Trial Outcomes & Findings for Docetaxel With or Without TAK-117 (MLN1117) in Participants With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NCT NCT02393209)

Last Updated: 2018-02-07

Results Overview

DLT was evaluated according to National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 and was defined as any of the following events: 1. Grade 4 neutropenia or thrombocytopenia lasting ≥7 consecutive days; 2. Grade 4 neutropenia with fever and/or infection; 3. Platelet count \<10,000/mm\^3; 4. ≥Grade 3 thrombocytopenia with bleeding; 5. Any other ≥Grade 4 hematologic toxicity; 6. Any other ≥Grade 3 nonhematologic toxicity, with following exceptions: ≥Grade 3 arthralgia/myalgia, ≥Grade 3 nausea/emesis, ≥Grade 3 diarrhoea, Grade 3 fatigue, Grade 3 Rash, Grade 3 nonhematological toxicity that could be controlled to ≤Grade 1 with appropriate treatment; 7. Inability to administer at least 75% of planned doses; 8. Clinically significant occurrence per investigator that is a safety risk.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

14 participants

Primary outcome timeframe

Cycle 1 (Up to Day 21)

Results posted on

2018-02-07

Participant Flow

Participants took part in the study at 5 investigative sites in United States and 1 in Canada from 03 June 2015 to 20 January 2017. The Phase 2 portion of the study was cancelled by the sponsor.

Participants with a diagnosis of metastatic non-small lung cancer were enrolled in a dose escalation study and received one of 2 doses: TAK-117 (200 mg) plus docetaxel or TAK-117 (300 mg) plus docetaxel.

Participant milestones

Participant milestones
Measure	Phase 1 - TAK-117 200 mg + Docetaxel 36 mg/m^2 TAK-117 200 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, intravenous (IV) infusion, on Days 1 and 8 of the 21-day cycle up to 9 cycles (approximately 189 days).	Phase 1 - TAK-117 300 mg + Docetaxel 36 mg/m^2 TAK-117 300 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, IV infusion, on Days 1 and 8 of the 21-day cycle up to 6 cycles (approximately 126 days).
Overall Study STARTED	6	8
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	6	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1 - TAK-117 200 mg + Docetaxel 36 mg/m^2 TAK-117 200 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, intravenous (IV) infusion, on Days 1 and 8 of the 21-day cycle up to 9 cycles (approximately 189 days).	Phase 1 - TAK-117 300 mg + Docetaxel 36 mg/m^2 TAK-117 300 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, IV infusion, on Days 1 and 8 of the 21-day cycle up to 6 cycles (approximately 126 days).
Overall Study Study Terminated by Sponsor	1	1
Overall Study Withdrawal by Patient	1	0
Overall Study Death	2	2
Overall Study Death due to Disease Progression	2	2
Overall Study Death from Legionella Infection	0	1
Overall Study Patient Seen by Another Oncologist	0	1
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Docetaxel With or Without TAK-117 (MLN1117) in Participants With Locally Advanced or Metastatic Non-small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1 - TAK-117 200 mg + Docetaxel 36 mg/m^2 n=6 Participants TAK-117 200 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, intravenous (IV) infusion, on Days 1 and 8 of the 21-day cycle up to 9 cycles (approximately 189 days).	Phase 1 - TAK-117 300 mg + Docetaxel 36 mg/m^2 n=8 Participants TAK-117 300 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, IV infusion, on Days 1 and 8 of the 21-day cycle up to 6 cycles (approximately 126 days).	Total n=14 Participants Total of all reporting groups
Age, Continuous	64.0 years STANDARD_DEVIATION 8.10 • n=93 Participants	62.1 years STANDARD_DEVIATION 11.32 • n=4 Participants	62.9 years STANDARD_DEVIATION 9.75 • n=27 Participants
Sex: Female, Male Female	1 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants
Sex: Female, Male Male	5 Participants n=93 Participants	6 Participants n=4 Participants	11 Participants n=27 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	5 Participants n=93 Participants	7 Participants n=4 Participants	12 Participants n=27 Participants
Race/Ethnicity, Customized Not Reported	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized White	4 Participants n=93 Participants	5 Participants n=4 Participants	9 Participants n=27 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants
Race/Ethnicity, Customized Asian	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized Not reported	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Height	171.53 cm STANDARD_DEVIATION 5.854 • n=93 Participants	172.95 cm STANDARD_DEVIATION 6.102 • n=4 Participants	172.34 cm STANDARD_DEVIATION 5.810 • n=27 Participants
Weight	69.48 kg STANDARD_DEVIATION 21.630 • n=93 Participants	72.69 kg STANDARD_DEVIATION 9.157 • n=4 Participants	71.31 kg STANDARD_DEVIATION 15.093 • n=27 Participants
Body Surface Area	1.805 m^2 STANDARD_DEVIATION 0.2987 • n=93 Participants	1.865 m^2 STANDARD_DEVIATION 0.1231 • n=4 Participants	1.839 m^2 STANDARD_DEVIATION 0.2084 • n=27 Participants

PRIMARY outcome

Timeframe: Cycle 1 (Up to Day 21)

Population: The DLT-evaluable population was defined as all participants who either experienced DLT during Cycle 1 or complete treatment with at least 75% of the planned doses of TAK-117 plus docetaxel and have sufficient follow-up data to allow investigators and sponsor to determine whether DLT occurred.

Outcome measures

Outcome measures
Measure	Phase 1 - TAK-117 200 mg + Docetaxel 36 mg/m^2 n=6 Participants TAK-117 200 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, intravenous (IV) infusion, on Days 1 and 8 of the 21-day cycle up to 9 cycles (approximately 189 days).	Phase 1 - TAK-117 300 mg + Docetaxel 36 mg/m^2 n=8 Participants TAK-117 300 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, IV infusion, on Days 1 and 8 of the 21-day cycle up to 6 cycles (approximately 126 days).
Number of Participants With Dose-Limiting Toxicity (DLT) in Phase 1b	0 participants	1 participants

PRIMARY outcome

Timeframe: Cycle 1 (Up to Day 21)

The MTD is defined as the dose of TAK-117 in combination with docetaxel 36 mg/m\^2 at which 1 of 6 evaluable participants experience DLT. DLT was evaluated according to NCI CTCAE version 4.03 and was defined as any of the following events: 1. Grade 4 neutropenia or thrombocytopenia lasting ≥7 consecutive days; 2. Grade 4 neutropenia with fever and/or infection; 3. Platelet count \<10,000/mm\^3; 4. ≥Grade 3 thrombocytopenia with bleeding; 5. Any other ≥Grade 4 hematologic toxicity; 6. Any other ≥Grade 3 nonhematologic toxicity, with following exceptions: ≥Grade 3 arthralgia/myalgia, ≥Grade 3 nausea/emesis, ≥Grade 3 diarrhoea, Grade 3 fatigue, Grade 3 Rash, Grade 3 nonhematological toxicity that could be controlled to ≤Grade 1 with appropriate treatment; 7. Inability to administer at least 75% of planned doses; 8. Clinically significant occurrence per investigator that is a safety risk.

Outcome measures

Outcome measures
Measure	Phase 1 - TAK-117 200 mg + Docetaxel 36 mg/m^2 n=14 Participants TAK-117 200 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, intravenous (IV) infusion, on Days 1 and 8 of the 21-day cycle up to 9 cycles (approximately 189 days).	Phase 1 - TAK-117 300 mg + Docetaxel 36 mg/m^2 TAK-117 300 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, IV infusion, on Days 1 and 8 of the 21-day cycle up to 6 cycles (approximately 126 days).
Maximum Tolerated Dose (MTD) of TAK-117 in Combination With Docetaxel 36 mg/m^2 in Phase 1b	300 mg	—

PRIMARY outcome

Timeframe: Cycle 1 (Up to Day 21)

The recommended phase 2 dose was determined in Phase 1b based on participant dose-limiting toxicities and the maximum tolerated dose.

Outcome measures

Outcome measures
Measure	Phase 1 - TAK-117 200 mg + Docetaxel 36 mg/m^2 n=14 Participants TAK-117 200 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, intravenous (IV) infusion, on Days 1 and 8 of the 21-day cycle up to 9 cycles (approximately 189 days).	Phase 1 - TAK-117 300 mg + Docetaxel 36 mg/m^2 TAK-117 300 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, IV infusion, on Days 1 and 8 of the 21-day cycle up to 6 cycles (approximately 126 days).
Recommended Phase 2 Dose of TAK-117 in Phase 1b	200 mg	—

PRIMARY outcome

Timeframe: Approximately 12 months in Phase 2

Population: Data was not analyzed as Phase 2 of the study was cancelled.

PFS is defined as the time from the date randomization to the date of first documented progressive disease (PD) or death as assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. PD is defined as 20% increase in the sum of the longest diameter of target lesions for measurable neoplastic disease.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: First dose of study drug through 30 days after the last dose of study drug (Up to Day 223)

Population: Safety population was defined as all participants who received at least 1 dose of any study drug.

Clinically significant change from baseline in vital sign measures will be assessed. Vital sign measurements included measurements of diastolic and systolic blood pressure, heart rate, and temperature.

Outcome measures

Outcome measures
Measure	Phase 1 - TAK-117 200 mg + Docetaxel 36 mg/m^2 n=6 Participants TAK-117 200 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, intravenous (IV) infusion, on Days 1 and 8 of the 21-day cycle up to 9 cycles (approximately 189 days).	Phase 1 - TAK-117 300 mg + Docetaxel 36 mg/m^2 n=8 Participants TAK-117 300 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, IV infusion, on Days 1 and 8 of the 21-day cycle up to 6 cycles (approximately 126 days).
Number of Participants With Significant Change in Vital Signs Reported as Adverse Events in Phase 1b Bradycardia	1 participants	0 participants
Number of Participants With Significant Change in Vital Signs Reported as Adverse Events in Phase 1b Sinus tachycardia	0 participants	1 participants

SECONDARY outcome

Timeframe: First dose of study drug through 30 days after the last dose of study drug (Up to Day 223)

Population: Safety population was defined as all participants who received at least 1 dose of any study drug.

Physical examination consists of examinations of the following body systems: (1) eyes; (2) ears, nose, throat; (3) cardiovascular system; (4) respiratory system; (5) gastrointestinal system; (6) dermatologic system; (7) extremities; (8) musculoskeletal system; (9) nervous system; (10) lymph nodes; and (11) physical examinations other than body systems described in (1) to (10).

Outcome measures

Outcome measures
Measure	Phase 1 - TAK-117 200 mg + Docetaxel 36 mg/m^2 n=6 Participants TAK-117 200 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, intravenous (IV) infusion, on Days 1 and 8 of the 21-day cycle up to 9 cycles (approximately 189 days).	Phase 1 - TAK-117 300 mg + Docetaxel 36 mg/m^2 n=8 Participants TAK-117 300 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, IV infusion, on Days 1 and 8 of the 21-day cycle up to 6 cycles (approximately 126 days).
Number of Participants With Significant Change in Physical Examination Reported as Adverse Events in Phase 1b	0 participants	1 participants

SECONDARY outcome

Timeframe: First dose of study drug through 30 days after the last dose of study drug (Up to Day 223)

Population: Safety population was defined as all participants who received at least 1 dose of any study drug.

A standard 12-lead ECG was performed.

Outcome measures

Outcome measures
Measure	Phase 1 - TAK-117 200 mg + Docetaxel 36 mg/m^2 n=6 Participants TAK-117 200 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, intravenous (IV) infusion, on Days 1 and 8 of the 21-day cycle up to 9 cycles (approximately 189 days).	Phase 1 - TAK-117 300 mg + Docetaxel 36 mg/m^2 n=8 Participants TAK-117 300 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, IV infusion, on Days 1 and 8 of the 21-day cycle up to 6 cycles (approximately 126 days).
Number of Participants With Electrocardiogram (ECG) Findings Reported as Adverse Events in Phase 1b Bradycardia	1 participants	0 participants
Number of Participants With Electrocardiogram (ECG) Findings Reported as Adverse Events in Phase 1b Tachycardia	0 participants	1 participants

SECONDARY outcome

Timeframe: First dose of study drug through 30 days after the last dose of study drug (Up to Day 223)

Population: Safety population was defined as all participants who received at least 1 dose of any study drug.

The number of participants with any markedly abnormal standard safety laboratory values (Chemistry, Hematology and Urinalysis) collected throughout study.

Outcome measures

Outcome measures
Measure	Phase 1 - TAK-117 200 mg + Docetaxel 36 mg/m^2 n=6 Participants TAK-117 200 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, intravenous (IV) infusion, on Days 1 and 8 of the 21-day cycle up to 9 cycles (approximately 189 days).	Phase 1 - TAK-117 300 mg + Docetaxel 36 mg/m^2 n=8 Participants TAK-117 300 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, IV infusion, on Days 1 and 8 of the 21-day cycle up to 6 cycles (approximately 126 days).
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b Hypocalcaemia	0 participants	1 participants
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b White blood cell count decreased	0 participants	1 participants
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b Hyperkalaemia	1 participants	0 participants
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b Hypernatraemia	0 participants	1 participants
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b Hypoalbuminaemia	1 participants	0 participants
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b Anemia	2 participants	2 participants
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b Hypokalemia	1 participants	3 participants
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b Hypomagnesemia	0 participants	3 participants
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b Hypophosphatemia	0 participants	3 participants
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b Aspartate aminotransferase increased	1 participants	2 participants
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b Febrile neutropenia	1 participants	2 participants
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b Hyponatremia	1 participants	2 participants
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b Hyperglycemia	0 participants	2 participants
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b Leukopenia	0 participants	1 participants
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b Pancytopenia	0 participants	1 participants
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b Thrombocytopenia	1 participants	0 participants
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b Blood creatinine increased	1 participants	1 participants
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b Alanine aminotransferase increased	0 participants	1 participants
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b Blood cholesterol increased	0 participants	1 participants
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b Neutrophil count decreased	1 participants	0 participants

SECONDARY outcome

Timeframe: From first dose of study drug to 30 days after last dose of study drug (Up to Day 223)

Population: Safety population was defined as all participants who received at least 1 dose of any study drug.

An Adverse Event (AE) is 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 treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event (SAE) is any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the above mentioned criteria. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

Outcome measures

Outcome measures
Measure	Phase 1 - TAK-117 200 mg + Docetaxel 36 mg/m^2 n=6 Participants TAK-117 200 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, intravenous (IV) infusion, on Days 1 and 8 of the 21-day cycle up to 9 cycles (approximately 189 days).	Phase 1 - TAK-117 300 mg + Docetaxel 36 mg/m^2 n=8 Participants TAK-117 300 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, IV infusion, on Days 1 and 8 of the 21-day cycle up to 6 cycles (approximately 126 days).
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Phase 1b TEAEs	6 participants	8 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Phase 1b SAEs	5 participants	6 participants

SECONDARY outcome

Timeframe: Approximately 12 months in Phase 2

Population: Data was not analyzed as Phase 2 of study was cancelled.

Vital signs (blood pressure, pulse rate, and oral temperature) measurements were collected throughout the study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately 12 months in Phase 2

Population: Data was not analyzed as Phase 2 of study was cancelled.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately 12 months in Phase 2

Population: Data was not analyzed as Phase 2 of study was cancelled.

Clinically significant changes from baseline in ECGs will be tabulated by time point including any unscheduled measurements.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately 12 months in Phase 2

Population: Safety population was defined as all participants who received at least 1 dose of any study drug.

The number of participants with any markedly abnormal standard safety laboratory values (Chemistry, Hematology and Urinalysis) collected throughout study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately 12 months in Phase 2

Population: Safety population was defined as all participants who received at least 1 dose of any study drug.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately 12 months in Phase 2

Population: Data was not analyzed as Phase 2 of the study was cancelled.

Response rate is defined as the percentage of participants with Complete Response (CR) + Partial Response (PR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1. According to RECIST: CR is defined as disappearance of all target lesions and PR is defined as 30% decrease in the sum of the longest diameter of target lesions.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately 12 months in Phase 2

Population: Data was not analyzed as Phase 2 of the study was cancelled.

Disease control rate is defined as percentage of participants with CR + PR + stable disease (SD). According to RECIST: CR is defined as disappearance of all target lesions, PR is defined as 30% decrease in the sum of the longest diameter of target lesions and SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter (LD) since the treatment started.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately 12 months in Phase 2

Population: Data was not analyzed as Phase 2 of the study was cancelled.

The duration of response is defined as the time from the date of first documentation of a response to the date of first documentation of progression of disease. As per RECIST 1.1, PD is defined as 20% increase in the sum of the longest diameter of target lesions for measurable neoplastic disease.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately 12 months in Phase 2

Population: Data was not analyzed as Phase 2 of the study was cancelled.

Time to progression is defined as the time from the date of randomization to the date of first documentation of progression of disease. As per RECIST 1.1, PD is defined as 20% increase in the sum of the longest diameter of target lesions for measurable neoplastic disease.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately 12 months in Phase 2

Population: Data was not analyzed as Phase 2 of the study was cancelled.

Overall survival is defined as the time from the date of randomization to the date of death.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 1 Day 1 pre-dose and 0.5, 1, 2, 4, 6, 8 and 24 hours post-dose

Population: The PK-evaluable population was defined as all participants for whom there are sufficient dosing and TAK-117 concentration-time data to permit non-compartmental PK analysis. Here 'Number Analyzed' are participants analyzed at the specific timepoint.

Outcome measures

Outcome measures
Measure	Phase 1 - TAK-117 200 mg + Docetaxel 36 mg/m^2 n=6 Participants TAK-117 200 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, intravenous (IV) infusion, on Days 1 and 8 of the 21-day cycle up to 9 cycles (approximately 189 days).	Phase 1 - TAK-117 300 mg + Docetaxel 36 mg/m^2 n=7 Participants TAK-117 300 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, IV infusion, on Days 1 and 8 of the 21-day cycle up to 6 cycles (approximately 126 days).
TAK-117 Plasma Concentration in Phase 1b Predose	114.00 ng/mL Standard Deviation 254.912	0.00 ng/mL Standard Deviation 0.000
TAK-117 Plasma Concentration in Phase 1b 0.5 Hour Postdose	1208.60 ng/mL Standard Deviation 1080.782	847.39 ng/mL Standard Deviation 966.346
TAK-117 Plasma Concentration in Phase 1b 1 Hour Postdose	1907.00 ng/mL Standard Deviation 1307.124	1973.29 ng/mL Standard Deviation 1688.210
TAK-117 Plasma Concentration in Phase 1b 2 Hours Postdose	2597.83 ng/mL Standard Deviation 1612.233	3021.43 ng/mL Standard Deviation 2162.417
TAK-117 Plasma Concentration in Phase 1b 4 Hours Postdose	2477.50 ng/mL Standard Deviation 1407.465	4185.71 ng/mL Standard Deviation 2156.439
TAK-117 Plasma Concentration in Phase 1b 6 Hours Postdose	2143.00 ng/mL Standard Deviation 1290.395	3648.57 ng/mL Standard Deviation 1636.892
TAK-117 Plasma Concentration in Phase 1b 8 Hours Postdose	1902.50 ng/mL Standard Deviation 1210.553	3677.14 ng/mL Standard Deviation 1941.020
TAK-117 Plasma Concentration in Phase 1b 24 Hours Postdose	652.17 ng/mL Standard Deviation 472.315	1771.57 ng/mL Standard Deviation 1347.864

SECONDARY outcome

Timeframe: Cycle 1 Day 1 pre-dose and 0.5, 1, 2, 4, 6, 8 and 24 hours post-dose

Population: This analysis was not performed due to lack of data.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 1 Day 1 pre-dose and up to 24 hours post-dose

Population: This analysis was not performed due to lack of data.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 1 Day 1 pre-dose and up to 24 hours post-dose

Population: This analysis was not performed due to lack of data.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 1 Day 1 pre-dose and up to 24 hours post-dose

Population: This analysis was not performed due to lack of data.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 1 Day 1 pre-dose and up to 24 hours post-dose

Population: This analysis was not performed due to lack of data.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 1 Day 1 pre-dose and up to 24 hours post-dose

Population: This analysis was not performed due to lack of data.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 day post docetaxel dose

Population: Data was not analyzed as Phase 2 of study was cancelled.

Outcome measures

Outcome data not reported

Adverse Events

Phase 1 - TAK-117 200 mg + Docetaxel 36 mg/m^2

Serious events: 5 serious events

Other events: 6 other events

Deaths: 1 deaths

Phase 1 - TAK-117 300 mg + Docetaxel 36 mg/m^2

Serious events: 6 serious events

Other events: 8 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
Publication restrictions are in place

Restriction type: OTHER

Measure	Phase 1 - TAK-117 200 mg + Docetaxel 36 mg/m^2 n=6 participants at risk TAK-117 200 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, intravenous (IV) infusion, on Days 1 and 8 of the 21-day cycle up to 9 cycles (approximately 189 days).	Phase 1 - TAK-117 300 mg + Docetaxel 36 mg/m^2 n=8 participants at risk TAK-117 300 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, IV infusion, on Days 1 and 8 of the 21-day cycle up to 6 cycles (approximately 126 days).
Infections and infestations Pneumonia	33.3% 2/6 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.5% 1/8 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Bacterial sepsis	0.00% 0/6 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.5% 1/8 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Legionella infection	0.00% 0/6 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.5% 1/8 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Sepsis	0.00% 0/6 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.5% 1/8 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Diarrhoea	33.3% 2/6 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.5% 1/8 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Nausea	0.00% 0/6 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	25.0% 2/8 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Vomiting	0.00% 0/6 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	25.0% 2/8 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Gastric haemorrhage	16.7% 1/6 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Odynophagia	0.00% 0/6 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.5% 1/8 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Oesophagitis	0.00% 0/6 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.5% 1/8 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Stomatitis	16.7% 1/6 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Respiratory failure	33.3% 2/6 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/6 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.5% 1/8 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/6 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.5% 1/8 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Febrile neutropenia	16.7% 1/6 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	25.0% 2/8 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Cardio-respiratory arrest	16.7% 1/6 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Cardiogenic shock	16.7% 1/6 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Dehydration	0.00% 0/6 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	25.0% 2/8 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/6 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.5% 1/8 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Reproductive system and breast disorders Postmenopausal haemorrhage	0.00% 0/6 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.5% 1/8 • First dose of study drug through 30 days from the last dose (up to Day 223) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.