{"classes":[{"categories":[{"measurements":[{"comment":"No AUCtau is included for patients in Cohort B2 DL4B as they do not have the sufficient samples at the necessary time points to calculate a terminal half-life so any estimation would not be reliable.","groupId":"OG000","lowerLimit":"NA","upperLimit":"NA","value":"NA"},{"groupId":"OG001","lowerLimit":"4695.62","upperLimit":"14106.75","value":"6310.38"},{"comment":"No AUCtau is included for patients in Cohort B2 DL3A as they do not have the sufficient samples at the necessary time points to calculate a terminal half-life so any estimation would not be reliable.","groupId":"OG002","lowerLimit":"NA","upperLimit":"NA","value":"NA"},{"groupId":"OG003","lowerLimit":"7594.16","upperLimit":"7594.16","value":"7594.16"}]}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"2"},{"groupId":"OG001","value":"7"},{"groupId":"OG002","value":"1"},{"groupId":"OG003","value":"1"}],"units":"Participants"}],"description":"Steady State AUC for lorlatinib in patients in cohort B2","dispersionType":"Full Range","groups":[{"description":"Lorlatinib will be given orally once daily continuously for 28 days at 95mg/m2/dose. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be under 18 years of age at time of enrollment.\n\nLorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.\n\nCyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle\n\nTopotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle\n\nFilgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC \\> 2000/mm\\^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.\n\nPegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.","id":"OG000","title":"Cohort B2 DL4B"},{"description":"Lorlatinib will be given orally once daily continuously for 28 days at 115mg/m2/dose. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be under 18 years of age at time of enrollment.\n\nLorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.\n\nCyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle\n\nTopotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle\n\nFilgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC \\> 2000/mm\\^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.\n\nPegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.","id":"OG001","title":"Cohort B2 DL5B"},{"description":"Lorlatinib will be given orally once daily continuously for 28 days at 100mg/day. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be 18 years of age or older at time of enrollment.\n\nLorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.\n\nCyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle\n\nTopotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle\n\nFilgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC \\> 2000/mm\\^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.\n\nPegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.","id":"OG002","title":"Cohort B2 DL3A"},{"description":"Lorlatinib will be given orally once daily continuously for 28 days at 150mg/day. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be 18 years of age or older at time of enrollment.\n\nLorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.\n\nCyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle\n\nTopotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle\n\nFilgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC \\> 2000/mm\\^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.\n\nPegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.","id":"OG003","title":"Cohort B2 DL4A"}],"paramType":"MEDIAN","populationDescription":"No AUCtau is included for patients in Cohort B2 DL4B or Cohort B2 DL3A as they do not have the sufficient samples at the necessary time points to calculate a terminal half-life so any estimation would not be reliable.","reportingStatus":"POSTED","timeFrame":"Day 1 through Day 15 (0, 1, 2, 24, 360, 361, 362, 364, 366 hours post-initial dose)","title":"Pharmacokinetics B2-Steady State AUC","type":"SECONDARY","unitOfMeasure":"hours*ng/mL"}