption in ≥ 5% of patients included rash and nail toxicity.
Dose reductions of RYBREVANT due to an adverse reaction occurred in 36% of patients. Adverse reactions requiring dose reductions in ≥ 5% of patients included rash and nail toxicity. The most common adverse reactions (≥ 20%) were rash, nail toxicity, stomatitis, infusion-related reaction, fatigue, edema, constipation, decreased appetite, nausea, COVID-19, diarrhea, and vomiting.
The most common Grade 3 to 4 laboratory abnormalities (≥ 2%) were decreased albumin, increased alanine aminotransferase, increased gamma-glutamyl transferase, decreased sodium, decreased potassium, decreased magnesium, and decreases in white blood cells, hemoglobin, neutrophils, platelets, and lymphocytes.
Table 14 summarizes the adverse reactions in PAPILLON. 0. 7 8 0 Nervous system disorders Dizziness 11 0 12 0 Psychiatric disorders Insomnia 11 0 13 0 Clinically relevant adverse reactions in < 10% of patients who received RYBREVANT in combination with carboplatin and pemetrexed included pulmonary embolism, deep vein thrombosis, skin ulcer, conjunctivitis, and interstitial lung disease (ILD)/pneumonitis.
Table 15 summarizes the laboratory abnormalities in PAPILLON.
Table 15:
Select Laboratory Abnormalities (≥ 20%) That Worsened from Baseline in Patients with Metastatic NSCLC with EGFR Exon 20 Insertion Mutations Who Received RYBREVANT in Combination with Carboplatin and Pemetrexed in PAPILLON RYBREVANT in Combination with Carboplatin and Pemetrexed The denominator used to calculate the rate varied from 113 to 150 based on the number of patients with a baseline value and at least one post-treatment value.
Carboplatin in Combination with Pemetrexed The denominator used to calculate the rate varied from 119 to 154 based on the number of patients with a baseline value and at least one post-treatment value. 4) ], whose disease had progressed on or after platinum-based chemotherapy.
Among patients who received RYBREVANT, 44% were exposed for 6 months or longer and 12% were exposed for greater than one year. 3% were Black; and 82% had baseline body weight < 80 kg. Serious adverse reactions occurred in 30% of patients who received RYBREVANT.
Serious adverse reactions in ≥ 2% of patients included pulmonary embolism, pneumonitis/ILD, dyspnea, musculoskeletal pain, pneumonia, and muscular weakness. 8%) due to sudden death. Permanent discontinuation of RYBREVANT due to an adverse reaction occurred in 11% of patients.
Adverse reactions resulting in permanent discontinuation of RYBREVANT in ≥ 1% of patients were pneumonia, IRR, pneumonitis/ILD, dyspnea, pleural effusion, and rash. Dose interruptions of RYBREVANT due to an adverse reaction occurred in 78% of patients.
Infusion-related reactions (IRR) requiring infusion interruptions occurred in 59% of patients. Adverse reactions requiring dose interruption in ≥ 5% of patients included dyspnea, nausea, rash, vomiting, fatigue, and diarrhea. Dose reductions of RYBREVANT due to an adverse reaction occurred in 15% of patients.
Adverse reactions requiring dose reductions in ≥ 2% of patients included rash and paronychia. The most common adverse reactions (≥ 20%) were rash, IRR, paronychia, musculoskeletal pain, dyspnea, nausea, fatigue, edema, stomatitis, cough, constipation, and vomiting.
The most common Grade 3 to 4 laboratory abnormalities (≥ 2%) were decreased lymphocytes, decreased albumin, decreased phosphate, decreased potassium, increased glucose, increased alkaline phosphatase, increased gamma-glutamyl transferase, and decreased sodium.
Table 16 summarizes the adverse reactions in CHRYSALIS. 8 Clinically relevant adverse reactions in < 10% of patients who received RYBREVANT included ocular toxicity, ILD/pneumonitis, and toxic epidermal necrolysis (TEN). Table 17 summarizes the laboratory abnormalities in CHRYSALIS.
Table 17:
Select Laboratory Abnormalities (≥ 20%) That Worsened from Baseline in Patients With Metastatic NSCLC with EGFR Exon 20 Insertion Mutations Whose Disease Has Progressed on or After Platinum-based Chemotherapy and Who Received RYBREVANT in CHRYSALIS Laboratory Abnormality RYBREVANT The denominator used to calculate the rate was 126 based on the number of patients with a baseline value and at least one post-treatment value.
2 Postmarketing Experience The following adverse reactions associated with the use of RYBREVANT were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Immune system disorders:
Infusion-related reactions, including anaphylaxis/anaphylactic reactions