Carcinoma, Non-small-cell Lung, Colorectal Cancer, Esophageal Neoplasms, Metastatic Pancreatic Cancer
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to confirm the safety and tolerability of TAK-931 in a cohort of Western participants with metastatic solid tumors and to evaluate the anti-tumor activity of TAK-931 in participants with metastatic pancreatic cancer, colorectal cancer (CRC), squamous esophageal cancer (sqEC), and squamous non-small-cell lung cancer (sqNSCLC).
Detailed description
Pancreatic Arm Now Closed. The drug being tested in this study is called TAK-931. TAK-931 blocks function of a specific protein called CDC7 kinase in the human body. TAK-931 is being tested in participants with metastatic cancer (colorectal, pancreatic, sqNSCLC and sqEC) in the United States and Japan and also in the participants with any type of metastatic cancer with no standard therapeutic alternative in the United States only. This study will look at the safety, tolerability and pharmacokinetics of TAK-931. The study will enroll approximately 160 participants. Participants will be enrolled in 5 cohorts: 1) Western safety cohort, to be enrolled in the United States only, will include non-Japanese participants with metastatic solid tumors and no standard therapeutic alternative, 2) Metastatic pancreatic cancer cohort, 3) Metastatic colorectal cancer cohort, 4) Metastatic sqNSCLC cohort, and 5) Metastatic sqEC cohort. All participants will receive: • TAK-931 50 mg (2x25 mg or 5x10 mg) capsules All participants will be asked to take one 50 mg (2x25 mg or 5x10 mg) capsule at the same time of the day every day for 14 days, followed by 7 days break in 21-day cycles throughout the study. This multi-center trial will be conducted in the United States and Japan. The overall time to participate in this study is approximately 24 months. Participants will make multiple visits to the clinic. Participants in both Western cohort and disease specific cohorts will be followed for progression-free survival every 12 weeks after the last dose of the study drug until the occurrence of disease progression, loss to follow up, consent withdrawal, death, start of subsequent antineoplastic therapy, study termination, or until 6 months after discontinuation of the study treatment, whichever occurs first. Once disease progression is confirmed, participants in the disease-specific cohorts will be followed for overall survival every 12 weeks until death, loss to follow up, consent withdrawal, study termination, or transfer of a participant to a long term safety study, single participant investigational new drug application, or similar program after the last dose of the study drug.
Interventions
DRUGTAK-931
TAK-931 hard gelatin capsules
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
1. Adult male or female participants aged \>=20 years (Japan) or \>=18 years (United States). 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 3. Has pathologically confirmed metastatic pancreatic adenocarcinoma that has progressed after, at least, a first line of standard systemic chemotherapy for the metastatic disease, OR participants with pathologically confirmed metastatic adenocarcinoma of the colon or rectum who have progressed to at least 2 lines of standard systemic chemotherapy for the metastatic disease, OR participants with pathologically confirmed locally advanced or metastatic sqEC that has progressed after at least a first line of standard systemic therapy for metastatic disease. First-line participants can be enrolled if a platinum doublet is contraindicated or refused by the participants, OR pathologically confirmed locally advanced or metastatic sqNSCLC that has progressed after at least 2 lines of standard systemic therapy for metastatic disease. 4. For the Western safety cohort only: participants with locally advanced or metastatic solid tumor for whom no standard treatment with an established survival benefit is available or if the participant refuses other standard therapy. 5. For disease-specific cohort participants: measurable disease per RECIST v. 1.1 6. Left ventricular ejection fraction greater than (\>) 50% as measured by ECHO or MUGA scan within 4 weeks before receiving the first dose of study drug. 7. Recovered to Grade 1 or baseline from all toxic effects of previous therapy (except alopecia or neuropathy). 8. Suitable venous access for the study-required blood sampling. 9. For the Western safety cohort only: willingness to undergo serial skin tissue biopsies. 10. For disease-specific cohort participants: Must have an archival (banked) tumor sample or agree to have a new (fresh) tumor biopsy during the screening period. If a new tumor sample is needed, the disease should be accessible for a nonsignificant risk biopsy procedure (those occurring outside the brain, lung/mediastinum, and pancreas, or obtained with endoscopic procedures not extending beyond the stomach or bowel). For participants in the Western safety cohort, this biopsy is optional.
Exclusion criteria
1. Participants who require continuous use of proton pump inhibitors (PPIs) or histamine-2 (H2) receptor antagonists and participants who are taking PPIs within 5 days before the first dose of study drug. 2. Treatment with clinically significant enzyme inducers, such as phenytoin, carbamazepine, phenobarbital, rifampin, rifabutin, rifapentine, or Saint John's wort within 14 days before the first dose of study drug. 3. Treatment with any systemic anticancer treatment (including investigational products) within 30 days or 5 half-lives, whichever is shorter, before the first dose of study drug. 4. History of any of the following within the last 3 months before administration of the first dose of study drug: * Ischemic myocardial event including angina requiring therapy and artery revascularization procedures, myocardial infarction, and unstable symptomatic ischemic heart disease. * Ischemic cerebrovascular event, including transient ischemic attack and artery, revascularization procedures. * Significant, uncontrolled cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation, or ventricular tachycardia). * New York Heart Association Class III to IV heart failure. * Any other cardiac condition that, in the opinion of the investigator, could pose an additional risk for participation in the study (example, pericardial effusion or restrictive cardiomyopathy). * Baseline prolongation of the QT interval corrected for heart rate (HR) using Fridericia's formula \[QT interval corrected for heart rate using Fridericia's formula (QTcF); example, repeated demonstration of QTcF interval \>480 millisecond (ms), history of congenital long QT syndrome, or torsades de pointes\]. 5. Hypertension that is unstable or not controlled by medication. 6. History of uncontrolled brain metastasis unless: * Previously treated with surgery, whole-brain radiation, or stereotactic radiosurgery, and * Stable disease (SD) for \>=30 days, without steroid use (or stable steroid dose established for \>=14 days before the first dose of TAK-931). 7. Known history of human immunodeficiency virus infection. 8. Known hepatitis B virus (HBV) surface antigen seropositive or detectable hepatitis C virus (HCV) infection viral load. Note: Participants who have positive HBV core antibody or HBV surface antigen antibody can be enrolled but must have an undetectable HBV viral load. 9. Prior treatment with radiation therapy involving \>=25% of the hematopoietically active bone marrow within 3 months before the first dose of study drug. 10. Participants with known microsatellite instability-high (MSI-H) genotype or known wild type tumor protein 53 (TP53) per local testing. 11. Western Safety Cohort Only: Participants with Japanese heredity.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Dose Limiting Toxicities (DLTs) in Western Safety Cohort | Cycle 1 (each cycle = 21 days) | DLT:Any following event related to TAK-931 assessed by Common Terminology Criteria for Adverse Events(CTCAE) version4.03;Non-febrile Grade 4 neutropenia; febrile neutropenia: Grade \>=3 neutropenia; Grade4 thrombocytopenia; Grade \>=3 thrombocytopenia of any duration accompanied by Grade 2 bleeding or requiring transfusion; delay in initiation of Cycle 2 by \>14 days due to lack of adequate recovery of treatment-related hematological or nonhematologic toxicities; Grade 2 ejection fraction decreased by echocardiogram(ECHO) or multiple gated acquisition(MUGA) scan; Grade 4 laboratory abnormalities; other Grade 2 nonhematologic toxicities considered by investigator to be related to study drug and dose-limiting; Participants receiving \<50% of doses (\<7 doses) of planned TAK-931 dosing in Cycle 1 due to study drug-related adverse events(AEs); Grade \>=3 nonhematologic toxicity with few exceptions: Grade 3 arthralgia/myalgia, fatigue, laboratory abnormalities, nausea and/or emesis or diarrhea. |
| Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading to Dose Modifications and TEAEs Leading to Treatment Discontinuation in Western Safety Cohort | From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) | An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an adverse event with an onset that occurred after receiving study drug. An SAE was any untoward medical occurrence or effect that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria. |
| Disease Control Rate (DCR) in Tumor-Specific Cohorts | From first dose up to end of treatment (Up to approximately 14 months) | DCR was defined as percentage of participants documented to have unconfirmed CR, PR, or SD for at least 6 weeks from treatment initiation according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as the best response. CR was defined as disappearance of all lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of lesions, taking as reference the baseline sum LD. Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started. PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-931 | Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose | — |
| AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931 | Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose | — |
| CLr: Renal Clearance of TAK-931 | Cycle 1 (each cycle = 21 days) Day 1 pre-dose and at multiple timepoints (up to 8 hours urine sampling) post-dose | CLr is a measure of apparent clearance of the drug from the plasma, renal clearance is a measure of drug excreted through kidneys/urine per unit time. |
| t1/2z: Terminal Disposition Phase Half-life for TAK-931 | Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose | — |
| CLss/F: Steady-state Apparent Oral Clearance for TAK-931 | Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose | CL/F was defined as apparent clearance of the drug from the plasma, calculated as the drug dose divided by AUC. |
| Overall Response Rate (CR and PR) | From first dose up to end of treatment (Up to approximately 14 months) | Overall response rate was defined as percentage of participants documented to have unconfirmed CR or PR according to RECIST v1.1 as the best response. CR was defined as disappearance of all lesions, PR was defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD. |
| Rac(AUC): Accumulation Ratio Based on AUC Over the Dosing Interval (AUCτ) for TAK-931 | Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose | — |
| Progression Free Survival (PFS) | From date of randomization until disease progression or death, whichever occurs first (Up to approximately 34 months) | PFS was defined as the time from the date of first dose to the date of first documentation of PD (including clinical progression or clinical deterioration) or death due to any cause, whichever occurs first. Per RECIST V1.1, PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. |
| Overall Survival (OS) in the Tumor-Specific Cohorts | Up to approximately 43 months | OS was defined as the time from the date of first dose of study drug to death due to any cause. |
| Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts | From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) | An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it did not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an adverse event with an onset that occurred after receiving study drug. TEAEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, where Grade 3: Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4:Life-threatening consequences, urgent intervention indicated; Grade 5:Death related to AE. An SAE was any untoward medical occurrence or effect that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria. |
| Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) | Clinical laboratory tests included hematology, clinical chemistry and urinalysis. The investigator determined if the results were clinically significant. Only those categories were reported which are clinically significant at post Baseline. |
| Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts | From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) | Vital signs included assessments of systolic and diastolic blood pressure (BP), heart rate (HR), and body temperature. The investigator determined if the results were clinically significant. Only those categories were reported which are clinically significant at post Baseline. |
| Duration of Response (DOR) | From first documented response until disease progression or end of treatment, whichever occurs first (Up to 14 months) | DOR was defined as the time from the date of first documentation of a CR or PR to the date of first documentation of tumor progression. Per RECIST V1.1, CR was defined as disappearance of all lesions, PR was defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD. PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. |
| Cmax: Maximum Observed Plasma Concentration for TAK-931 | Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose | — |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931 | Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose | — |
Countries
Japan, United States
Participant flow
Recruitment details
Participants took part in the study at 12 investigative sites in Japan and the United States from 25 October 2017 to 24 August 2020.
Pre-assignment details
The study had two parts, Part 1 (Safety Cohort) enrolled western participants with locally advanced/metastatic solid tumors to receive TAK-931 and assessed safety, tolerability and pharmacokinetics. In Part 2, participants were enrolled into Tumor (Disease)-Specific Cohorts based on tumor criteria: pancreatic cancer, metastatic colorectal cancer (CRC), squamous esophageal cancer (sqEC), squamous non-small-cell lung cancer (sqNSCLC) to receive TAK-931 and were assessed for antitumor activity.
Participants by arm
| Arm | Count |
|---|---|
| Western Safety Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort. | 12 |
| Pancreatic Cancer Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort. | 15 |
| Metastatic CRC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort. | 35 |
| sqEC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort. | 21 |
| sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort. | 18 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Death | 10 | 13 | 17 | 12 | 8 |
| Overall Study | Lost to Follow-up | 0 | 0 | 2 | 1 | 0 |
| Overall Study | Reason not Specified | 2 | 0 | 4 | 1 | 3 |
| Overall Study | Site Terminated by Sponsor | 0 | 0 | 4 | 7 | 5 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 3 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Western Safety Cohort | Pancreatic Cancer Cohort | sqNSCLC Cohort | sqEC Cohort | Metastatic CRC Cohort |
|---|---|---|---|---|---|---|
| Age, Continuous | 61.5 years STANDARD_DEVIATION 10.23 | 59.3 years STANDARD_DEVIATION 7.16 | 63.1 years STANDARD_DEVIATION 12.27 | 64.4 years STANDARD_DEVIATION 7.74 | 64.2 years STANDARD_DEVIATION 7.71 | 58.3 years STANDARD_DEVIATION 11.93 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 96 Participants | 11 Participants | 12 Participants | 18 Participants | 21 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 169.75 cm STANDARD_DEVIATION 10.513 | 172.47 cm STANDARD_DEVIATION 13.371 | 170.61 cm STANDARD_DEVIATION 11.596 | 172.26 cm STANDARD_DEVIATION 10.693 | 167.11 cm STANDARD_DEVIATION 7.975 | 168.64 cm STANDARD_DEVIATION 10.203 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 29 Participants | 0 Participants | 3 Participants | 2 Participants | 16 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 64 Participants | 9 Participants | 12 Participants | 15 Participants | 4 Participants | 24 Participants |
| Region of Enrollment Japan | 29 Participants | 0 Participants | 3 Participants | 2 Participants | 16 Participants | 8 Participants |
| Region of Enrollment United States | 72 Participants | 12 Participants | 12 Participants | 16 Participants | 5 Participants | 27 Participants |
| Sex: Female, Male Female | 40 Participants | 5 Participants | 5 Participants | 7 Participants | 4 Participants | 19 Participants |
| Sex: Female, Male Male | 61 Participants | 7 Participants | 10 Participants | 11 Participants | 17 Participants | 16 Participants |
| Smoking Classification Current Smoker | 10 Participants | 0 Participants | 0 Participants | 7 Participants | 3 Participants | 0 Participants |
| Smoking Classification Former Smoker | 26 Participants | 0 Participants | 0 Participants | 10 Participants | 16 Participants | 0 Participants |
| Smoking Classification Never Smoked | 65 Participants | 12 Participants | 15 Participants | 1 Participants | 2 Participants | 35 Participants |
| Substance Use Cigar | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Substance Use Cigarette | 21 Participants | 0 Participants | 0 Participants | 15 Participants | 6 Participants | 0 Participants |
| Substance Use Pipe | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Substance Use Tobacco | 15 Participants | 0 Participants | 0 Participants | 3 Participants | 12 Participants | 0 Participants |
| Weight | 73.87 kg STANDARD_DEVIATION 19.076 | 79.33 kg STANDARD_DEVIATION 16.052 | 73.22 kg STANDARD_DEVIATION 22.763 | 77.70 kg STANDARD_DEVIATION 18.77 | 57.07 kg STANDARD_DEVIATION 10.358 | 79.90 kg STANDARD_DEVIATION 17.457 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 10 / 12 | 13 / 15 | 17 / 35 | 12 / 21 | 8 / 18 |
| other Total, other adverse events | 5 / 12 | 8 / 15 | 27 / 35 | 14 / 21 | 14 / 18 |
| serious Total, serious adverse events | 7 / 12 | 6 / 15 | 8 / 35 | 5 / 21 | 3 / 18 |
Outcome results
Primary
Disease Control Rate (DCR) in Tumor-Specific Cohorts
DCR was defined as percentage of participants documented to have unconfirmed CR, PR, or SD for at least 6 weeks from treatment initiation according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as the best response. CR was defined as disappearance of all lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of lesions, taking as reference the baseline sum LD. Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started. PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: From first dose up to end of treatment (Up to approximately 14 months)
Population: Response-evaluable Analysis Set included all participants who received at least 1 dose of study drug, had measurable disease at Baseline, and had at least 1 post-baseline response assessment. As pre-specified in the protocol, this outcome measure evaluated and reported data for participants only in the Tumor-Specific Cohorts.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Western Safety Cohort | Disease Control Rate (DCR) in Tumor-Specific Cohorts | 46.2 percentage of participants |
| Metastatic CRC Cohort | Disease Control Rate (DCR) in Tumor-Specific Cohorts | 51.6 percentage of participants |
| sqEC Cohort | Disease Control Rate (DCR) in Tumor-Specific Cohorts | 52.6 percentage of participants |
| sqNSCLC Cohort | Disease Control Rate (DCR) in Tumor-Specific Cohorts | 58.8 percentage of participants |
Primary
Percentage of Participants With Dose Limiting Toxicities (DLTs) in Western Safety Cohort
DLT:Any following event related to TAK-931 assessed by Common Terminology Criteria for Adverse Events(CTCAE) version4.03;Non-febrile Grade 4 neutropenia; febrile neutropenia: Grade \>=3 neutropenia; Grade4 thrombocytopenia; Grade \>=3 thrombocytopenia of any duration accompanied by Grade 2 bleeding or requiring transfusion; delay in initiation of Cycle 2 by \>14 days due to lack of adequate recovery of treatment-related hematological or nonhematologic toxicities; Grade 2 ejection fraction decreased by echocardiogram(ECHO) or multiple gated acquisition(MUGA) scan; Grade 4 laboratory abnormalities; other Grade 2 nonhematologic toxicities considered by investigator to be related to study drug and dose-limiting; Participants receiving \<50% of doses (\<7 doses) of planned TAK-931 dosing in Cycle 1 due to study drug-related adverse events(AEs); Grade \>=3 nonhematologic toxicity with few exceptions: Grade 3 arthralgia/myalgia, fatigue, laboratory abnormalities, nausea and/or emesis or diarrhea.
Time frame: Cycle 1 (each cycle = 21 days)
Population: DLT-evaluable Analysis Set included all participants in the Western Safety Cohort who received at least 1 of their planned TAK-931 doses during their first cycle of treatment (unless interrupted by related AEs) and who had sufficient follow-up data to allow the investigators and sponsor to determine whether a DLT occurred. As pre-specified in the protocol, DLTs were collected only from participants in the Western Safety Cohort who were evaluable in DLT-evaluable Analysis Set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Western Safety Cohort | Percentage of Participants With Dose Limiting Toxicities (DLTs) in Western Safety Cohort | 50 percentage of participants |
Primary
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading to Dose Modifications and TEAEs Leading to Treatment Discontinuation in Western Safety Cohort
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an adverse event with an onset that occurred after receiving study drug. An SAE was any untoward medical occurrence or effect that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria.
Time frame: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)
Population: Safety Analysis Set included all participants who received any amount of study drug. As pre-specified in the protocol, this outcome measure reports data only in the participants with locally advanced or metastatic solid tumors in the Western Safety Cohort.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Western Safety Cohort | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading to Dose Modifications and TEAEs Leading to Treatment Discontinuation in Western Safety Cohort | TEAEs | 100 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading to Dose Modifications and TEAEs Leading to Treatment Discontinuation in Western Safety Cohort | SAEs | 58.3 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading to Dose Modifications and TEAEs Leading to Treatment Discontinuation in Western Safety Cohort | TEAEs Leading to Dose Modifications | 33.3 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading to Dose Modifications and TEAEs Leading to Treatment Discontinuation in Western Safety Cohort | TEAEs Leading to Treatment Discontinuation | 8.3 percentage of participants |
Secondary
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-931
Time frame: Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
Population: PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Number analyzed is the number of participants with data available for analysis at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Western Safety Cohort | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-931 | Cycle 1 Day 1 | 1190.22 h*ng/mL | Standard Deviation 540.877 |
| Western Safety Cohort | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-931 | Cycle 1 Day 8 | 1475.88 h*ng/mL | Standard Deviation 749.707 |
| Metastatic CRC Cohort | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-931 | Cycle 1 Day 1 | 1166.40 h*ng/mL | Standard Deviation 362.856 |
| Metastatic CRC Cohort | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-931 | Cycle 1 Day 8 | 1290.72 h*ng/mL | Standard Deviation 615.542 |
| sqEC Cohort | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-931 | Cycle 1 Day 1 | 1302.40 h*ng/mL | Standard Deviation 391.035 |
| sqEC Cohort | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-931 | Cycle 1 Day 8 | 1542.82 h*ng/mL | Standard Deviation 507.733 |
Secondary
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931
Time frame: Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
Population: PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Number analyzed is the number of participants with data available for analysis at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Western Safety Cohort | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931 | Cycle 1 Day 1 | 1165.52 h*ng/mL | Standard Deviation 552.287 |
| Western Safety Cohort | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931 | Cycle 1 Day 8 | 1426.70 h*ng/mL | Standard Deviation 774.257 |
| Metastatic CRC Cohort | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931 | Cycle 1 Day 1 | 1114.23 h*ng/mL | Standard Deviation 388.844 |
| Metastatic CRC Cohort | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931 | Cycle 1 Day 8 | 1289.33 h*ng/mL | Standard Deviation 616.737 |
| sqEC Cohort | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931 | Cycle 1 Day 1 | 1311.41 h*ng/mL | Standard Deviation 388.557 |
| sqEC Cohort | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931 | Cycle 1 Day 8 | 1551.57 h*ng/mL | Standard Deviation 497.856 |
Secondary
CLr: Renal Clearance of TAK-931
CLr is a measure of apparent clearance of the drug from the plasma, renal clearance is a measure of drug excreted through kidneys/urine per unit time.
Time frame: Cycle 1 (each cycle = 21 days) Day 1 pre-dose and at multiple timepoints (up to 8 hours urine sampling) post-dose
Population: PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for urine PK sampling was collected only for participants in Western Safety Cohort. Overall number of participants analyzed are the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Western Safety Cohort | CLr: Renal Clearance of TAK-931 | 2.16 L/h | Standard Deviation 1.913 |
Secondary
CLss/F: Steady-state Apparent Oral Clearance for TAK-931
CL/F was defined as apparent clearance of the drug from the plasma, calculated as the drug dose divided by AUC.
Time frame: Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
Population: PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Overall number of participants analyzed are the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Western Safety Cohort | CLss/F: Steady-state Apparent Oral Clearance for TAK-931 | 39.71 L/h | Standard Deviation 14.135 |
| Metastatic CRC Cohort | CLss/F: Steady-state Apparent Oral Clearance for TAK-931 | 45.58 L/h | Standard Deviation 18.877 |
| sqEC Cohort | CLss/F: Steady-state Apparent Oral Clearance for TAK-931 | 35.57 L/h | Standard Deviation 10.778 |
Secondary
Cmax: Maximum Observed Plasma Concentration for TAK-931
Time frame: Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
Population: Pharmacokinetic (PK) Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Number analyzed is the number of participants with data available for analysis at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Western Safety Cohort | Cmax: Maximum Observed Plasma Concentration for TAK-931 | Cycle 1 Day 1 | 173.61 ng/mL | Standard Deviation 59.677 |
| Western Safety Cohort | Cmax: Maximum Observed Plasma Concentration for TAK-931 | Cycle 1 Day 8 | 196.17 ng/mL | Standard Deviation 73.702 |
| Metastatic CRC Cohort | Cmax: Maximum Observed Plasma Concentration for TAK-931 | Cycle 1 Day 1 | 204.69 ng/mL | Standard Deviation 90.527 |
| Metastatic CRC Cohort | Cmax: Maximum Observed Plasma Concentration for TAK-931 | Cycle 1 Day 8 | 180.55 ng/mL | Standard Deviation 75.036 |
| sqEC Cohort | Cmax: Maximum Observed Plasma Concentration for TAK-931 | Cycle 1 Day 1 | 185.46 ng/mL | Standard Deviation 61.158 |
| sqEC Cohort | Cmax: Maximum Observed Plasma Concentration for TAK-931 | Cycle 1 Day 8 | 216.18 ng/mL | Standard Deviation 121.488 |
Secondary
Duration of Response (DOR)
DOR was defined as the time from the date of first documentation of a CR or PR to the date of first documentation of tumor progression. Per RECIST V1.1, CR was defined as disappearance of all lesions, PR was defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD. PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: From first documented response until disease progression or end of treatment, whichever occurs first (Up to 14 months)
Population: Response-evaluable Analysis Set included all participants who received at least 1 dose of study drug, had measurable disease at Baseline, and had at least 1 post-baseline response assessment. Only responders were to be analyzed for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Western Safety Cohort | Duration of Response (DOR) | NA months |
| sqNSCLC Cohort | Duration of Response (DOR) | NA months |
Secondary
Overall Response Rate (CR and PR)
Overall response rate was defined as percentage of participants documented to have unconfirmed CR or PR according to RECIST v1.1 as the best response. CR was defined as disappearance of all lesions, PR was defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD.
Time frame: From first dose up to end of treatment (Up to approximately 14 months)
Population: Response-evaluable Analysis Set included all participants who received at least 1 dose of study drug, had measurable disease at Baseline, and had at least 1 post-baseline response assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Western Safety Cohort | Overall Response Rate (CR and PR) | 8.3 percentage of participants |
| Metastatic CRC Cohort | Overall Response Rate (CR and PR) | 0 percentage of participants |
| sqEC Cohort | Overall Response Rate (CR and PR) | 0 percentage of participants |
| sqNSCLC Cohort | Overall Response Rate (CR and PR) | 5.3 percentage of participants |
| sqNSCLC Cohort | Overall Response Rate (CR and PR) | 0 percentage of participants |
Secondary
Overall Survival (OS) in the Tumor-Specific Cohorts
OS was defined as the time from the date of first dose of study drug to death due to any cause.
Time frame: Up to approximately 43 months
Population: Safety Analysis Set included all participants who received any amount of study drug. Participants without documentation of death at the time of analysis were censored at the date last known to be alive. As pre-specified in the protocol, this outcome measure evaluated and reported data for participants only in the Tumor-Specific Cohorts.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Western Safety Cohort | Overall Survival (OS) in the Tumor-Specific Cohorts | 4.67 months |
| Metastatic CRC Cohort | Overall Survival (OS) in the Tumor-Specific Cohorts | 7.72 months |
| sqEC Cohort | Overall Survival (OS) in the Tumor-Specific Cohorts | 8.61 months |
| sqNSCLC Cohort | Overall Survival (OS) in the Tumor-Specific Cohorts | NA months |
Secondary
Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts
Clinical laboratory tests included hematology, clinical chemistry and urinalysis. The investigator determined if the results were clinically significant. Only those categories were reported which are clinically significant at post Baseline.
Time frame: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)
Population: Safety Analysis Set included all participants who received any amount of study drug. As pre-specified in the protocol, this outcome measure evaluated and reported data for participants only in the Tumor-Specific Cohorts.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Glucose Increased | 6.7 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Sodium Decreased | 0 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Aspartate Aminotransferase Increased | 6.7 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Uric Acid Increased | 6.7 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Platelet Count Decreased | 0 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Neutrophil Count Decreased | 26.7 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Alkaline Phosphatase Increased | 6.7 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | White Blood Cell Count Decreased | 20.0 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Haematocrit Decreased | 6.7 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Alanine Aminotransferase Increased | 6.7 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Bilirubin Increased | 0 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Protein Total Decreased | 6.7 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Hepatic Enzyme Increased | 6.7 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Red Blood Cell Count Decreased | 6.7 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Creatinine Increased | 20.0 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Lymphocyte Count Decreased | 13.3 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Albumin Decreased | 6.7 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Creatinine Decreased | 6.7 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Urea Increased | 6.7 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Chloride Decreased | 6.7 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Glucose Increased | 0 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Chloride Decreased | 0 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Haematocrit Decreased | 0 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Uric Acid Increased | 0 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Bilirubin Increased | 2.9 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Sodium Decreased | 2.9 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Neutrophil Count Decreased | 17.1 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Red Blood Cell Count Decreased | 0 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Urea Increased | 0 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Platelet Count Decreased | 5.7 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Hepatic Enzyme Increased | 0 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Alkaline Phosphatase Increased | 5.7 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Creatinine Decreased | 0 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Aspartate Aminotransferase Increased | 2.9 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Albumin Decreased | 0 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Lymphocyte Count Decreased | 0 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Creatinine Increased | 0 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Alanine Aminotransferase Increased | 0 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | White Blood Cell Count Decreased | 8.6 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Protein Total Decreased | 0 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Platelet Count Decreased | 4.8 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Neutrophil Count Decreased | 38.1 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | White Blood Cell Count Decreased | 42.9 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Lymphocyte Count Decreased | 0 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Aspartate Aminotransferase Increased | 0 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Alanine Aminotransferase Increased | 0 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Bilirubin Increased | 0 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Hepatic Enzyme Increased | 0 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Creatinine Increased | 4.8 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Creatinine Decreased | 0 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Urea Increased | 0 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Chloride Decreased | 0 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Sodium Decreased | 0 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Alkaline Phosphatase Increased | 0 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Uric Acid Increased | 0 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Glucose Increased | 0 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Albumin Decreased | 0 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Protein Total Decreased | 0 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Haematocrit Decreased | 0 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Red Blood Cell Count Decreased | 0 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Urea Increased | 0 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Creatinine Decreased | 0 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Haematocrit Decreased | 0 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Glucose Increased | 0 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Creatinine Increased | 0 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Hepatic Enzyme Increased | 0 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | White Blood Cell Count Decreased | 5.6 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Albumin Decreased | 0 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Bilirubin Increased | 0 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Alanine Aminotransferase Increased | 5.6 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Neutrophil Count Decreased | 27.8 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Protein Total Decreased | 0 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Aspartate Aminotransferase Increased | 5.6 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Platelet Count Decreased | 0 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Lymphocyte Count Decreased | 5.6 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Alkaline Phosphatase Increased | 0 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Sodium Decreased | 0 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Chloride Decreased | 0 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Red Blood Cell Count Decreased | 0 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts | Blood Uric Acid Increased | 0 percentage of participants |
Secondary
Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts
Vital signs included assessments of systolic and diastolic blood pressure (BP), heart rate (HR), and body temperature. The investigator determined if the results were clinically significant. Only those categories were reported which are clinically significant at post Baseline.
Time frame: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)
Population: Safety Analysis Set included all participants who received any amount of study drug. As pre-specified in the protocol, this outcome measure evaluated and reported data for participants only in the Tumor-Specific Cohorts.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts | Atrial Fibrillation | 0 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts | Tachycardia | 0 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts | Increase in HR | 0 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts | Bradycardia | 0 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts | Orthostatic Hypotension | 0 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts | Bradycardia | 2.9 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts | Atrial Fibrillation | 2.9 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts | Increase in HR | 2.9 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts | Tachycardia | 5.7 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts | Orthostatic Hypotension | 2.9 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts | Bradycardia | 0 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts | Orthostatic Hypotension | 0 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts | Tachycardia | 0 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts | Atrial Fibrillation | 0 percentage of participants |
| sqEC Cohort | Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts | Increase in HR | 0 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts | Atrial Fibrillation | 0 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts | Tachycardia | 0 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts | Orthostatic Hypotension | 0 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts | Bradycardia | 0 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts | Increase in HR | 0 percentage of participants |
Secondary
Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it did not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an adverse event with an onset that occurred after receiving study drug. TEAEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, where Grade 3: Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4:Life-threatening consequences, urgent intervention indicated; Grade 5:Death related to AE. An SAE was any untoward medical occurrence or effect that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria.
Time frame: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)
Population: Safety Analysis Set included all participants who received any amount of study drug. As pre-specified in the protocol, this outcome measure evaluated and reported data for participants only in the Tumor-Specific Cohorts.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Western Safety Cohort | Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts | Grade >=3 TEAEs | 73.3 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts | SAEs | 40.0 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts | TEAEs Leading to Dose Modifications | 53.3 percentage of participants |
| Western Safety Cohort | Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts | TEAEs Leading to Treatment Discontinuation | 13.3 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts | SAEs | 22.9 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts | TEAEs Leading to Treatment Discontinuation | 8.6 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts | Grade >=3 TEAEs | 54.3 percentage of participants |
| Metastatic CRC Cohort | Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts | TEAEs Leading to Dose Modifications | 48.6 percentage of participants |
| sqEC Cohort | Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts | TEAEs Leading to Dose Modifications | 52.4 percentage of participants |
| sqEC Cohort | Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts | TEAEs Leading to Treatment Discontinuation | 9.5 percentage of participants |
| sqEC Cohort | Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts | Grade >=3 TEAEs | 57.1 percentage of participants |
| sqEC Cohort | Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts | SAEs | 23.8 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts | TEAEs Leading to Treatment Discontinuation | 0 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts | Grade >=3 TEAEs | 44.4 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts | SAEs | 16.7 percentage of participants |
| sqNSCLC Cohort | Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts | TEAEs Leading to Dose Modifications | 38.9 percentage of participants |
Secondary
Progression Free Survival (PFS)
PFS was defined as the time from the date of first dose to the date of first documentation of PD (including clinical progression or clinical deterioration) or death due to any cause, whichever occurs first. Per RECIST V1.1, PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: From date of randomization until disease progression or death, whichever occurs first (Up to approximately 34 months)
Population: Safety Analysis Set included all participants who received any amount of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Western Safety Cohort | Progression Free Survival (PFS) | 2.05 months |
| Metastatic CRC Cohort | Progression Free Survival (PFS) | 1.31 months |
| sqEC Cohort | Progression Free Survival (PFS) | 1.45 months |
| sqNSCLC Cohort | Progression Free Survival (PFS) | 3.02 months |
| sqNSCLC Cohort | Progression Free Survival (PFS) | 2.12 months |
Secondary
Rac(AUC): Accumulation Ratio Based on AUC Over the Dosing Interval (AUCτ) for TAK-931
Time frame: Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
Population: PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Overall number of participants analyzed are the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Western Safety Cohort | Rac(AUC): Accumulation Ratio Based on AUC Over the Dosing Interval (AUCτ) for TAK-931 | 1.27 ratio | Standard Deviation 0.317 |
| Metastatic CRC Cohort | Rac(AUC): Accumulation Ratio Based on AUC Over the Dosing Interval (AUCτ) for TAK-931 | 1.10 ratio | Standard Deviation 0.299 |
| sqEC Cohort | Rac(AUC): Accumulation Ratio Based on AUC Over the Dosing Interval (AUCτ) for TAK-931 | 1.12 ratio | Standard Deviation 0.203 |
Secondary
t1/2z: Terminal Disposition Phase Half-life for TAK-931
Time frame: Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
Population: PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Overall number of participants analyzed are the number of participants with data available for analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Western Safety Cohort | t1/2z: Terminal Disposition Phase Half-life for TAK-931 | 5.95 hour |
| Metastatic CRC Cohort | t1/2z: Terminal Disposition Phase Half-life for TAK-931 | 5.53 hour |
| sqEC Cohort | t1/2z: Terminal Disposition Phase Half-life for TAK-931 | 6.18 hour |
Secondary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931
Time frame: Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose
Population: PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Number analyzed is the number of participants with data available for analysis at the given timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Western Safety Cohort | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931 | Cycle 1 Day 1 | 1.57 hour |
| Western Safety Cohort | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931 | Cycle 1 Day 8 | 1.59 hour |
| Metastatic CRC Cohort | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931 | Cycle 1 Day 1 | 2.00 hour |
| Metastatic CRC Cohort | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931 | Cycle 1 Day 8 | 2.00 hour |
| sqEC Cohort | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931 | Cycle 1 Day 1 | 1.85 hour |
| sqEC Cohort | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931 | Cycle 1 Day 8 | 1.97 hour |