1 )] . 2 )] . 3 )] . The most common (≥20 %) adverse reactions, including lab abnormalities, were increased aspartate aminotransferase, fatigue, increased alanine aminotransferase, blurred vision, nausea, increased alkaline phosphatase, diarrhea, abdominal pain, keratopathy, peripheral neuropathy, musculoskeletal pain, decreased lymphocytes, decreased platelets, decreased magnesium, decreased hemoglobin, dry eye, constipation, decreased leukocytes, vomiting, decreased albumin, decreased appetite, and decreased neutrophils.
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.
The pooled safety population described in Warnings and Precautions reflect exposure to ELAHERE in 682 patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer at 6 mg/kg AIBW administered intravenously once every 3 weeks until disease progression or unacceptable toxicity in Study 0416, Study 0417, Study 0403 (NCT02631876), and Study 0401 (NCT01609556).
0). In the pooled safety population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were increased aspartate aminotransferase, fatigue, increased alanine aminotransferase, blurred vision, nausea, increased alkaline phosphatase, diarrhea, abdominal pain, keratopathy, peripheral neuropathy, musculoskeletal pain, decreased lymphocytes, decreased platelets, decreased magnesium, decreased hemoglobin, dry eye, constipation, decreased leukocytes, vomiting, decreased albumin, decreased appetite, and decreased neutrophils.
Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Study 0416 The safety of ELAHERE was evaluated in Study 0416, a multicenter, open-label, active-controlled, randomized, two-arm, study in patients (n=453) with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer [see Clinical Studies ( 14 )] .
Patients received ELAHERE 6 mg/kg AIBW once every 3 weeks until disease progression or unacceptable toxicity. 4). Serious adverse reactions occurred in 24% of patients treated with ELAHERE. The most common (≥2%) serious adverse reactions were intestinal obstruction (5%), abdominal pain (3%), and pleural effusion (3%).
Fatal adverse reactions occurred in 3% of patients, including intestinal obstruction, dyspnea in the setting of subileus, neutropenic sepsis, cardiopulmonary failure, respiratory failure, ischemic stroke, and pulmonary embolus. Permanent discontinuation of ELAHERE due to adverse reactions occurred in 9% of patients.
The most common (≥1%) adverse reactions leading to permanent discontinuation were pneumonitis (2%), blurred vision (1%), and peripheral neuropathy (1%). Dosage delays of ELAHERE due to an adverse reaction occurred in 54% of patients treated with ELAHERE.
Adverse reactions which required dosage delays in ≥3% of patients included blurred vision (22%), keratopathy (19%), dry eye (7%), neutropenia (6%), pneumonitis (6%), photophobia (5%), cataract (4%), and peripheral neuropathy (4%). Dose reductions of ELAHERE due to an adverse reaction occurred in 34% of patients.
Adverse reactions which required dose reductions in ≥3% of patients included blurred vision (14%), keratopathy (10%), peripheral neuropathy (6%), and dry eye (5%). Tables 4 and 5 summarize adverse reactions and laboratory abnormalities, respectively, occurring in ≥10% of patients who received ELAHERE in Study 0416.
5 0 ¥ Chemotherapy: paclitaxel, pegylated liposomal doxorubicin (PLD), topotecan. ※ Blurred vision includes vision blurred, vitreous floaters, visual acuity reduced, diplopia, accommodation disorder, and visual impairment. † Keratopathy includes corneal disorder, corneal epithelial microcysts, keratitis, keratopathy, corneal deposits, punctate keratitis, and corneal opacity.
‡ Dry eye includes dry eye and lacrimation increased. ˄ Cataract includes cataract and cataract nuclear. ⸙ Fatigue includes fatigue and asthenia. * Abdominal pain includes abdominal pain, abdominal pain upper, abdominal pain lower, and abdominal discomfort.
¶ Peripheral neuropathy includes neuropathy peripheral, peripheral sensory neuropathy, peripheral motor neuropathy, paresthesia, hypoesthesia, polyneuropathy, neurotoxicity, and peripheral sensorimotor neuropathy. ♦ Musculoskeletal pain includes back pain, myalgia, neck pain, arthralgia, musculoskeletal pain, non-cardiac chest pain, bone pain, pain in extremity, musculoskeletal stiffness, musculoskeletal chest pain, and musculoskeletal discomfort.
± Pneumonitis includes pneumonitis, interstitial lung disease, respiratory failure, and organizing pneumonia. Clinically relevant adverse reactions occurring in <10% of patients who received ELAHERE in Study 0416 included infusion related reactions/hypersensitivity (8%).
Table 5:
Select Laboratory Abnormalities ≥10% for All Grades, in Patients Who Received ELAHERE in Study 0416 Laboratory Abnormality ELAHERE (n=218) Chemotherapy (n=207) All Grades % Grades 3-4 % All Grades % Grades 3-4 % Liver Function Tests Increased aspartate aminotransferase 57 0 14 0 Increased alanine aminotransferase 38 1 15 1 Increased alkaline phosphatase 30 1 13 1 Chemistry Decreased albumin 21 1 27 2 Decreased magnesium 21 1 29 2 Decreased sodium 16 0 18 0 Decreased potassium 15 1 11 1 Increased calcium 12 0 5 0 Decreased bicarbonate 11 0 11 0 Increased creatinine 10 0 11 0 Hematology* Decreased lymphocytes 27 3 42 11 Decreased leukocytes 23 1 53 10 Decreased neutrophils 22 1 45 17 Decreased hemoglobin 18 1 63 8 Decreased platelets 17 1 20 5 * The denominator used to calculate the rate varied from 63 to 214 (ELAHERE); 63 to 194 (IC Chemo) based on the number of patients with a baseline value and at least one post-treatment value.
Study 0417 The safety of ELAHERE was evaluated in Study 0417, a single-arm, open-label study in patients (n=106) with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer [see Clinical Studies ( 14 )] .
Patients received ELAHERE 6 mg/kg AIBW once every 3 weeks until disease progression or unacceptable toxicity. 3). Serious adverse reactions occurred in 31% of patients treated with ELAHERE. The most common (≥2%) serious adverse reactions were intestinal obstruction (8%), ascites (4%), infection (3%), and pleural effusion (3%).
Fatal adverse reactions occurred in 2% of patients, including small intestinal obstruction (1%) and pneumonitis (1%). Permanent discontinuation of ELAHERE due to adverse reactions occurred in 11% of patients. The most common (≥2%) adverse reactions leading to permanent discontinuation were intestinal obstruction (2%) and thrombocytopenia (2%).
9%) permanently discontinued ELAHERE due to visual impairment (unilateral decrease to BCVA ≤ 20/200 that resolved to baseline after discontinuation). Dosage delays of ELAHERE due to an adverse reaction occurred in 39% of patients treated with ELAHERE.
Adverse reactions which required dosage delays in ≥3% of patients included blurred vision (15%), keratopathy (11%), neutropenia (6%), dry eye (5%), cataracts (3%), and increased gamma-glutamyltransferase (3%). Dose reductions of ELAHERE due to an adverse reaction occurred in 20% of patients.
Adverse reactions which required dose reductions in ≥3% of patients included blurred vision (9%) and keratopathy (7%). Table 6 summarizes the adverse reactions (≥10%) in patients treated with ELAHERE in Study 0417.
Table 6:
Adverse Reactions (≥10%) in Patients with Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Received ELAHERE in Study 0417 Adverse Reaction All Grades N=106 (%) Grade 3-4 N=106 (%) Eye disorders Blurred Vision ※ 50 7 Keratopathy † 37 9 Dry eye ‡ 27 2 Cataract 18 3 Photophobia 17 0 Eye pain § 10 0 General disorders Fatigue 49 3 Gastrointestinal disorders Nausea 40 0 Abdominal pain * 36 7 Diarrhea 31 3 Constipation 30 1 Vomiting 19 0 Abdominal distension 11 0 Nervous system disorders Peripheral neuropathy ¶ 33 2 Metabolism and nutrition disorders Decreased appetite 18 1 Musculoskeletal and connective tissue disorders Arthralgia 17 0 Myalgia 10 0 Respiratory, thoracic, and mediastinal disorders Dyspnea^ 12 0 ※ Blurred vision includes vision blurred, vitreous floaters, visual acuity reduced, diplopia, presbyopia, accommodation disorder, visual impairment, and refraction disorder.
† Keratopathy includes corneal disorder, corneal epithelial microcysts, corneal epithelial defect, keratitis, keratopathy, corneal deposits, and punctate keratitis. ‡ Dry eye includes dry eye and lacrimation increased. § Eye pain includes eye pain and ocular discomfort.
⸙ Fatigue includes fatigue and asthenia. * Abdominal pain includes abdominal pain, abdominal pain upper, abdominal pain lower, and abdominal discomfort. ¶ Peripheral neuropathy includes neuropathy peripheral, peripheral sensory neuropathy, peripheral motor neuropathy, paresthesia, hypoesthesia, polyneuropathy, and neurotoxicity.
^ Dyspnea includes dyspnea and exertional dyspnea. Clinically relevant adverse reactions occurring in <10% of patients who received ELAHERE in Study 0417 included infusion related reactions/hypersensitivity (9%), pneumonitis (8%), and uveitis (1%).
Table 7 summarizes the laboratory abnormalities in Study 0417.
Table 7:
Select Laboratory Abnormalities ≥10% for All Grades, or ≥2% for Grades 3-4 in Patients Who Received ELAHERE Laboratory Abnormality ELAHERE* All Grades (%) Grade 3-4 (%) Liver Function Tests Increased aspartate aminotransferase 50 2 Increased alanine aminotransferase 39 2 Increased alkaline phosphatase 30 1 Hematology* Decreased lymphocytes 35 7 Decreased leukocytes 26 1 Decreased neutrophils 26 3 Decreased hemoglobin 25 3 Decreased platelets 18 2 Chemistry Decreased albumin 31 1 Decreased magnesium 27 2 Increased creatinine 16 0 Decreased potassium 15 4 * The denominator used to calculate the rate varied from 98 to 101 based on the number of patients with a baseline value and at least one post-treatment value.
Immunogenicity:
Anti-Drug Antibody-Associated Adverse Reactions In studies 0416, 0417, 0401, and 0403 in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer who received ELAHERE at 6 mg/kg AIBW administered intravenously once every 3 weeks, 9% (57/626) developed anti-drug antibodies.
6 )] .