Metastatic Solid Tumors
Conditions
Keywords
INK1117, PIK3CA, KINASE, TUMOR, CANCER, Locally advanced or metastatic solid tumors, not eligible for standard of care therapy
Brief summary
The purpose of this study is to determine the maximum tolerated dose (MTD) and/or optimal biologic dose(OBD), safety and tolerability, dose-limiting toxicity (DLT) of TAK-117 when administered orally in subjects with advanced solid malignancies.
Interventions
DRUGTAK-117
oral administration of TAK-117, daily and intermittent schedules.
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects have had their PIK3CA gene mutation status assessed prior to enrolling into the study * Subjects must have documented disease progression prior to enrolling into the study * locally advanced or metastatic solid tumors with the exception of primary brain tumor, and have failed or are not eligible for standard of care therapy. * Age greater than or equal to (\>=) 18 years, including males and females; * Eastern cooperative oncology group (ECOG) performance status (PS) 0-1; * Adequate organ function; * Male subjects must be surgically sterile or must agree to use physician-approved contraception during the study and for 30 days following the last study drug administration; * Ability to swallow oral medications; * Ability to understand and willingness to sign informed consent prior to initiation of any study procedures; * For women of child-bearing potential, negative serum pregnancy test within 14 days prior to the first study drug administration and use of physician-approved method of birth control from 30 days prior to the first study drug administration to 30 days following the last study drug administration
Exclusion criteria
* Diagnosis of primary brain tumor; untreated brain metastasis or history of leptomeningeal disease or spinal cord compression; * Received prior cancer or other investigational therapy within 2 weeks prior to the first administration of study drug; * Have received a systemic corticosteroid within one week prior to the first administration of study drug; * Clinically significant cardiac disease; * Myocardial infarction or unstable angina within 6 months prior to the first administration of study drug; * Malabsorption ; * Poorly controlled diabetes mellitus; * Pregnancy (positive serum or urine pregnancy test) or breast feeding; * Untreated brain metastasis or history of leptomeningeal disease or spinal cord compression; * Failed to recover from the reversible effects of prior anticancer therapies; * Have received a selective phosphoinositide-3-kinase alpha isoform (PI3K-alpha) inhibitor * Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system (CNS) disease, active infection, or any other condition that could compromise the subject's participation in the study * Known human immunodeficiency virus (HIV) infection * Have a secondary malignancy within the last 3 years prior to first dose of study drug, excluding treated non-melanoma skin cancer, carcinoma in situ, or locally-treated prostate cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of TAK-117 | Baseline up to Cycle 1 Day 21 | MTD is highest dose level of TAK-117 at which no more than 1 out of 6 participants had a dose limiting toxicity (DLT) during first cycle. DLT was any 1 of following events occurring within first 21 days of Cycle 1 of TAK-117 administration, Grade 2: fasting hyperglycemia for \>14 days. Grade 3: nausea and/or vomiting/diarrhea for \>7 days; rash for \>7 days; thrombocytopenia with bleeding; fasting hyperglycemia for \>24 hours(hr). Grade \>=3:nonhematologic toxicity considered clinically significant by investigator. Grade 4:neutropenia (absolute neutrophil count \<=0.5\*10\^9per liter\[/L\]) for \>7 days in absence of growth factor support; neutropenia of any duration accompanied with fever \>=38.5 degree Celsius and/or systemic infection. Grade \>=4:hematologic toxicity. Inability to administer at least 75% of planned doses of TAK-117 within Cycle 1 due to its related toxicity;Any clinically significant occurrence that investigators and sponsor agreed would place participants at undue safety risk. |
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Baseline up to Cycle 27 Day 45 | — |
| Number of Participants With Highest Level of TEAEs Severity | Baseline up to Cycle 27 Day 45 | Severity of AEs was evaluated based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0 as follow: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); Grade 4 (life-threatening); Grade 5 (fatal). |
| Number of Participants With Clinically Meaningful Changes in Laboratory Values | Baseline up to Cycle 27 Day 45 | — |
| Number of Participants With Clinically Meaningful Changes in Vital Signs | Baseline up to Cycle 27 day 45 | — |
| Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | Baseline up to Cycle 27 Day 45 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| T 1/2z: Terminal Disposition Phase Half-life for TAK-117 | Process A: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 24 hrs) post-dose; Process B: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 48 hrs) post-dose | — |
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117 | Process A: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 24 hrs) post-dose; Process B: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 48 hrs) post-dose | — |
| Clinical Benefit Rate (CBR) | Cycle 1 Day 8 up to Cycle 27 Day 1 or disease progression or death | Clinical benefit rate was defined as the participants who achieved stable disease (SD) for at least 15 weeks, CR, or PR. The estimate of the CBR was calculated as crude percentage of participants whose best ORR was CR, PR or SD for at least 90 days. |
| %AUC Extrapolated: Percentage of Area Under Concentration-extrapolated | Process A: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 24 hrs) post-dose; Process B: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 48 hrs) post-dose | — |
| Percent Change From Baseline in Pharmacodynamic Markers | Cycle 1 Day 8 | Pharmacodynamic markers included phosphorylated ribosomal protein S6 (PS6), phosphorylated eukaryotic initiation factor 4E-binding protein 1 (P4EBP1), phosphorylated N-myc downstream regulated gene 1 (PNDRG1), phosphorylated proline-rich AKT substrate of 40 kilodaltons (PPRAS40), and phosphorylated serine/threonine protein kinase AKT (PAKT). Analysis population (n) for each skin biopsy biomarker is as follow: P4EBP1 (n=6,6,6,2,2,0,0,0,0,1,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0); PAKT and PNDRG1 (n=6,6,7,2,2,0,0,0,0,1,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0); PPRAS40 (n= 6,0,6,2,2,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0); PS6 (n=6,6,7,2,2,0,0,0,0,1,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0).n for each tumor tissue biomarkers is as follow: P4EBP1, PAKT, PNDRG1, and PS6 (n=1,1,0,0,1,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0); PPRAS40 (n= 1,0,0,0,1,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0). |
| AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-117 | Process A: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 24 hrs) post-dose; Process B: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 48 hrs) post-dose | — |
| Overall Response Rate (ORR) | Cycle 1 Day 8 up to Cycle 27 Day 1 or disease progression or death | The estimate of the ORR is calculated as crude percentage of participants who's best overall response is complete response (CR) or partial response (PR). Objective response (CR and PR) as determined by the participants best tumor response was assessed using response evaluation criteria in solid tumors (RECIST) version 1.1. As per RECIST version 1.1, CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 millimeter \[mm\]). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. Stable disease was defined as not qualifying for CR, PR, and progressive disease (PD). |
| Duration of Objective Response | Cycle 1 Day 8 up to Cycle 27 Day 1 or disease progression or death | Duration of response was to be calculated for participants who achieved CR or PR. Duration of objective response was defined as the number of days from the start date of PR or CR (whichever response was achieved first) to the first date that PD or disease progression was objectively documented. The duration of objective response was to be right-censored for participants who achieved CR or PR and met 1 of the following conditions: Non-protocol anticancer treatment started before documentation of PD; Documented PD after more than 1 missed disease assessment visit; Alive and did not have documentation of PD before a data analysis cutoff date. |
| Cmax: Maximum Observed Plasma Concentration for TAK-117 | Process A: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 24 hrs) post-dose; Process B: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 48 hrs) post-dose | — |
| Ctrough: Observed Concentration at the End of Dosing Interval for TAK-117 | Process A: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 24 hrs) post-dose; Process B: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 48 hrs) post-dose | — |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117 | Process A: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 24 hrs) post-dose; Process B: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 48 hrs) post-dose | — |
Countries
Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants took part in the study at 5 investigative sites in England, Spain and the United States from 06 October 2011 to 15 January 2016.
Pre-assignment details
Participants with advanced solid tumors were enrolled in dose escalation phase to receive TAK-117(MLN1117) in 1 of 4 treatment regimen.Study originally used clinical trial material(CTM) in Process A and new CTM in Process B. Due to limited single-agent TAK-117 activity in dose escalation phase,Study was terminated before start of planned expansion.
Participants by arm
| Arm | Count |
|---|---|
| Process A: TAK-117 100 Milligram (mg), Once Daily (QD) TAK-117 100 mg, capsules (Process A), orally, QD up to Day 15 of each treatment cycle. Treatment cycle were repeated every 21 days. | 6 |
| Process A: TAK-117 150 mg, QD TAK-117 150 mg, capsules (Process A), orally, QD up to Day 15 of each treatment cycle. Treatment cycle were repeated every 21 days. | 6 |
| Process A: TAK-117 200 mg, QD TAK-117 200 mg, capsules (Process A), orally, QD up to Day 15 of each treatment cycle. Treatment cycle were repeated every 21 days. | 8 |
| Process A: TAK-117 300 mg, QD TAK-117 300 mg, capsules (Process A), orally, QD up to Day 15 of each treatment cycle. Treatment cycle were repeated every 21 days. | 4 |
| Process A: TAK-117 200 mg, MWF QW TAK-117 200 mg, capsules (Process A), orally, once every other day on Monday, Wednesday, and Friday each week (MWF QW) up to Day 15 of each treatment cycle. Treatment cycles were repeated every 21 days. | 3 |
| Process A: TAK-117 300 mg, MWF QW TAK-117 300 mg, capsules (Process A), orally, once every other day on MWF QW up to Day 15 of each treatment cycle. Treatment cycles were repeated every 21 days. | 3 |
| Process A: TAK-117 400 mg, MWF QW TAK-117 400 mg, capsules (Process A), orally, once every other day on MWF QW up to Day 15 of each treatment cycle. Treatment cycles were repeated every 21 days. | 3 |
| Process A: TAK-117 600 mg, MWF QW TAK-117 600 mg, capsules (Process A), orally, once every other day on MWF QW up to Day 15 of each treatment cycle. Treatment cycles were repeated every 21 days. | 3 |
| Process A: TAK-117 900 mg, MWF QW TAK-117 900 mg, capsules (Process A), orally, once every other day on MWF QW up to Day 15 of each treatment cycle. Treatment cycles were repeated every 21 days. | 12 |
| Process A: TAK-117 1200 mg, MWF QW TAK-117 1200 mg, capsules (Process A), orally, once every other day on MWF QW up to Day 15 of each treatment cycle. Treatment cycles were repeated every 21 days. | 3 |
| Process A: TAK-117 200 mg, MTW QW TAK-117 200 mg, capsules (Process A), orally, QD for 3 consecutive days, on Monday, Tuesday, and Wednesday each week (MTW QW) up to Day 15 of each treatment cycle. Treatment cycles were repeated every 21 days. | 3 |
| Process A: TAK-117 400 mg, MTW QW TAK-117 400 mg, capsules (Process A), orally, QD for 3 consecutive days, on MTW QW up to Day 15 of each treatment cycle. Treatment cycles were repeated every 21 days. | 3 |
| Process A: TAK-117 600 mg, MTW QW TAK-117 600 mg, capsules (Process A), orally, QD for 3 consecutive days, on MTW QW up to Day 15 of each treatment cycle. Treatment cycles were repeated every 21 days. | 3 |
| Process A: TAK-117 900 mg, MTW QW TAK-117 900 mg, capsules (Process A), orally, QD for 3 consecutive days, on MTW QW up to Day 15 of each treatment cycle. Treatment cycles were repeated every 21 days. | 11 |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW TAK-117 600 mg, capsules (Process B), orally, once every other day on MWF QW up to Day 15 of each treatment cycle. Treatment cycles were repeated every 21 days. FM used drug substance manufactured by an improved synthetic process. | 3 |
| Process B: TAK-117 900 mg FM MWF QW TAK-117 900 mg, capsules (Process B), orally, once every other day on MWF QW up to Day 15 of each treatment cycle. Treatment cycles were repeated every 21 days. FM used drug substance manufactured by an improved synthetic process. | 3 |
| Process B: TAK-117 1200 mg FM MWF QW TAK-117 1200 mg, capsules (Process B), orally, once every other day on MWF QW up to Day 15 of each treatment cycle. Treatment cycles were repeated every 21 days. FM used drug substance manufactured by an improved synthetic process. | 7 |
| Process B: TAK-117 600 mg FM MTW QW TAK-117 600 mg, capsules (Process B), orally, QD for 3 consecutive days, on MTW QW up to Day 15 of each treatment cycle. Treatment cycles were repeated every 21 days. FM used drug substance manufactured by an improved synthetic process. | 3 |
| Process B: TAK-117 900 mg FM MTW QW TAK-117 900 mg, capsules (Process B), orally, QD for 3 consecutive days, on MTW QW up to Day 15 of each treatment cycle. Treatment cycles were repeated every 21 days. FM used drug substance manufactured by an improved synthetic process. | 3 |
| Process B: TAK-117 1200 mg FM MTW QW TAK-117 1200 mg, capsules (Process B), orally, QD for 3 consecutive days, on MTW QW up to Day 15 of each treatment cycle. Treatment cycles were repeated every 21 days. FM used drug substance manufactured by an improved synthetic process. | 3 |
| Process B: TAK-117 1500 mg FM MTW QW TAK-117 1500 mg, capsules (Process B), orally, QD for 3 consecutive days, on MTW QW up to Day 15 of each treatment cycle. Treatment cycles were repeated every 21 days. FM used drug substance manufactured by an improved synthetic process. | 6 |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW TAK-117 300 mg, capsules (Process B), orally, BID every other day on MWF QW up to Day 15 of each treatment cycle. Treatment cycles were repeated every 21 days. FM used drug substance manufactured by an improved synthetic process. | 4 |
| Process B: TAK-117 400 mg FM BID MWF QW TAK-117 400 mg, capsules (Process B), orally, intermittently, BID every other day on MWF QW up to Day 15 of each treatment cycle. Treatment cycles were repeated every 21 days. FM used drug substance manufactured by an improved synthetic process. | 4 |
| Process B: TAK-117 500 mg FM BID MWF QW TAK-117 500 mg, capsules (Process B), orally, intermittently, BID every other day on MWF QW up to Day 15 of each treatment cycle. Treatment cycles were repeated every 21 days. FM used drug substance manufactured by an improved synthetic process. | 10 |
| Process B: TAK-117 600 mg FM BID MWF QW TAK-117 600 mg, capsules (Process B), orally, intermittently, BID every other day on MWF QW up to Day 15 of each treatment cycle. Treatment cycles were repeated every 21 days. FM used drug substance manufactured by an improved synthetic process. | 8 |
| Total | 125 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 | FG019 | FG020 | FG021 | FG022 | FG023 | FG024 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 1 | 3 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Disease Progression | 5 | 4 | 8 | 3 | 3 | 3 | 3 | 2 | 9 | 1 | 3 | 3 | 2 | 8 | 3 | 1 | 4 | 3 | 1 | 2 | 5 | 2 | 3 | 7 | 3 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Medication Prohibited by Protocol | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Participant Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 3 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Process B: TAK-117 1200 mg FM MTW QW | Process A: TAK-117 100 Milligram (mg), Once Daily (QD) | Process A: TAK-117 150 mg, QD | Process A: TAK-117 200 mg, QD | Process A: TAK-117 300 mg, QD | Process A: TAK-117 200 mg, MWF QW | Process A: TAK-117 300 mg, MWF QW | Process A: TAK-117 400 mg, MWF QW | Process A: TAK-117 600 mg, MWF QW | Process A: TAK-117 900 mg, MWF QW | Process A: TAK-117 1200 mg, MWF QW | Process A: TAK-117 200 mg, MTW QW | Process A: TAK-117 400 mg, MTW QW | Process A: TAK-117 600 mg, MTW QW | Process A: TAK-117 900 mg, MTW QW | Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Process B: TAK-117 900 mg FM MWF QW | Process B: TAK-117 1200 mg FM MWF QW | Process B: TAK-117 600 mg FM MTW QW | Process B: TAK-117 900 mg FM MTW QW | Process B: TAK-117 1500 mg FM MTW QW | Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Process B: TAK-117 400 mg FM BID MWF QW | Process B: TAK-117 500 mg FM BID MWF QW | Process B: TAK-117 600 mg FM BID MWF QW | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 66.7 years STANDARD_DEVIATION 2.52 | 64.7 years STANDARD_DEVIATION 9.79 | 59.0 years STANDARD_DEVIATION 10.88 | 59.3 years STANDARD_DEVIATION 9.05 | 45.3 years STANDARD_DEVIATION 7.27 | 56.3 years STANDARD_DEVIATION 17.67 | 52.7 years STANDARD_DEVIATION 14.01 | 54.3 years STANDARD_DEVIATION 12.58 | 65.0 years STANDARD_DEVIATION 13.11 | 56.4 years STANDARD_DEVIATION 13.28 | 53.3 years STANDARD_DEVIATION 19.4 | 64.7 years STANDARD_DEVIATION 18.58 | 50.0 years STANDARD_DEVIATION 11.53 | 55.0 years STANDARD_DEVIATION 9.54 | 57.4 years STANDARD_DEVIATION 10.88 | 65.7 years STANDARD_DEVIATION 12.86 | 62.7 years STANDARD_DEVIATION 16.17 | 61.0 years STANDARD_DEVIATION 11.89 | 52.7 years STANDARD_DEVIATION 19.76 | 53.7 years STANDARD_DEVIATION 1.53 | 61.3 years STANDARD_DEVIATION 13.68 | 72.5 years STANDARD_DEVIATION 4.65 | 60.3 years STANDARD_DEVIATION 11.81 | 66.0 years STANDARD_DEVIATION 8.71 | 59.5 years STANDARD_DEVIATION 10.39 | 59.4 years STANDARD_DEVIATION 11.89 |
| Body Surface Area (BSA) | 1.70 square meter (m^2) STANDARD_DEVIATION 0.25 | 1.67 square meter (m^2) STANDARD_DEVIATION 0.108 | 1.78 square meter (m^2) STANDARD_DEVIATION 0.266 | 1.83 square meter (m^2) STANDARD_DEVIATION 0.152 | 1.85 square meter (m^2) STANDARD_DEVIATION 0.5 | 1.81 square meter (m^2) STANDARD_DEVIATION 0.241 | 1.66 square meter (m^2) STANDARD_DEVIATION 0.06 | 1.63 square meter (m^2) STANDARD_DEVIATION 0.041 | 1.70 square meter (m^2) STANDARD_DEVIATION 0.063 | 1.76 square meter (m^2) STANDARD_DEVIATION 0.248 | 1.69 square meter (m^2) STANDARD_DEVIATION 0.192 | 1.81 square meter (m^2) STANDARD_DEVIATION 0.209 | 1.99 square meter (m^2) STANDARD_DEVIATION 0.354 | 1.66 square meter (m^2) STANDARD_DEVIATION 0.11 | 1.85 square meter (m^2) STANDARD_DEVIATION 0.214 | 1.85 square meter (m^2) STANDARD_DEVIATION 0.151 | 1.88 square meter (m^2) STANDARD_DEVIATION 0.235 | 1.92 square meter (m^2) STANDARD_DEVIATION 0.21 | 1.95 square meter (m^2) STANDARD_DEVIATION 0.384 | 1.97 square meter (m^2) STANDARD_DEVIATION 0.262 | 1.72 square meter (m^2) STANDARD_DEVIATION 0.253 | 1.80 square meter (m^2) STANDARD_DEVIATION 0.217 | 1.68 square meter (m^2) STANDARD_DEVIATION 0.154 | 1.82 square meter (m^2) STANDARD_DEVIATION 0.256 | 1.71 square meter (m^2) STANDARD_DEVIATION 0.17 | 1.79 square meter (m^2) STANDARD_DEVIATION 0.219 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 5 Participants | 6 Participants | 6 Participants | 4 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 11 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 11 Participants | 3 Participants | 3 Participants | 7 Participants | 3 Participants | 3 Participants | 6 Participants | 4 Participants | 4 Participants | 9 Participants | 7 Participants | 117 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants |
| Female Child Bearing Potential Females of Child-bearing Potential | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants | 7 participants |
| Female Child Bearing Potential Males (Excluded from this analysis) | 1 participants | 2 participants | 2 participants | 3 participants | 1 participants | 1 participants | 1 participants | 1 participants | 0 participants | 3 participants | 0 participants | 2 participants | 2 participants | 0 participants | 4 participants | 2 participants | 2 participants | 2 participants | 2 participants | 1 participants | 2 participants | 0 participants | 0 participants | 5 participants | 2 participants | 41 participants |
| Female Child Bearing Potential Post-menopausal | 1 participants | 4 participants | 3 participants | 3 participants | 0 participants | 1 participants | 1 participants | 1 participants | 1 participants | 4 participants | 2 participants | 0 participants | 0 participants | 2 participants | 2 participants | 0 participants | 1 participants | 4 participants | 1 participants | 2 participants | 4 participants | 4 participants | 3 participants | 3 participants | 4 participants | 51 participants |
| Female Child Bearing Potential Sterilized Females | 1 participants | 0 participants | 1 participants | 1 participants | 2 participants | 0 participants | 1 participants | 1 participants | 2 participants | 4 participants | 1 participants | 1 participants | 0 participants | 1 participants | 5 participants | 1 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 2 participants | 26 participants |
| Gender Female | 2 Participants | 4 Participants | 4 Participants | 5 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 9 Participants | 3 Participants | 1 Participants | 1 Participants | 3 Participants | 7 Participants | 1 Participants | 1 Participants | 5 Participants | 1 Participants | 2 Participants | 4 Participants | 4 Participants | 4 Participants | 5 Participants | 6 Participants | 84 Participants |
| Gender Male | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 4 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 5 Participants | 2 Participants | 41 Participants |
| Height | 168.11 centimeter (cm) STANDARD_DEVIATION 6.887 | 161.70 centimeter (cm) STANDARD_DEVIATION 10.758 | 164.29 centimeter (cm) STANDARD_DEVIATION 7.241 | 165.25 centimeter (cm) STANDARD_DEVIATION 9.403 | 164.15 centimeter (cm) STANDARD_DEVIATION 5.837 | 164.19 centimeter (cm) STANDARD_DEVIATION 5.195 | 161.81 centimeter (cm) STANDARD_DEVIATION 5.222 | 165.17 centimeter (cm) STANDARD_DEVIATION 7.848 | 163.49 centimeter (cm) STANDARD_DEVIATION 6.883 | 163.08 centimeter (cm) STANDARD_DEVIATION 12.871 | 158.76 centimeter (cm) STANDARD_DEVIATION 9.161 | 168.76 centimeter (cm) STANDARD_DEVIATION 2.043 | 173.43 centimeter (cm) STANDARD_DEVIATION 6.072 | 164.67 centimeter (cm) STANDARD_DEVIATION 3.055 | 167.46 centimeter (cm) STANDARD_DEVIATION 10.274 | 170.22 centimeter (cm) STANDARD_DEVIATION 1.683 | 168.93 centimeter (cm) STANDARD_DEVIATION 16.176 | 168.32 centimeter (cm) STANDARD_DEVIATION 4.243 | 169.83 centimeter (cm) STANDARD_DEVIATION 13.829 | 169.52 centimeter (cm) STANDARD_DEVIATION 8.713 | 165.97 centimeter (cm) STANDARD_DEVIATION 6.472 | 159.00 centimeter (cm) STANDARD_DEVIATION 3.939 | 157.05 centimeter (cm) STANDARD_DEVIATION 3.316 | 168.79 centimeter (cm) STANDARD_DEVIATION 13.186 | 164.87 centimeter (cm) STANDARD_DEVIATION 9.638 | 165.49 centimeter (cm) STANDARD_DEVIATION 9.098 |
| Race/Ethnicity, Customized Asian | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 3 participants |
| Race/Ethnicity, Customized Black or African American | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 4 participants |
| Race/Ethnicity, Customized Not Reported | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Other | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized White | 3 participants | 6 participants | 6 participants | 8 participants | 3 participants | 3 participants | 2 participants | 1 participants | 3 participants | 12 participants | 3 participants | 3 participants | 1 participants | 3 participants | 11 participants | 2 participants | 2 participants | 7 participants | 3 participants | 3 participants | 6 participants | 3 participants | 3 participants | 10 participants | 8 participants | 115 participants |
| Weight | 62.61 kilogram (kg) STANDARD_DEVIATION 15.706 | 62.18 kilogram (kg) STANDARD_DEVIATION 6.403 | 71.15 kilogram (kg) STANDARD_DEVIATION 21.862 | 73.48 kilogram (kg) STANDARD_DEVIATION 9.159 | 67.65 kilogram (kg) STANDARD_DEVIATION 24.513 | 72.48 kilogram (kg) STANDARD_DEVIATION 17.665 | 61.54 kilogram (kg) STANDARD_DEVIATION 2.487 | 57.73 kilogram (kg) STANDARD_DEVIATION 0.462 | 63.41 kilogram (kg) STANDARD_DEVIATION 3.88 | 69.14 kilogram (kg) STANDARD_DEVIATION 15.486 | 65.03 kilogram (kg) STANDARD_DEVIATION 15.137 | 70.76 kilogram (kg) STANDARD_DEVIATION 16.458 | 83.39 kilogram (kg) STANDARD_DEVIATION 28.852 | 60.60 kilogram (kg) STANDARD_DEVIATION 9.016 | 73.78 kilogram (kg) STANDARD_DEVIATION 12.955 | 72.26 kilogram (kg) STANDARD_DEVIATION 11.235 | 75.22 kilogram (kg) STANDARD_DEVIATION 12.679 | 79.84 kilogram (kg) STANDARD_DEVIATION 16.648 | 81.07 kilogram (kg) STANDARD_DEVIATION 25.417 | 82.72 kilogram (kg) STANDARD_DEVIATION 17.982 | 64.59 kilogram (kg) STANDARD_DEVIATION 16.477 | 73.65 kilogram (kg) STANDARD_DEVIATION 16.747 | 65.37 kilogram (kg) STANDARD_DEVIATION 11.853 | 70.51 kilogram (kg) STANDARD_DEVIATION 15.263 | 65.11 kilogram (kg) STANDARD_DEVIATION 9.599 | 70.17 kilogram (kg) STANDARD_DEVIATION 14.958 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk | EG021 affected / at risk | EG022 affected / at risk | EG023 affected / at risk | EG024 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 8 / 8 | 4 / 4 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 12 / 12 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 11 / 11 | 3 / 3 | 3 / 3 | 7 / 7 | 3 / 3 | 3 / 3 | 3 / 3 | 6 / 6 | 2 / 4 | 4 / 4 | 10 / 10 | 7 / 8 |
| serious Total, serious adverse events | 2 / 6 | 3 / 6 | 4 / 8 | 2 / 4 | 0 / 3 | 2 / 3 | 0 / 3 | 2 / 3 | 5 / 12 | 2 / 3 | 0 / 3 | 1 / 3 | 0 / 3 | 7 / 11 | 1 / 3 | 2 / 3 | 2 / 7 | 1 / 3 | 1 / 3 | 1 / 3 | 2 / 6 | 1 / 4 | 1 / 4 | 5 / 10 | 5 / 8 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of TAK-117
MTD is highest dose level of TAK-117 at which no more than 1 out of 6 participants had a dose limiting toxicity (DLT) during first cycle. DLT was any 1 of following events occurring within first 21 days of Cycle 1 of TAK-117 administration, Grade 2: fasting hyperglycemia for \>14 days. Grade 3: nausea and/or vomiting/diarrhea for \>7 days; rash for \>7 days; thrombocytopenia with bleeding; fasting hyperglycemia for \>24 hours(hr). Grade \>=3:nonhematologic toxicity considered clinically significant by investigator. Grade 4:neutropenia (absolute neutrophil count \<=0.5\*10\^9per liter\[/L\]) for \>7 days in absence of growth factor support; neutropenia of any duration accompanied with fever \>=38.5 degree Celsius and/or systemic infection. Grade \>=4:hematologic toxicity. Inability to administer at least 75% of planned doses of TAK-117 within Cycle 1 due to its related toxicity;Any clinically significant occurrence that investigators and sponsor agreed would place participants at undue safety risk.
Time frame: Baseline up to Cycle 1 Day 21
Population: The ASat population included all enrolled participants who received at least 1 dose of TAK-117.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Process A: Total QD TAK-117 100-300 mg | Maximum Tolerated Dose (MTD) of TAK-117 | 150 mg |
| Process A: Total MWF QW 200-1200 mg | Maximum Tolerated Dose (MTD) of TAK-117 | 900 mg |
| Process A: Total MTW QW 200-900 mg | Maximum Tolerated Dose (MTD) of TAK-117 | 900 mg |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Maximum Tolerated Dose (MTD) of TAK-117 | NA mg |
| Process B: Total FM MTW QW 600-1500 mg | Maximum Tolerated Dose (MTD) of TAK-117 | NA mg |
| Process B: Total FM BID MWF QW 300-600 mg | Maximum Tolerated Dose (MTD) of TAK-117 | 500 mg |
Primary
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1
Time frame: Baseline up to Cycle 27 Day 45
Population: The ASat population included all enrolled participants who received at least 1 dose of TAK-117.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Process A: Total QD TAK-117 100-300 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 2 participants |
| Process A: Total QD TAK-117 100-300 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 6 participants |
| Process A: Total QD TAK-117 100-300 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 1 participants |
| Process A: Total QD TAK-117 100-300 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 0 participants |
| Process A: Total QD TAK-117 100-300 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 0 participants |
| Process A: Total MWF QW 200-1200 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 2 participants |
| Process A: Total MWF QW 200-1200 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 1 participants |
| Process A: Total MWF QW 200-1200 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 6 participants |
| Process A: Total MWF QW 200-1200 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 0 participants |
| Process A: Total MWF QW 200-1200 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 3 participants |
| Process A: Total MTW QW 200-900 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 4 participants |
| Process A: Total MTW QW 200-900 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 0 participants |
| Process A: Total MTW QW 200-900 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 2 participants |
| Process A: Total MTW QW 200-900 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 1 participants |
| Process A: Total MTW QW 200-900 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 8 participants |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 1 participants |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 4 participants |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 2 participants |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 0 participants |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 1 participants |
| Process B: Total FM MTW QW 600-1500 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 0 participants |
| Process B: Total FM MTW QW 600-1500 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 3 participants |
| Process B: Total FM MTW QW 600-1500 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 0 participants |
| Process B: Total FM MTW QW 600-1500 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 0 participants |
| Process B: Total FM MTW QW 600-1500 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 0 participants |
| Process B: Total FM BID MWF QW 300-600 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 1 participants |
| Process B: Total FM BID MWF QW 300-600 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 3 participants |
| Process B: Total FM BID MWF QW 300-600 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 0 participants |
| Process B: Total FM BID MWF QW 300-600 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 2 participants |
| Process B: Total FM BID MWF QW 300-600 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 0 participants |
| Process A: TAK-117 400 mg, MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 0 participants |
| Process A: TAK-117 400 mg, MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 3 participants |
| Process A: TAK-117 400 mg, MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 0 participants |
| Process A: TAK-117 400 mg, MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 0 participants |
| Process A: TAK-117 400 mg, MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 0 participants |
| Process A: TAK-117 600 mg, MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 2 participants |
| Process A: TAK-117 600 mg, MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 0 participants |
| Process A: TAK-117 600 mg, MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 1 participants |
| Process A: TAK-117 600 mg, MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 0 participants |
| Process A: TAK-117 600 mg, MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 3 participants |
| Process A: TAK-117 900 mg, MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 12 participants |
| Process A: TAK-117 900 mg, MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 1 participants |
| Process A: TAK-117 900 mg, MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 2 participants |
| Process A: TAK-117 900 mg, MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 1 participants |
| Process A: TAK-117 900 mg, MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 5 participants |
| Process A: TAK-117 1200 mg, MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 2 participants |
| Process A: TAK-117 1200 mg, MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 3 participants |
| Process A: TAK-117 1200 mg, MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 0 participants |
| Process A: TAK-117 1200 mg, MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 2 participants |
| Process A: TAK-117 1200 mg, MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 1 participants |
| Process A: TAK-117 200 mg, MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 0 participants |
| Process A: TAK-117 200 mg, MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 0 participants |
| Process A: TAK-117 200 mg, MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 0 participants |
| Process A: TAK-117 200 mg, MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 0 participants |
| Process A: TAK-117 200 mg, MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 3 participants |
| Process A: TAK-117 400 mg, MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 1 participants |
| Process A: TAK-117 400 mg, MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 1 participants |
| Process A: TAK-117 400 mg, MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 3 participants |
| Process A: TAK-117 400 mg, MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 0 participants |
| Process A: TAK-117 400 mg, MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 0 participants |
| Process A: TAK-117 600 mg, MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 0 participants |
| Process A: TAK-117 600 mg, MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 3 participants |
| Process A: TAK-117 600 mg, MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 0 participants |
| Process A: TAK-117 600 mg, MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 0 participants |
| Process A: TAK-117 600 mg, MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 0 participants |
| Process A: TAK-117 900 mg, MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 1 participants |
| Process A: TAK-117 900 mg, MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 2 participants |
| Process A: TAK-117 900 mg, MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 11 participants |
| Process A: TAK-117 900 mg, MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 7 participants |
| Process A: TAK-117 900 mg, MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 0 participants |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 0 participants |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 0 participants |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 1 participants |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 0 participants |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 3 participants |
| Process B: TAK-117 900 mg FM MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 2 participants |
| Process B: TAK-117 900 mg FM MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 0 participants |
| Process B: TAK-117 900 mg FM MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 1 participants |
| Process B: TAK-117 900 mg FM MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 1 participants |
| Process B: TAK-117 900 mg FM MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 3 participants |
| Process B: TAK-117 1200 mg FM MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 7 participants |
| Process B: TAK-117 1200 mg FM MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 0 participants |
| Process B: TAK-117 1200 mg FM MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 0 participants |
| Process B: TAK-117 1200 mg FM MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 2 participants |
| Process B: TAK-117 1200 mg FM MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 1 participants |
| Process B: TAK-117 600 mg FM MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 3 participants |
| Process B: TAK-117 600 mg FM MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 0 participants |
| Process B: TAK-117 600 mg FM MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 1 participants |
| Process B: TAK-117 600 mg FM MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 0 participants |
| Process B: TAK-117 600 mg FM MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 0 participants |
| Process B: TAK-117 900 mg FM MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 1 participants |
| Process B: TAK-117 900 mg FM MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 1 participants |
| Process B: TAK-117 900 mg FM MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 0 participants |
| Process B: TAK-117 900 mg FM MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 0 participants |
| Process B: TAK-117 900 mg FM MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 3 participants |
| Process B: TAK-117 1200 mg FM MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 3 participants |
| Process B: TAK-117 1200 mg FM MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 1 participants |
| Process B: TAK-117 1200 mg FM MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 1 participants |
| Process B: TAK-117 1200 mg FM MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 1 participants |
| Process B: TAK-117 1200 mg FM MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 0 participants |
| Process B: TAK-117 1500 mg FM MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 2 participants |
| Process B: TAK-117 1500 mg FM MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 0 participants |
| Process B: TAK-117 1500 mg FM MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 6 participants |
| Process B: TAK-117 1500 mg FM MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 0 participants |
| Process B: TAK-117 1500 mg FM MTW QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 1 participants |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 0 participants |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 1 participants |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 3 participants |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 1 participants |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 1 participants |
| Process B: TAK-117 400 mg FM BID MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 1 participants |
| Process B: TAK-117 400 mg FM BID MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 4 participants |
| Process B: TAK-117 400 mg FM BID MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 0 participants |
| Process B: TAK-117 400 mg FM BID MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 0 participants |
| Process B: TAK-117 400 mg FM BID MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 1 participants |
| Process B: TAK-117 500 mg FM BID MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 1 participants |
| Process B: TAK-117 500 mg FM BID MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 10 participants |
| Process B: TAK-117 500 mg FM BID MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 5 participants |
| Process B: TAK-117 500 mg FM BID MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 0 participants |
| Process B: TAK-117 500 mg FM BID MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 0 participants |
| Process B: TAK-117 600 mg FM BID MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | TEAE | 7 participants |
| Process B: TAK-117 600 mg FM BID MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | SAE | 5 participants |
| Process B: TAK-117 600 mg FM BID MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | AEs leading to discontinuation of study drug | 4 participants |
| Process B: TAK-117 600 mg FM BID MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | DLTs in Cycle 1 | 1 participants |
| Process B: TAK-117 600 mg FM BID MWF QW | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1 | Death | 1 participants |
Primary
Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG)
Time frame: Baseline up to Cycle 27 Day 45
Population: The ASat population included all enrolled participants who received at least 1 dose of TAK-117.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Process A: Total QD TAK-117 100-300 mg | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
| Process A: Total MWF QW 200-1200 mg | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
| Process A: Total MTW QW 200-900 mg | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
| Process B: Total FM MTW QW 600-1500 mg | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
| Process B: Total FM BID MWF QW 300-600 mg | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
| Process A: TAK-117 400 mg, MWF QW | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
| Process A: TAK-117 600 mg, MWF QW | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
| Process A: TAK-117 900 mg, MWF QW | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
| Process A: TAK-117 1200 mg, MWF QW | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
| Process A: TAK-117 200 mg, MTW QW | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
| Process A: TAK-117 400 mg, MTW QW | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
| Process A: TAK-117 600 mg, MTW QW | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
| Process A: TAK-117 900 mg, MTW QW | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
| Process B: TAK-117 900 mg FM MWF QW | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
| Process B: TAK-117 1200 mg FM MWF QW | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
| Process B: TAK-117 600 mg FM MTW QW | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
| Process B: TAK-117 900 mg FM MTW QW | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
| Process B: TAK-117 1200 mg FM MTW QW | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
| Process B: TAK-117 1500 mg FM MTW QW | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
| Process B: TAK-117 400 mg FM BID MWF QW | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
| Process B: TAK-117 500 mg FM BID MWF QW | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
| Process B: TAK-117 600 mg FM BID MWF QW | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 participants |
Primary
Number of Participants With Clinically Meaningful Changes in Laboratory Values
Time frame: Baseline up to Cycle 27 Day 45
Population: The ASat population included all enrolled participants who received at least 1 dose of TAK-117.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Process A: Total QD TAK-117 100-300 mg | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
| Process A: Total MWF QW 200-1200 mg | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
| Process A: Total MTW QW 200-900 mg | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
| Process B: Total FM MTW QW 600-1500 mg | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
| Process B: Total FM BID MWF QW 300-600 mg | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
| Process A: TAK-117 400 mg, MWF QW | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
| Process A: TAK-117 600 mg, MWF QW | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
| Process A: TAK-117 900 mg, MWF QW | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
| Process A: TAK-117 1200 mg, MWF QW | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
| Process A: TAK-117 200 mg, MTW QW | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
| Process A: TAK-117 400 mg, MTW QW | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
| Process A: TAK-117 600 mg, MTW QW | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
| Process A: TAK-117 900 mg, MTW QW | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
| Process B: TAK-117 900 mg FM MWF QW | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
| Process B: TAK-117 1200 mg FM MWF QW | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
| Process B: TAK-117 600 mg FM MTW QW | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
| Process B: TAK-117 900 mg FM MTW QW | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
| Process B: TAK-117 1200 mg FM MTW QW | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
| Process B: TAK-117 1500 mg FM MTW QW | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
| Process B: TAK-117 400 mg FM BID MWF QW | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
| Process B: TAK-117 500 mg FM BID MWF QW | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
| Process B: TAK-117 600 mg FM BID MWF QW | Number of Participants With Clinically Meaningful Changes in Laboratory Values | 0 participants |
Primary
Number of Participants With Clinically Meaningful Changes in Vital Signs
Time frame: Baseline up to Cycle 27 day 45
Population: The ASat population included all enrolled participants who received at least 1 dose of TAK-117.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Process A: Total QD TAK-117 100-300 mg | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
| Process A: Total MWF QW 200-1200 mg | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
| Process A: Total MTW QW 200-900 mg | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
| Process B: Total FM MTW QW 600-1500 mg | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
| Process B: Total FM BID MWF QW 300-600 mg | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
| Process A: TAK-117 400 mg, MWF QW | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
| Process A: TAK-117 600 mg, MWF QW | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
| Process A: TAK-117 900 mg, MWF QW | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
| Process A: TAK-117 1200 mg, MWF QW | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
| Process A: TAK-117 200 mg, MTW QW | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
| Process A: TAK-117 400 mg, MTW QW | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
| Process A: TAK-117 600 mg, MTW QW | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
| Process A: TAK-117 900 mg, MTW QW | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
| Process B: TAK-117 900 mg FM MWF QW | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
| Process B: TAK-117 1200 mg FM MWF QW | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
| Process B: TAK-117 600 mg FM MTW QW | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
| Process B: TAK-117 900 mg FM MTW QW | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
| Process B: TAK-117 1200 mg FM MTW QW | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
| Process B: TAK-117 1500 mg FM MTW QW | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
| Process B: TAK-117 400 mg FM BID MWF QW | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
| Process B: TAK-117 500 mg FM BID MWF QW | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
| Process B: TAK-117 600 mg FM BID MWF QW | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 participants |
Primary
Number of Participants With Highest Level of TEAEs Severity
Severity of AEs was evaluated based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0 as follow: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); Grade 4 (life-threatening); Grade 5 (fatal).
Time frame: Baseline up to Cycle 27 Day 45
Population: The ASat population included all enrolled participants who received at least 1 dose of TAK-117.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Process A: Total QD TAK-117 100-300 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 1 participants |
| Process A: Total QD TAK-117 100-300 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 3 participants |
| Process A: Total QD TAK-117 100-300 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 2 participants |
| Process A: Total QD TAK-117 100-300 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 0 participants |
| Process A: Total QD TAK-117 100-300 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 0 participants |
| Process A: Total MWF QW 200-1200 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 0 participants |
| Process A: Total MWF QW 200-1200 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 0 participants |
| Process A: Total MWF QW 200-1200 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 1 participants |
| Process A: Total MWF QW 200-1200 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 4 participants |
| Process A: Total MWF QW 200-1200 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 1 participants |
| Process A: Total MTW QW 200-900 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 3 participants |
| Process A: Total MTW QW 200-900 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 2 participants |
| Process A: Total MTW QW 200-900 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 0 participants |
| Process A: Total MTW QW 200-900 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 1 participants |
| Process A: Total MTW QW 200-900 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 2 participants |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 0 participants |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 1 participants |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 2 participants |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 0 participants |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 1 participants |
| Process B: Total FM MTW QW 600-1500 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 0 participants |
| Process B: Total FM MTW QW 600-1500 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 2 participants |
| Process B: Total FM MTW QW 600-1500 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 1 participants |
| Process B: Total FM MTW QW 600-1500 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 0 participants |
| Process B: Total FM MTW QW 600-1500 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 0 participants |
| Process B: Total FM BID MWF QW 300-600 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 2 participants |
| Process B: Total FM BID MWF QW 300-600 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 1 participants |
| Process B: Total FM BID MWF QW 300-600 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 0 participants |
| Process B: Total FM BID MWF QW 300-600 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 0 participants |
| Process B: Total FM BID MWF QW 300-600 mg | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 0 participants |
| Process A: TAK-117 400 mg, MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 0 participants |
| Process A: TAK-117 400 mg, MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 1 participants |
| Process A: TAK-117 400 mg, MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 2 participants |
| Process A: TAK-117 400 mg, MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 0 participants |
| Process A: TAK-117 400 mg, MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 0 participants |
| Process A: TAK-117 600 mg, MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 0 participants |
| Process A: TAK-117 600 mg, MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 2 participants |
| Process A: TAK-117 600 mg, MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 0 participants |
| Process A: TAK-117 600 mg, MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 0 participants |
| Process A: TAK-117 600 mg, MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 1 participants |
| Process A: TAK-117 900 mg, MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 5 participants |
| Process A: TAK-117 900 mg, MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 0 participants |
| Process A: TAK-117 900 mg, MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 1 participants |
| Process A: TAK-117 900 mg, MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 5 participants |
| Process A: TAK-117 900 mg, MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 1 participants |
| Process A: TAK-117 1200 mg, MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 0 participants |
| Process A: TAK-117 1200 mg, MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 0 participants |
| Process A: TAK-117 1200 mg, MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 0 participants |
| Process A: TAK-117 1200 mg, MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 3 participants |
| Process A: TAK-117 1200 mg, MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 0 participants |
| Process A: TAK-117 200 mg, MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 0 participants |
| Process A: TAK-117 200 mg, MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 1 participants |
| Process A: TAK-117 200 mg, MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 0 participants |
| Process A: TAK-117 200 mg, MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 0 participants |
| Process A: TAK-117 200 mg, MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 2 participants |
| Process A: TAK-117 400 mg, MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 0 participants |
| Process A: TAK-117 400 mg, MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 0 participants |
| Process A: TAK-117 400 mg, MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 1 participants |
| Process A: TAK-117 400 mg, MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 0 participants |
| Process A: TAK-117 400 mg, MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 2 participants |
| Process A: TAK-117 600 mg, MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 0 participants |
| Process A: TAK-117 600 mg, MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 0 participants |
| Process A: TAK-117 600 mg, MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 2 participants |
| Process A: TAK-117 600 mg, MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 1 participants |
| Process A: TAK-117 600 mg, MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 0 participants |
| Process A: TAK-117 900 mg, MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 0 participants |
| Process A: TAK-117 900 mg, MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 1 participants |
| Process A: TAK-117 900 mg, MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 7 participants |
| Process A: TAK-117 900 mg, MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 3 participants |
| Process A: TAK-117 900 mg, MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 0 participants |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 1 participants |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 1 participants |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 1 participants |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 0 participants |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 0 participants |
| Process B: TAK-117 900 mg FM MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 0 participants |
| Process B: TAK-117 900 mg FM MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 0 participants |
| Process B: TAK-117 900 mg FM MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 1 participants |
| Process B: TAK-117 900 mg FM MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 1 participants |
| Process B: TAK-117 900 mg FM MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 1 participants |
| Process B: TAK-117 1200 mg FM MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 1 participants |
| Process B: TAK-117 1200 mg FM MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 3 participants |
| Process B: TAK-117 1200 mg FM MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 0 participants |
| Process B: TAK-117 1200 mg FM MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 0 participants |
| Process B: TAK-117 1200 mg FM MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 3 participants |
| Process B: TAK-117 600 mg FM MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 3 participants |
| Process B: TAK-117 600 mg FM MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 0 participants |
| Process B: TAK-117 600 mg FM MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 0 participants |
| Process B: TAK-117 600 mg FM MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 0 participants |
| Process B: TAK-117 600 mg FM MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 0 participants |
| Process B: TAK-117 900 mg FM MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 0 participants |
| Process B: TAK-117 900 mg FM MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 2 participants |
| Process B: TAK-117 900 mg FM MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 0 participants |
| Process B: TAK-117 900 mg FM MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 0 participants |
| Process B: TAK-117 900 mg FM MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 1 participants |
| Process B: TAK-117 1200 mg FM MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 0 participants |
| Process B: TAK-117 1200 mg FM MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 1 participants |
| Process B: TAK-117 1200 mg FM MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 1 participants |
| Process B: TAK-117 1200 mg FM MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 1 participants |
| Process B: TAK-117 1200 mg FM MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 0 participants |
| Process B: TAK-117 1500 mg FM MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 0 participants |
| Process B: TAK-117 1500 mg FM MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 0 participants |
| Process B: TAK-117 1500 mg FM MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 0 participants |
| Process B: TAK-117 1500 mg FM MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 3 participants |
| Process B: TAK-117 1500 mg FM MTW QW | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 3 participants |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 0 participants |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 0 participants |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 1 participants |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 1 participants |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 1 participants |
| Process B: TAK-117 400 mg FM BID MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 0 participants |
| Process B: TAK-117 400 mg FM BID MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 0 participants |
| Process B: TAK-117 400 mg FM BID MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 1 participants |
| Process B: TAK-117 400 mg FM BID MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 1 participants |
| Process B: TAK-117 400 mg FM BID MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 2 participants |
| Process B: TAK-117 500 mg FM BID MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 4 participants |
| Process B: TAK-117 500 mg FM BID MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 0 participants |
| Process B: TAK-117 500 mg FM BID MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 0 participants |
| Process B: TAK-117 500 mg FM BID MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 3 participants |
| Process B: TAK-117 500 mg FM BID MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 3 participants |
| Process B: TAK-117 600 mg FM BID MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 1 | 0 participants |
| Process B: TAK-117 600 mg FM BID MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 4 | 1 participants |
| Process B: TAK-117 600 mg FM BID MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 5 | 1 participants |
| Process B: TAK-117 600 mg FM BID MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 2 | 1 participants |
| Process B: TAK-117 600 mg FM BID MWF QW | Number of Participants With Highest Level of TEAEs Severity | Grade 3 | 4 participants |
Secondary
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117
Time frame: Process A: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 24 hrs) post-dose; Process B: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 48 hrs) post-dose
Population: PK population included all participants who took at least 1 dose of study drug and had sufficient concentration-time data to calculate PK parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Process A: Total QD TAK-117 100-300 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117 | 18008 nanogram hours per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 78.8 |
| Process A: Total MWF QW 200-1200 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117 | 13807 nanogram hours per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 93.2 |
| Process A: Total MTW QW 200-900 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117 | 44733 nanogram hours per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 58 |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117 | 42909 nanogram hours per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 102.2 |
| Process B: Total FM MTW QW 600-1500 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117 | 93748 nanogram hours per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 19.8 |
| Process B: Total FM BID MWF QW 300-600 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117 | 75937 nanogram hours per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 94.4 |
| Process A: TAK-117 400 mg, MWF QW | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117 | 129217 nanogram hours per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 56 |
| Process A: TAK-117 600 mg, MWF QW | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117 | 309073 nanogram hours per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 23.7 |
| Process A: TAK-117 900 mg, MWF QW | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117 | NA nanogram hours per milliliter (ng*hr/mL) | — |
| Process A: TAK-117 1200 mg, MWF QW | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117 | NA nanogram hours per milliliter (ng*hr/mL) | — |
| Process A: TAK-117 200 mg, MTW QW | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117 | NA nanogram hours per milliliter (ng*hr/mL) | — |
| Process A: TAK-117 400 mg, MTW QW | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117 | 62876 nanogram hours per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 78.4 |
| Process A: TAK-117 600 mg, MTW QW | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117 | 84394 nanogram hours per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 103.1 |
| Process A: TAK-117 900 mg, MTW QW | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117 | 164508 nanogram hours per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 74.9 |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117 | 87515 nanogram hours per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 81.2 |
Secondary
%AUC Extrapolated: Percentage of Area Under Concentration-extrapolated
Time frame: Process A: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 24 hrs) post-dose; Process B: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 48 hrs) post-dose
Population: No data is reported since serum concentration of TAK-117 were below the limit of quantification.
Secondary
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-117
Time frame: Process A: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 24 hrs) post-dose; Process B: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 48 hrs) post-dose
Population: No data is reported since serum concentration of TAK-117 were below the limit of quantification.
Secondary
Clinical Benefit Rate (CBR)
Clinical benefit rate was defined as the participants who achieved stable disease (SD) for at least 15 weeks, CR, or PR. The estimate of the CBR was calculated as crude percentage of participants whose best ORR was CR, PR or SD for at least 90 days.
Time frame: Cycle 1 Day 8 up to Cycle 27 Day 1 or disease progression or death
Population: The FAS population included participants who received at least 1 dose of TAK-117, baseline data for those analyses that required baseline data and postbaseline endpoint data subsequent to at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Process A: Total QD TAK-117 100-300 mg | Clinical Benefit Rate (CBR) | 25 percentage of participants |
| Process A: Total MWF QW 200-1200 mg | Clinical Benefit Rate (CBR) | 17 percentage of participants |
| Process A: Total MTW QW 200-900 mg | Clinical Benefit Rate (CBR) | 38 percentage of participants |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Clinical Benefit Rate (CBR) | 100 percentage of participants |
| Process B: Total FM MTW QW 600-1500 mg | Clinical Benefit Rate (CBR) | 33 percentage of participants |
| Process B: Total FM BID MWF QW 300-600 mg | Clinical Benefit Rate (CBR) | 33 percentage of participants |
| Process A: TAK-117 400 mg, MWF QW | Clinical Benefit Rate (CBR) | 33 percentage of participants |
| Process A: TAK-117 600 mg, MWF QW | Clinical Benefit Rate (CBR) | 0 percentage of participants |
| Process A: TAK-117 900 mg, MWF QW | Clinical Benefit Rate (CBR) | 20 percentage of participants |
| Process A: TAK-117 1200 mg, MWF QW | Clinical Benefit Rate (CBR) | 67 percentage of participants |
| Process A: TAK-117 200 mg, MTW QW | Clinical Benefit Rate (CBR) | 0 percentage of participants |
| Process A: TAK-117 400 mg, MTW QW | Clinical Benefit Rate (CBR) | 0 percentage of participants |
| Process A: TAK-117 600 mg, MTW QW | Clinical Benefit Rate (CBR) | 0 percentage of participants |
| Process A: TAK-117 900 mg, MTW QW | Clinical Benefit Rate (CBR) | 56 percentage of participants |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Clinical Benefit Rate (CBR) | 33 percentage of participants |
| Process B: TAK-117 900 mg FM MWF QW | Clinical Benefit Rate (CBR) | 0 percentage of participants |
| Process B: TAK-117 1200 mg FM MWF QW | Clinical Benefit Rate (CBR) | 0 percentage of participants |
| Process B: TAK-117 600 mg FM MTW QW | Clinical Benefit Rate (CBR) | 33 percentage of participants |
| Process B: TAK-117 900 mg FM MTW QW | Clinical Benefit Rate (CBR) | 0 percentage of participants |
| Process B: TAK-117 1200 mg FM MTW QW | Clinical Benefit Rate (CBR) | 0 percentage of participants |
| Process B: TAK-117 1500 mg FM MTW QW | Clinical Benefit Rate (CBR) | 0 percentage of participants |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Clinical Benefit Rate (CBR) | 0 percentage of participants |
| Process B: TAK-117 400 mg FM BID MWF QW | Clinical Benefit Rate (CBR) | 33 percentage of participants |
| Process B: TAK-117 500 mg FM BID MWF QW | Clinical Benefit Rate (CBR) | 25 percentage of participants |
| Process B: TAK-117 600 mg FM BID MWF QW | Clinical Benefit Rate (CBR) | 25 percentage of participants |
Secondary
Cmax: Maximum Observed Plasma Concentration for TAK-117
Time frame: Process A: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 24 hrs) post-dose; Process B: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 48 hrs) post-dose
Population: Pharmacokinetic (PK) population included all participants who took at least 1 dose of study drug and had sufficient plasma concentration-time data to calculate PK parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Process A: Total QD TAK-117 100-300 mg | Cmax: Maximum Observed Plasma Concentration for TAK-117 | 1747.61 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 48.7 |
| Process A: Total MWF QW 200-1200 mg | Cmax: Maximum Observed Plasma Concentration for TAK-117 | 1613.23 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 58.5 |
| Process A: Total MTW QW 200-900 mg | Cmax: Maximum Observed Plasma Concentration for TAK-117 | 2736.60 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 36.4 |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Cmax: Maximum Observed Plasma Concentration for TAK-117 | 2658.23 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 90 |
| Process B: Total FM MTW QW 600-1500 mg | Cmax: Maximum Observed Plasma Concentration for TAK-117 | 4335.88 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 42.5 |
| Process B: Total FM BID MWF QW 300-600 mg | Cmax: Maximum Observed Plasma Concentration for TAK-117 | 4175.13 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 82.4 |
| Process A: TAK-117 400 mg, MWF QW | Cmax: Maximum Observed Plasma Concentration for TAK-117 | 7863.36 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 42.1 |
| Process A: TAK-117 600 mg, MWF QW | Cmax: Maximum Observed Plasma Concentration for TAK-117 | 8586.50 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 53.6 |
| Process A: TAK-117 900 mg, MWF QW | Cmax: Maximum Observed Plasma Concentration for TAK-117 | 1162.06 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 117.5 |
| Process A: TAK-117 1200 mg, MWF QW | Cmax: Maximum Observed Plasma Concentration for TAK-117 | 1656.71 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 77 |
| Process A: TAK-117 200 mg, MTW QW | Cmax: Maximum Observed Plasma Concentration for TAK-117 | 2973.26 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 53.3 |
| Process A: TAK-117 400 mg, MTW QW | Cmax: Maximum Observed Plasma Concentration for TAK-117 | 3870.43 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 61.1 |
| Process A: TAK-117 600 mg, MTW QW | Cmax: Maximum Observed Plasma Concentration for TAK-117 | 6960.06 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 69.3 |
| Process A: TAK-117 900 mg, MTW QW | Cmax: Maximum Observed Plasma Concentration for TAK-117 | 6073.55 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 53.2 |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Cmax: Maximum Observed Plasma Concentration for TAK-117 | 6899.80 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 67.9 |
Secondary
Ctrough: Observed Concentration at the End of Dosing Interval for TAK-117
Time frame: Process A: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 24 hrs) post-dose; Process B: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 48 hrs) post-dose
Population: PK population included all participants who took at least 1 dose of study drug and had sufficient concentration-time data to calculate PK parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Process A: Total QD TAK-117 100-300 mg | Ctrough: Observed Concentration at the End of Dosing Interval for TAK-117 | 187.29 ng/mL | Geometric Coefficient of Variation 102.1 |
| Process A: Total MWF QW 200-1200 mg | Ctrough: Observed Concentration at the End of Dosing Interval for TAK-117 | 177.70 ng/mL | Geometric Coefficient of Variation 124 |
| Process A: Total MTW QW 200-900 mg | Ctrough: Observed Concentration at the End of Dosing Interval for TAK-117 | 630.82 ng/mL | Geometric Coefficient of Variation 70 |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Ctrough: Observed Concentration at the End of Dosing Interval for TAK-117 | 627.62 ng/mL | Geometric Coefficient of Variation 93.7 |
| Process B: Total FM MTW QW 600-1500 mg | Ctrough: Observed Concentration at the End of Dosing Interval for TAK-117 | NA ng/mL | — |
| Process B: Total FM BID MWF QW 300-600 mg | Ctrough: Observed Concentration at the End of Dosing Interval for TAK-117 | NA ng/mL | — |
| Process A: TAK-117 400 mg, MWF QW | Ctrough: Observed Concentration at the End of Dosing Interval for TAK-117 | NA ng/mL | — |
| Process A: TAK-117 600 mg, MWF QW | Ctrough: Observed Concentration at the End of Dosing Interval for TAK-117 | NA ng/mL | — |
| Process A: TAK-117 900 mg, MWF QW | Ctrough: Observed Concentration at the End of Dosing Interval for TAK-117 | NA ng/mL | — |
| Process A: TAK-117 1200 mg, MWF QW | Ctrough: Observed Concentration at the End of Dosing Interval for TAK-117 | NA ng/mL | — |
| Process A: TAK-117 200 mg, MTW QW | Ctrough: Observed Concentration at the End of Dosing Interval for TAK-117 | NA ng/mL | — |
| Process A: TAK-117 400 mg, MTW QW | Ctrough: Observed Concentration at the End of Dosing Interval for TAK-117 | NA ng/mL | — |
| Process A: TAK-117 600 mg, MTW QW | Ctrough: Observed Concentration at the End of Dosing Interval for TAK-117 | NA ng/mL | — |
| Process A: TAK-117 900 mg, MTW QW | Ctrough: Observed Concentration at the End of Dosing Interval for TAK-117 | NA ng/mL | — |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Ctrough: Observed Concentration at the End of Dosing Interval for TAK-117 | NA ng/mL | — |
Secondary
Duration of Objective Response
Duration of response was to be calculated for participants who achieved CR or PR. Duration of objective response was defined as the number of days from the start date of PR or CR (whichever response was achieved first) to the first date that PD or disease progression was objectively documented. The duration of objective response was to be right-censored for participants who achieved CR or PR and met 1 of the following conditions: Non-protocol anticancer treatment started before documentation of PD; Documented PD after more than 1 missed disease assessment visit; Alive and did not have documentation of PD before a data analysis cutoff date.
Time frame: Cycle 1 Day 8 up to Cycle 27 Day 1 or disease progression or death
Population: The duration of objective response analysis was not performed due to change in planned analysis.
Secondary
Overall Response Rate (ORR)
The estimate of the ORR is calculated as crude percentage of participants who's best overall response is complete response (CR) or partial response (PR). Objective response (CR and PR) as determined by the participants best tumor response was assessed using response evaluation criteria in solid tumors (RECIST) version 1.1. As per RECIST version 1.1, CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 millimeter \[mm\]). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. Stable disease was defined as not qualifying for CR, PR, and progressive disease (PD).
Time frame: Cycle 1 Day 8 up to Cycle 27 Day 1 or disease progression or death
Population: The full analysis set (FAS) population included participants who received at least 1 dose of TAK-117, baseline data for those analyses that required baseline data and postbaseline endpoint data subsequent to at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Process A: Total QD TAK-117 100-300 mg | Overall Response Rate (ORR) | 0 percentage of participants |
| Process A: Total MWF QW 200-1200 mg | Overall Response Rate (ORR) | 0 percentage of participants |
| Process A: Total MTW QW 200-900 mg | Overall Response Rate (ORR) | 13 percentage of participants |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Overall Response Rate (ORR) | 100 percentage of participants |
| Process B: Total FM MTW QW 600-1500 mg | Overall Response Rate (ORR) | 0 percentage of participants |
| Process B: Total FM BID MWF QW 300-600 mg | Overall Response Rate (ORR) | 0 percentage of participants |
| Process A: TAK-117 400 mg, MWF QW | Overall Response Rate (ORR) | 0 percentage of participants |
| Process A: TAK-117 600 mg, MWF QW | Overall Response Rate (ORR) | 0 percentage of participants |
| Process A: TAK-117 900 mg, MWF QW | Overall Response Rate (ORR) | 0 percentage of participants |
| Process A: TAK-117 1200 mg, MWF QW | Overall Response Rate (ORR) | 0 percentage of participants |
| Process A: TAK-117 200 mg, MTW QW | Overall Response Rate (ORR) | 0 percentage of participants |
| Process A: TAK-117 400 mg, MTW QW | Overall Response Rate (ORR) | 0 percentage of participants |
| Process A: TAK-117 600 mg, MTW QW | Overall Response Rate (ORR) | 0 percentage of participants |
| Process A: TAK-117 900 mg, MTW QW | Overall Response Rate (ORR) | 0 percentage of participants |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Overall Response Rate (ORR) | 0 percentage of participants |
| Process B: TAK-117 900 mg FM MWF QW | Overall Response Rate (ORR) | 0 percentage of participants |
| Process B: TAK-117 1200 mg FM MWF QW | Overall Response Rate (ORR) | 0 percentage of participants |
| Process B: TAK-117 600 mg FM MTW QW | Overall Response Rate (ORR) | 0 percentage of participants |
| Process B: TAK-117 900 mg FM MTW QW | Overall Response Rate (ORR) | 0 percentage of participants |
| Process B: TAK-117 1200 mg FM MTW QW | Overall Response Rate (ORR) | 0 percentage of participants |
| Process B: TAK-117 1500 mg FM MTW QW | Overall Response Rate (ORR) | 0 percentage of participants |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Overall Response Rate (ORR) | 0 percentage of participants |
| Process B: TAK-117 400 mg FM BID MWF QW | Overall Response Rate (ORR) | 0 percentage of participants |
| Process B: TAK-117 500 mg FM BID MWF QW | Overall Response Rate (ORR) | 0 percentage of participants |
| Process B: TAK-117 600 mg FM BID MWF QW | Overall Response Rate (ORR) | 25 percentage of participants |
Secondary
Percent Change From Baseline in Pharmacodynamic Markers
Pharmacodynamic markers included phosphorylated ribosomal protein S6 (PS6), phosphorylated eukaryotic initiation factor 4E-binding protein 1 (P4EBP1), phosphorylated N-myc downstream regulated gene 1 (PNDRG1), phosphorylated proline-rich AKT substrate of 40 kilodaltons (PPRAS40), and phosphorylated serine/threonine protein kinase AKT (PAKT). Analysis population (n) for each skin biopsy biomarker is as follow: P4EBP1 (n=6,6,6,2,2,0,0,0,0,1,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0); PAKT and PNDRG1 (n=6,6,7,2,2,0,0,0,0,1,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0); PPRAS40 (n= 6,0,6,2,2,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0); PS6 (n=6,6,7,2,2,0,0,0,0,1,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0).n for each tumor tissue biomarkers is as follow: P4EBP1, PAKT, PNDRG1, and PS6 (n=1,1,0,0,1,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0); PPRAS40 (n= 1,0,0,0,1,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0).
Time frame: Cycle 1 Day 8
Population: Asat population where baseline and post-baseline assessments were available. The ASat population included all enrolled participants who received at least 1 dose of TAK-117.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Process A: Total QD TAK-117 100-300 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | -27.94 percent change | Standard Deviation 56.666 |
| Process A: Total QD TAK-117 100-300 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | 200.00 percent change | — |
| Process A: Total QD TAK-117 100-300 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | 196.83 percent change | — |
| Process A: Total QD TAK-117 100-300 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | 236.00 percent change | — |
| Process A: Total QD TAK-117 100-300 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | 69.56 percent change | Standard Deviation 272.327 |
| Process A: Total QD TAK-117 100-300 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | 850.00 percent change | — |
| Process A: Total QD TAK-117 100-300 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | -9.82 percent change | Standard Deviation 15.138 |
| Process A: Total QD TAK-117 100-300 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | -11.59 percent change | Standard Deviation 33.833 |
| Process A: Total QD TAK-117 100-300 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | 134.69 percent change | — |
| Process A: Total QD TAK-117 100-300 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | -15.23 percent change | Standard Deviation 18.886 |
| Process A: Total MWF QW 200-1200 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | -25.05 percent change | Standard Deviation 15.883 |
| Process A: Total MWF QW 200-1200 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | -20.87 percent change | — |
| Process A: Total MWF QW 200-1200 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | 0.00 percent change | — |
| Process A: Total MWF QW 200-1200 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | -16.49 percent change | — |
| Process A: Total MWF QW 200-1200 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | -13.07 percent change | Standard Deviation 39.758 |
| Process A: Total MWF QW 200-1200 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | NA percent change | — |
| Process A: Total MWF QW 200-1200 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | 190.32 percent change | Standard Deviation 257.212 |
| Process A: Total MWF QW 200-1200 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | -0.11 percent change | Standard Deviation 35.915 |
| Process A: Total MWF QW 200-1200 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | NA percent change | — |
| Process A: Total MWF QW 200-1200 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | -97.56 percent change | — |
| Process A: Total MTW QW 200-900 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | NA percent change | — |
| Process A: Total MTW QW 200-900 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | -61.41 percent change | Standard Deviation 40.015 |
| Process A: Total MTW QW 200-900 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | NA percent change | — |
| Process A: Total MTW QW 200-900 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | NA percent change | — |
| Process A: Total MTW QW 200-900 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | -26.90 percent change | Standard Deviation 37.191 |
| Process A: Total MTW QW 200-900 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | NA percent change | — |
| Process A: Total MTW QW 200-900 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | NA percent change | — |
| Process A: Total MTW QW 200-900 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | -30.02 percent change | Standard Deviation 37.444 |
| Process A: Total MTW QW 200-900 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | -11.88 percent change | Standard Deviation 37.773 |
| Process A: Total MTW QW 200-900 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | -10.11 percent change | Standard Deviation 26.814 |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | -18.75 percent change | Standard Deviation 61.872 |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | NA percent change | — |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | NA percent change | — |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | NA percent change | — |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | 22.70 percent change | Standard Deviation 24.462 |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | -24.50 percent change | Standard Deviation 54.388 |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | NA percent change | — |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | -12.97 percent change | Standard Deviation 5.896 |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | NA percent change | — |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | -21.67 percent change | Standard Deviation 35.355 |
| Process B: Total FM MTW QW 600-1500 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | 9.54 percent change | Standard Deviation 19.146 |
| Process B: Total FM MTW QW 600-1500 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | 10.69 percent change | Standard Deviation 31.283 |
| Process B: Total FM MTW QW 600-1500 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | 134.29 percent change | — |
| Process B: Total FM MTW QW 600-1500 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | -44.83 percent change | — |
| Process B: Total FM MTW QW 600-1500 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | -14.17 percent change | Standard Deviation 8.25 |
| Process B: Total FM MTW QW 600-1500 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | 10.43 percent change | — |
| Process B: Total FM MTW QW 600-1500 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | 7.48 percent change | — |
| Process B: Total FM MTW QW 600-1500 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | -18.75 percent change | Standard Deviation 26.517 |
| Process B: Total FM MTW QW 600-1500 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | -82.86 percent change | — |
| Process B: Total FM MTW QW 600-1500 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | -100.00 percent change | Standard Deviation 0 |
| Process B: Total FM BID MWF QW 300-600 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | NA percent change | — |
| Process B: Total FM BID MWF QW 300-600 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | NA percent change | — |
| Process B: Total FM BID MWF QW 300-600 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | NA percent change | — |
| Process B: Total FM BID MWF QW 300-600 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | NA percent change | — |
| Process B: Total FM BID MWF QW 300-600 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | NA percent change | — |
| Process B: Total FM BID MWF QW 300-600 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | NA percent change | — |
| Process B: Total FM BID MWF QW 300-600 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | NA percent change | — |
| Process B: Total FM BID MWF QW 300-600 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | NA percent change | — |
| Process B: Total FM BID MWF QW 300-600 mg | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | NA percent change | — |
| Process B: Total FM BID MWF QW 300-600 mg | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | NA percent change | — |
| Process A: TAK-117 400 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | NA percent change | — |
| Process A: TAK-117 400 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | NA percent change | — |
| Process A: TAK-117 400 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | NA percent change | — |
| Process A: TAK-117 400 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | NA percent change | — |
| Process A: TAK-117 400 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | NA percent change | — |
| Process A: TAK-117 400 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | NA percent change | — |
| Process A: TAK-117 400 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | NA percent change | — |
| Process A: TAK-117 400 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | NA percent change | — |
| Process A: TAK-117 400 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | NA percent change | — |
| Process A: TAK-117 400 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | NA percent change | — |
| Process A: TAK-117 600 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | NA percent change | — |
| Process A: TAK-117 600 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | NA percent change | — |
| Process A: TAK-117 600 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | NA percent change | — |
| Process A: TAK-117 600 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | NA percent change | — |
| Process A: TAK-117 600 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | NA percent change | — |
| Process A: TAK-117 600 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | NA percent change | — |
| Process A: TAK-117 600 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | NA percent change | — |
| Process A: TAK-117 600 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | NA percent change | — |
| Process A: TAK-117 600 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | NA percent change | — |
| Process A: TAK-117 600 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | NA percent change | — |
| Process A: TAK-117 900 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | NA percent change | — |
| Process A: TAK-117 900 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | NA percent change | — |
| Process A: TAK-117 900 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | NA percent change | — |
| Process A: TAK-117 900 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | NA percent change | — |
| Process A: TAK-117 900 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | NA percent change | — |
| Process A: TAK-117 900 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | NA percent change | — |
| Process A: TAK-117 900 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | NA percent change | — |
| Process A: TAK-117 900 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | NA percent change | — |
| Process A: TAK-117 900 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | NA percent change | — |
| Process A: TAK-117 900 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | NA percent change | — |
| Process A: TAK-117 1200 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | NA percent change | — |
| Process A: TAK-117 1200 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | NA percent change | — |
| Process A: TAK-117 1200 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | NA percent change | — |
| Process A: TAK-117 1200 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | -100.00 percent change | — |
| Process A: TAK-117 1200 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | 733.33 percent change | — |
| Process A: TAK-117 1200 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | NA percent change | — |
| Process A: TAK-117 1200 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | -34.44 percent change | — |
| Process A: TAK-117 1200 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | NA percent change | — |
| Process A: TAK-117 1200 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | 46.15 percent change | — |
| Process A: TAK-117 1200 mg, MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | NA percent change | — |
| Process A: TAK-117 200 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | NA percent change | — |
| Process A: TAK-117 200 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | NA percent change | — |
| Process A: TAK-117 200 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | NA percent change | — |
| Process A: TAK-117 200 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | NA percent change | — |
| Process A: TAK-117 200 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | NA percent change | — |
| Process A: TAK-117 200 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | NA percent change | — |
| Process A: TAK-117 200 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | NA percent change | — |
| Process A: TAK-117 200 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | NA percent change | — |
| Process A: TAK-117 200 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | NA percent change | — |
| Process A: TAK-117 200 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | NA percent change | — |
| Process A: TAK-117 400 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | NA percent change | — |
| Process A: TAK-117 400 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | NA percent change | — |
| Process A: TAK-117 400 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | NA percent change | — |
| Process A: TAK-117 400 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | NA percent change | — |
| Process A: TAK-117 400 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | NA percent change | — |
| Process A: TAK-117 400 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | NA percent change | — |
| Process A: TAK-117 400 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | NA percent change | — |
| Process A: TAK-117 400 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | NA percent change | — |
| Process A: TAK-117 400 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | NA percent change | — |
| Process A: TAK-117 400 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | NA percent change | — |
| Process A: TAK-117 600 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | NA percent change | — |
| Process A: TAK-117 600 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | NA percent change | — |
| Process A: TAK-117 600 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | NA percent change | — |
| Process A: TAK-117 600 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | NA percent change | — |
| Process A: TAK-117 600 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | NA percent change | — |
| Process A: TAK-117 600 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | NA percent change | — |
| Process A: TAK-117 600 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | NA percent change | — |
| Process A: TAK-117 600 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | NA percent change | — |
| Process A: TAK-117 600 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | NA percent change | — |
| Process A: TAK-117 600 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | NA percent change | — |
| Process A: TAK-117 900 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | NA percent change | — |
| Process A: TAK-117 900 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | NA percent change | — |
| Process A: TAK-117 900 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | NA percent change | — |
| Process A: TAK-117 900 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | NA percent change | — |
| Process A: TAK-117 900 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | NA percent change | — |
| Process A: TAK-117 900 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | NA percent change | — |
| Process A: TAK-117 900 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | NA percent change | — |
| Process A: TAK-117 900 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | NA percent change | — |
| Process A: TAK-117 900 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | NA percent change | — |
| Process A: TAK-117 900 mg, MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | NA percent change | — |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | NA percent change | — |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | NA percent change | — |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | NA percent change | — |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | NA percent change | — |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | NA percent change | — |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | NA percent change | — |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | NA percent change | — |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | NA percent change | — |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | NA percent change | — |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | NA percent change | — |
| Process B: TAK-117 900 mg FM MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | NA percent change | — |
| Process B: TAK-117 900 mg FM MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | NA percent change | — |
| Process B: TAK-117 900 mg FM MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | NA percent change | — |
| Process B: TAK-117 900 mg FM MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | NA percent change | — |
| Process B: TAK-117 900 mg FM MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | NA percent change | — |
| Process B: TAK-117 900 mg FM MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | NA percent change | — |
| Process B: TAK-117 900 mg FM MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | NA percent change | — |
| Process B: TAK-117 900 mg FM MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | NA percent change | — |
| Process B: TAK-117 900 mg FM MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | NA percent change | — |
| Process B: TAK-117 900 mg FM MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | NA percent change | — |
| Process B: TAK-117 1200 mg FM MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | NA percent change | — |
| Process B: TAK-117 1200 mg FM MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | NA percent change | — |
| Process B: TAK-117 1200 mg FM MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | NA percent change | — |
| Process B: TAK-117 1200 mg FM MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | NA percent change | — |
| Process B: TAK-117 1200 mg FM MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | NA percent change | — |
| Process B: TAK-117 1200 mg FM MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | NA percent change | — |
| Process B: TAK-117 1200 mg FM MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | NA percent change | — |
| Process B: TAK-117 1200 mg FM MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | NA percent change | — |
| Process B: TAK-117 1200 mg FM MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | NA percent change | — |
| Process B: TAK-117 1200 mg FM MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | NA percent change | — |
| Process B: TAK-117 600 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | NA percent change | — |
| Process B: TAK-117 600 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | NA percent change | — |
| Process B: TAK-117 600 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | NA percent change | — |
| Process B: TAK-117 600 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | NA percent change | — |
| Process B: TAK-117 600 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | NA percent change | — |
| Process B: TAK-117 600 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | NA percent change | — |
| Process B: TAK-117 600 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | NA percent change | — |
| Process B: TAK-117 600 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | NA percent change | — |
| Process B: TAK-117 600 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | NA percent change | — |
| Process B: TAK-117 600 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | NA percent change | — |
| Process B: TAK-117 900 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | NA percent change | — |
| Process B: TAK-117 900 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | NA percent change | — |
| Process B: TAK-117 900 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | NA percent change | — |
| Process B: TAK-117 900 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | NA percent change | — |
| Process B: TAK-117 900 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | NA percent change | — |
| Process B: TAK-117 900 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | NA percent change | — |
| Process B: TAK-117 900 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | NA percent change | — |
| Process B: TAK-117 900 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | NA percent change | — |
| Process B: TAK-117 900 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | NA percent change | — |
| Process B: TAK-117 900 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | NA percent change | — |
| Process B: TAK-117 1200 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | NA percent change | — |
| Process B: TAK-117 1200 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | NA percent change | — |
| Process B: TAK-117 1200 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | NA percent change | — |
| Process B: TAK-117 1200 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | NA percent change | — |
| Process B: TAK-117 1200 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | NA percent change | — |
| Process B: TAK-117 1200 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | NA percent change | — |
| Process B: TAK-117 1200 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | NA percent change | — |
| Process B: TAK-117 1200 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | NA percent change | — |
| Process B: TAK-117 1200 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | NA percent change | — |
| Process B: TAK-117 1200 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | NA percent change | — |
| Process B: TAK-117 1500 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | NA percent change | — |
| Process B: TAK-117 1500 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | NA percent change | — |
| Process B: TAK-117 1500 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | NA percent change | — |
| Process B: TAK-117 1500 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | NA percent change | — |
| Process B: TAK-117 1500 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | NA percent change | — |
| Process B: TAK-117 1500 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | NA percent change | — |
| Process B: TAK-117 1500 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | NA percent change | — |
| Process B: TAK-117 1500 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | NA percent change | — |
| Process B: TAK-117 1500 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | NA percent change | — |
| Process B: TAK-117 1500 mg FM MTW QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | NA percent change | — |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | NA percent change | — |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | NA percent change | — |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | NA percent change | — |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | NA percent change | — |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | NA percent change | — |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | NA percent change | — |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | NA percent change | — |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | NA percent change | — |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | NA percent change | — |
| Process B: TAK-117 300 mg FM Twice Daily (BID) MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | NA percent change | — |
| Process B: TAK-117 400 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | NA percent change | — |
| Process B: TAK-117 400 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | NA percent change | — |
| Process B: TAK-117 400 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | NA percent change | — |
| Process B: TAK-117 400 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | NA percent change | — |
| Process B: TAK-117 400 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | NA percent change | — |
| Process B: TAK-117 400 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | NA percent change | — |
| Process B: TAK-117 400 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | NA percent change | — |
| Process B: TAK-117 400 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | NA percent change | — |
| Process B: TAK-117 400 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | NA percent change | — |
| Process B: TAK-117 400 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | NA percent change | — |
| Process B: TAK-117 500 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | NA percent change | — |
| Process B: TAK-117 500 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | NA percent change | — |
| Process B: TAK-117 500 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | NA percent change | — |
| Process B: TAK-117 500 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | NA percent change | — |
| Process B: TAK-117 500 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | NA percent change | — |
| Process B: TAK-117 500 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | NA percent change | — |
| Process B: TAK-117 500 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | NA percent change | — |
| Process B: TAK-117 500 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | NA percent change | — |
| Process B: TAK-117 500 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | NA percent change | — |
| Process B: TAK-117 500 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | NA percent change | — |
| Process B: TAK-117 600 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PS6 | NA percent change | — |
| Process B: TAK-117 600 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PAKT | NA percent change | — |
| Process B: TAK-117 600 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PNDRG1 | NA percent change | — |
| Process B: TAK-117 600 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: P4EBP1 | NA percent change | — |
| Process B: TAK-117 600 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PPRAS40 | NA percent change | — |
| Process B: TAK-117 600 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PNDRG1 | NA percent change | — |
| Process B: TAK-117 600 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PAKT | NA percent change | — |
| Process B: TAK-117 600 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Tumor Tissue: PS6 | NA percent change | — |
| Process B: TAK-117 600 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: PPRAS40 | NA percent change | — |
| Process B: TAK-117 600 mg FM BID MWF QW | Percent Change From Baseline in Pharmacodynamic Markers | Skin Biopsy: P4EBP1 | NA percent change | — |
Secondary
T 1/2z: Terminal Disposition Phase Half-life for TAK-117
Time frame: Process A: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 24 hrs) post-dose; Process B: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 48 hrs) post-dose
Population: PK population included all participants who took at least 1 dose of study drug and had sufficient concentration-time data to calculate PK parameters.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Process A: Total QD TAK-117 100-300 mg | T 1/2z: Terminal Disposition Phase Half-life for TAK-117 | 8.74 hrs | Standard Deviation 3 |
| Process A: Total MWF QW 200-1200 mg | T 1/2z: Terminal Disposition Phase Half-life for TAK-117 | 7.32 hrs | Standard Deviation 3.3 |
| Process A: Total MTW QW 200-900 mg | T 1/2z: Terminal Disposition Phase Half-life for TAK-117 | 11.17 hrs | Standard Deviation 4.5 |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | T 1/2z: Terminal Disposition Phase Half-life for TAK-117 | 9.75 hrs | Standard Deviation 5.5 |
| Process B: Total FM MTW QW 600-1500 mg | T 1/2z: Terminal Disposition Phase Half-life for TAK-117 | 12.24 hrs | Standard Deviation 3.9 |
| Process B: Total FM BID MWF QW 300-600 mg | T 1/2z: Terminal Disposition Phase Half-life for TAK-117 | 14.71 hrs | Standard Deviation 6.4 |
| Process A: TAK-117 400 mg, MWF QW | T 1/2z: Terminal Disposition Phase Half-life for TAK-117 | 11.12 hrs | Standard Deviation 3.9 |
| Process A: TAK-117 600 mg, MWF QW | T 1/2z: Terminal Disposition Phase Half-life for TAK-117 | 25.87 hrs | Standard Deviation 22.7 |
| Process A: TAK-117 900 mg, MWF QW | T 1/2z: Terminal Disposition Phase Half-life for TAK-117 | NA hrs | — |
| Process A: TAK-117 1200 mg, MWF QW | T 1/2z: Terminal Disposition Phase Half-life for TAK-117 | NA hrs | — |
| Process A: TAK-117 200 mg, MTW QW | T 1/2z: Terminal Disposition Phase Half-life for TAK-117 | NA hrs | — |
| Process A: TAK-117 400 mg, MTW QW | T 1/2z: Terminal Disposition Phase Half-life for TAK-117 | 12.17 hrs | Standard Deviation 4 |
| Process A: TAK-117 600 mg, MTW QW | T 1/2z: Terminal Disposition Phase Half-life for TAK-117 | 8.34 hrs | Standard Deviation 4.7 |
| Process A: TAK-117 900 mg, MTW QW | T 1/2z: Terminal Disposition Phase Half-life for TAK-117 | 14.28 hrs | Standard Deviation 3.5 |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | T 1/2z: Terminal Disposition Phase Half-life for TAK-117 | 9.53 hrs | Standard Deviation 2.5 |
Secondary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117
Time frame: Process A: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 24 hrs) post-dose; Process B: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 48 hrs) post-dose
Population: PK population included all participants who took at least 1 dose of study drug and had sufficient concentration-time data to calculate PK parameters.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Process A: Total QD TAK-117 100-300 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117 | 1.5 hr |
| Process A: Total MWF QW 200-1200 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117 | 1.5 hr |
| Process A: Total MTW QW 200-900 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117 | 2.0 hr |
| Process B: Total FM MWF QW TAK-117 600-1200 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117 | 2.1 hr |
| Process B: Total FM MTW QW 600-1500 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117 | 4.0 hr |
| Process B: Total FM BID MWF QW 300-600 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117 | 3.1 hr |
| Process A: TAK-117 400 mg, MWF QW | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117 | 2.0 hr |
| Process A: TAK-117 600 mg, MWF QW | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117 | 5.8 hr |
| Process A: TAK-117 900 mg, MWF QW | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117 | 1.6 hr |
| Process A: TAK-117 1200 mg, MWF QW | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117 | 4.0 hr |
| Process A: TAK-117 200 mg, MTW QW | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117 | 3.6 hr |
| Process A: TAK-117 400 mg, MTW QW | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117 | 3.4 hr |
| Process A: TAK-117 600 mg, MTW QW | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117 | 4.0 hr |
| Process A: TAK-117 900 mg, MTW QW | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117 | 4.0 hr |
| Process B: TAK-117 600 mg Process B Capsule (FM) MWF QW | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117 | 3.8 hr |