{"analyses":[{"ciLowerLimit":"2.3","ciNumSides":"TWO_SIDED","ciPctValue":"95","ciUpperLimit":"22.5","estimateComment":"Rate ratio was based on the normal approximation.","groupIds":["OG004","OG006"],"nonInferiorityType":"SUPERIORITY_OR_OTHER","pValue":"<0.0001","pValueComment":"Analysis performed after database lock. P-value was based on the 2-sided Fisher's exact P-value.","paramType":"Rate ratio","paramValue":"7.2","statisticalMethod":"Fisher Exact"},{"ciLowerLimit":"1.4","ciNumSides":"TWO_SIDED","ciPctValue":"95","ciUpperLimit":"14.7","groupIds":["OG005","OG006"],"nonInferiorityType":"SUPERIORITY_OR_OTHER","pValue":"0.0067","pValueComment":"Analysis performed after database lock. P-value was based on the 2-sided Fisher's exact P-value.","paramType":"Rate ratio","paramValue":"4.5","statisticalMethod":"Fisher Exact"},{"ciLowerLimit":"0.9","ciNumSides":"TWO_SIDED","ciPctValue":"95","ciUpperLimit":"2.8","groupIds":["OG004","OG005"],"nonInferiorityType":"SUPERIORITY_OR_OTHER","pValue":"=0.1007","pValueComment":"Analysis performed after database lock. P-value was based on the 2-sided Fisher's exact P-value.","paramType":"Rate ratio","paramValue":"1.6","statisticalMethod":"Fisher Exact"}],"classes":[{"categories":[{"measurements":[{"groupId":"OG004","lowerLimit":"29.3","upperLimit":"57.8","value":"43.1"},{"groupId":"OG005","lowerLimit":"15.6","upperLimit":"41.0","value":"26.9"},{"groupId":"OG006","lowerLimit":"1.3","upperLimit":"16.5","value":"6.0"}]}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"0"},{"groupId":"OG003","value":"0"},{"groupId":"OG004","value":"51"},{"groupId":"OG005","value":"52"},{"groupId":"OG006","value":"50"}],"units":"Participants"}],"description":"The ORR was defined as the percentage of participants who had the best overall response (BOR) of complete response (CR) or partial response (PR) as determined by the investigator, using RECIST 1.1 in the evaluation of MRI or CT scans of targeted lesions. Tumor assessments were performed every 8 weeks (or sooner if there was evidence of progressive disease). The BOR was defined as the best response recorded from the start of the study treatment until discontinuation from the study. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR = CR + PR was calculated with exact 95% CIs using the method of Clopper and Pearson.","dispersionType":"95% Confidence Interval","groups":[{"description":"Oral lenvatinib (12 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in a fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no dose-limiting toxicity (DLT) occurred, then enrollment proceeded to Cohort 2. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 1. If 1 or none of the 6 participants had a DLT, then enrollment proceeded to Cohort 2.\n\nIf 2 or more participants had a DLT during Cycle 1, the dose escalation committee (DEC) decided if they were lenvatinib-related and if enrollment could proceed, lenvatinib was reduced to 6 mg daily (everolimus dose was not reduced). If it could not be determined that the DLTs were lenvatinib-related, enrollment stopped.","id":"OG000","title":"Phase 1b (Cohort 1): 12 mg Lenvatinib Plus 5 mg Everolimus"},{"description":"Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment would proceed to Cohort 3. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 2. If 1 or none of the 6 participants exhibited a DLT, enrollment proceeded to Cohort 3.\n\nIf 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.","id":"OG001","title":"Phase 1b (Cohort 2): 18 mg Lenvatinib Plus 5 mg Everolimus"},{"description":"Oral lenvatinib (24 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment proceeded to Cohort 4. If 1 participant had a DLT, 3 more participants were enrolled Cohort 3. If 1 or none of the 6 participants exhibited a DLT, then enrollment proceeded to Cohort 4.\n\nIf 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.","id":"OG002","title":"Phase 1b (Cohort 3): 24 mg Lenvatinib Plus 5 mg Everolimus"},{"description":"The DLT was achieved and no participants were enrolled into this cohort.","id":"OG003","title":"Phase 1b (Cohort 4): 24 mg Lenvatinib Plus 10 mg Everolimus"},{"description":"Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles. Treatment cycles began with the first dose of study drug in Cycle 1 and continued in 28-day (4-week) consecutive cycles until completion of the off-treatment assessments (within 30 days after the last study treatment administration). Study drugs were administered at the clinic for the first dose and on the pharmacokinetic (PK) sampling days.","id":"OG004","title":"Phase 2 (Arm A): 18 mg Lenvatinib Plus 5 mg Everolimus"},{"description":"Oral lenvatinib (24 mg) was taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles.","id":"OG005","title":"Phase 2 (Arm B): 24 mg Lenvatinib"},{"description":"Oral everolimus (10 mg) was taken once daily in the morning (consistently either with or without food) with water, in continuous 28-day (4-week) cycles.","id":"OG006","title":"Phase 2 (Arm C): 10 mg Everolimus"}],"paramType":"NUMBER","populationDescription":"Full analysis set which included all randomized participants.","reportingStatus":"POSTED","timeFrame":"Randomization (Cycle 1 Day 1) until first evidence of disease progression, assessed up to the data cutoff date (13 Jun 2014), or up to approximately 2 years and 3 months","title":"Phase 2: Objective Response Rate (ORR)","type":"SECONDARY","unitOfMeasure":"Percentage of participants"}