Solid Tumors
Conditions
Keywords
MLN4924, Solid Tumors
Brief summary
The purpose of this study is to establish the maximum tolerated dose (MTD) and assess the safety and tolerability of MLN4924 (pevonedistat) in combination with docetaxel, paclitaxel and carboplatin, and gemcitabine in participants with solid tumors.
Interventions
DRUGMLN4924
MLN4924 (intravenously \[IV\]) in participants in a 21-day cycle: * MLN4924 on Days 1,3,5 of each cycle
DRUGPaclitaxel
Paclitaxel (IV) in a 21-day cycle: * Paclitaxel on Day 1 of each cycle
DRUGGemcitabine
Gemcitabine (IV) in participants in a 28-day cycle: -Gemcitabine on Days 1,8,15 of each cycle
DRUGDocetaxel
Docetaxel (IV) in participants in a 21-day cycle: \- Docetaxel on Day 1 of each cycle
DRUGCarboplatin
Carboplatin (IV) in participants in a 21-day cycle: \- Carboplatin on Day 1 of each cycle
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 18 years of age or older 2. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 3. Have a histologically or cytologically confirmed metastatic or locally advanced and incurable solid tumor that is felt to be appropriate for treatment with 1 of the 3 chemotherapy regimens in this study, or have progressed despite standard therapy, or for whom conventional therapy is not considered effective. The tumor must be radiographically or clinically evaluable and/or measurable 4. Recovered (that is, \<=Grade 1 toxicity) from the effects of prior antineoplastic therapy 5. Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to practice true abstinence 6. Male participants who agree to practice effective barrier contraception or agree to practice true abstinence 7. Voluntary written consent must be given before performance of any study-related procedure 8. Suitable venous access for the study-required blood sampling 9. Adequate clinical laboratory values during the screening period as specified in the protocol 10. Participants who are willing to refrain from donating blood for at least 90 days after their final dose of MLN4924 and (for male participants) willing to refrain from donating semen for at least 4 months after their final dose of MLN4924 11. Availability of fixed tumor specimen (block or slides) for exploratory biomarker analysis. If no slides or block are available, fresh tumor biopsies should be obtained and used for these assessments
Exclusion criteria
1. Major surgery within 14 days before the first dose of study drug 2. Female participants who are lactating or pregnant 3. Active uncontrolled infection or severe infectious disease 4. Receiving antibiotic therapy within 14 days before the first dose of study treatment 5. Life-threatening illness unrelated to cancer 6. Known hypersensitivity to study-assigned chemotherapy 7. Prior treatment with MLN4924; however, prior treatment with docetaxel, paclitaxel,carboplatin, and gemcitabine is allowed 8. History of severe hypersensitivity reactions to docetaxel (polysorbate 80-based formulations) for participants to be enrolled in Arm 1 (MLN4924 + docetaxel), history of hypersensitivity to carboplatin for participants to be enrolled in Arm 2 (MLN4924 + paclitaxel + carboplatin), or history of severe hypersensitivity to paclitaxel (cremophor-based formulations) for participants to be enrolled in Arm 2 9. Persistent diarrhea (greater than Grade 2) lasting \>3 days within 2 weeks before the first dose of study treatment 10. Systemic antineoplastic therapy within 21 days before the first dose of study drug 11. Radiotherapy within 14 days preceding the first dose of study treatment 12. Prior treatment with radiation therapy involving greater than or equal to (\>=) 25% of the hematopoietically active bone marrow 13. Treatment with cytochrome P450 3A (CYP3A) inducers within 14 days before the first dose of MLN4924. Treatment with CYP3A inhibitors within 14 days before the first dose of MLN4924; however, voriconazole and fluconazole need only be stopped for 3 days before MLN4924. Participants must have no history of amiodarone use in the 6 months before the first dose of MLN4924 14. Clinically uncontrolled central nervous system (CNS) involvement 15. Any serious medical or psychiatric illness 16. Treatment with any investigational products 21 days prior to treatment 17. Unwilling or unable to refrain from using statins 24 hours before, the day of, and 24 hours after each MLN4924 administration 18. Known human immunodeficiency virus (HIV) positive or hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection 19. Known hepatic cirrhosis 20. Known cardiac/cardiopulmonary disease 21. Left ventricular ejection fraction 23. with a cardiac pacer whose heart rate is set at a fixed rate and participants on concomitant medication that may limit increase in heart rate in response to hypotension 24 History of severe intolerance to cytotoxic agent(s) given in the assigned arm
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Baseline up to 30 days after the last dose of study drug (up to 5 years) |
| Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Baseline up to 30 days after the last dose of study drug (up to 5 years) |
| Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings | Baseline up to 30 days after the last dose of study drug (up to 5 years) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response | Screening, Cycle 2 Days 15 (Arm 1, 2a, and 2) and 22 (Arm 3) then every other Cycle thereafter up to 30 days after the last dose of study drug (up to 5 years) (Cycle Length = 21 days [Arm 1, 2a, and 2] and 28 days [Arm 3]) | Percentage of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: complete disappearance of all target lesions and non-target disease, with exception of nodal disease; all nodes, both target and non-target, must decrease to normal (short axis less than \[\<\] 10 millimeter \[mm\]); no new lesions. PR: greater than or equal to (\>=) 30 percent (%) decrease under baseline of sum of diameters of all target lesions; short axis was used in sum for target nodes, while longest diameter was used in sum for all other target lesions; no unequivocal progression of non-target disease; no new lesions. |
| MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Days 1 and 5 pre-dose and at multiple time points (up to 20 hours) post-dose (Cycle Length=21 days [Arm 1 and 2]) | The number of participants analyzed includes only those participants who had data available for this measure. |
| Duration of Response | From the date of first documented response (CR or PR) to the date of first documented PD or the date of last disease assessment if the participants discontinued the study before PD (up to 5 years) | Duration of response: time from the date of first documented response per the investigator response assessment (CR or PR) to the date of PD or the date of last disease assessment if the participant discontinued the study before PD using RECIST 1.1 CR: complete disappearance of all target lesions and non-target disease, with exception of nodal disease; all nodes, both target and non-target, must decrease to normal (short axis \<10 mm); no new lesions. PR: \>=30% decrease under baseline of sum of diameters of all target lesions; short axis was used in sum for target nodes, while longest diameter was used in sum for all other target lesions; no unequivocal progression of non-target disease; no new lesions. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in sum of diameters of target lesions, taking as reference smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. |
| Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1 pre-dose and at multiple time points (up to 20 hours) post-dose (Cycle Length=21 days [Arm 1 and 2] and 28 days [Arm 3]) | — |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 6 investigative sites in the United States from 10 June 2013 to 21 May 2018.
Pre-assignment details
Participants with solid tumors were enrolled to receive MLN4924 in combination with docetaxel (Arm 1), paclitaxel + carboplatin (Arm 2), or gemcitabine (Arm 3) during the Dose-escalation and maximum tolerated dose (MTD) expansion portion of this study. Participants in Lead-in cohort received MLN4924 + carboplatin only (Arm 2a).
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 MLN4924 15 milligram per square meter (mg/m\^2), infusion, intravenously, once on Days 1, 3, and 5 and docetaxel 75 mg/m\^2, infusion, intravenously, once on Day 1 before administration of MLN4924 in a 21-day cycle up to symptomatic deterioration or PD (up to Cycle 52). | 4 |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 MLN4924 25 mg/m\^2, infusion, intravenously, once on Days 1, 3, and 5 and docetaxel 75 mg/m\^2, infusion, intravenously, once on Day 1 before administration of MLN4924 in a 21-day cycle up to symptomatic deterioration or PD (up to Cycle 52). | 18 |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 MLN4924 15 mg/m\^2, infusion, intravenously, once on Days 1, 3, and 5 and carboplatin AUC6, infusion intravenously once on Day 1 before administration of MLN4924 in a 21-day cycle up to symptomatic deterioration or PD (up to Cycle 52). | 6 |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 MLN4924 15 mg/m\^2, infusion, intravenously, once on Days 1, 3, and 5 and paclitaxel 175 mg/m\^2, infusion, intravenously, once on Day 1 followed by carboplatin AUC5, infusion, intravenously once on Day 1 before administration of MLN4924 in a 21-day cycle up to symptomatic deterioration or PD (up to Cycle 52). | 7 |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 MLN4924 20 mg/m\^2, infusion, intravenously, once on Days 1, 3, and 5 and paclitaxel 175 mg/m\^2, infusion, intravenously, once on Day 1 followed by carboplatin AUC5, infusion, intravenously once on Day 1 before administration of MLN4924 in a 21-day cycle up to symptomatic deterioration or PD (up to Cycle 52). | 12 |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 MLN4924 25 mg/m\^2, infusion, intravenously, once on Days 1, 3, and 5 and paclitaxel 175 mg/m\^2, infusion, intravenously, once on Day 1 followed by carboplatin AUC5 infusion, intravenously once on Day 1 before administration of MLN4924 in a 21-day cycle up to symptomatic deterioration or PD (up to Cycle 52). | 7 |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 MLN4924 25 mg/m\^2, infusion, intravenously, once on Days 1, 8, and 15 and gemcitabine 1000 mg/m\^2, infusion, intravenously, once on Days 1, 8, and 15 before administration of MLN4924 in a 28-day cycle up to symptomatic deterioration or PD (up to Cycle 52). | 10 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 4 | 0 | 1 | 0 | 2 | 4 |
| Overall Study | Other | 0 | 2 | 1 | 0 | 4 | 0 | 1 |
| Overall Study | Progressive Disease | 3 | 11 | 5 | 6 | 7 | 4 | 3 |
| Overall Study | Symptomatic Deterioration | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 0 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 57.8 years STANDARD_DEVIATION 2.99 | 60.0 years STANDARD_DEVIATION 9.82 | 56.8 years STANDARD_DEVIATION 9.56 | 58.1 years STANDARD_DEVIATION 10.65 | 57.9 years STANDARD_DEVIATION 14.34 | 59.0 years STANDARD_DEVIATION 12 | 59.7 years STANDARD_DEVIATION 14.45 | 58.8 years STANDARD_DEVIATION 11.19 |
| Body surface area (BSA) | 1.9 square meter (m^2) STANDARD_DEVIATION 0.32 | 1.9 square meter (m^2) STANDARD_DEVIATION 0.28 | 1.8 square meter (m^2) STANDARD_DEVIATION 0.29 | 2.0 square meter (m^2) STANDARD_DEVIATION 0.28 | 1.9 square meter (m^2) STANDARD_DEVIATION 0.32 | 1.9 square meter (m^2) STANDARD_DEVIATION 0.17 | 1.9 square meter (m^2) STANDARD_DEVIATION 0.25 | 1.9 square meter (m^2) STANDARD_DEVIATION 0.27 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 14 Participants | 6 Participants | 7 Participants | 11 Participants | 7 Participants | 7 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 5 Participants | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 13 Participants | 4 Participants | 5 Participants | 11 Participants | 7 Participants | 9 Participants | 52 Participants |
| Region of Enrollment United States | 4 Participants | 18 Participants | 6 Participants | 7 Participants | 12 Participants | 7 Participants | 10 Participants | 64 Participants |
| Sex: Female, Male Female | 2 Participants | 11 Participants | 4 Participants | 4 Participants | 8 Participants | 1 Participants | 4 Participants | 34 Participants |
| Sex: Female, Male Male | 2 Participants | 7 Participants | 2 Participants | 3 Participants | 4 Participants | 6 Participants | 6 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 2 / 18 | 0 / 6 | 0 / 7 | 0 / 12 | 1 / 7 | 3 / 10 |
| other Total, other adverse events | 4 / 4 | 18 / 18 | 6 / 6 | 6 / 7 | 12 / 12 | 7 / 7 | 10 / 10 |
| serious Total, serious adverse events | 1 / 4 | 9 / 18 | 3 / 6 | 2 / 7 | 3 / 12 | 1 / 7 | 7 / 10 |
Outcome results
Primary
Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Baseline up to 30 days after the last dose of study drug (up to 5 years)
Population: The safety population was defined as all participants who received at least 1 dose of any study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAE | 4 Participants |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAE | 1 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAE | 9 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAE | 18 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAE | 6 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAE | 3 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAE | 2 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAE | 7 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAE | 12 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAE | 3 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAE | 7 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAE | 1 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAE | 10 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAE | 7 Participants |
Primary
Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings
Time frame: Baseline up to 30 days after the last dose of study drug (up to 5 years)
Population: The safety population was defined as all participants who received at least 1 dose of any study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood bilirubin increased | 0 Participants |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Aspartate aminotransferase increased | 0 Participants |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Platelet count decreased | 0 Participants |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Anaemia | 1 Participants |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Gamma-glutamyltransferase increased | 0 Participants |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Haematocrit decreased | 0 Participants |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Neutropenia | 1 Participants |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypophosphataemia | 0 Participants |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hyponatraemia | 0 Participants |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Lymphocyte count decreased | 0 Participants |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Thrombocytopenia | 0 Participants |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood alkaline phosphatase increased | 0 Participants |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Liver function test abnormal | 0 Participants |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypoglycaemia | 0 Participants |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Alanine aminotransferase increased | 0 Participants |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood creatinine increased | 1 Participants |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | White blood cell count decreased | 1 Participants |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypokalaemia | 1 Participants |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood glucose increased | 0 Participants |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypomagnesaemia | 0 Participants |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Red blood cell count decreased | 0 Participants |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Neutrophil count decreased | 1 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypomagnesaemia | 2 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood bilirubin increased | 1 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood alkaline phosphatase increased | 2 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Lymphocyte count decreased | 1 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypoglycaemia | 1 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Alanine aminotransferase increased | 7 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Anaemia | 4 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Red blood cell count decreased | 1 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Neutrophil count decreased | 5 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Haematocrit decreased | 1 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Neutropenia | 1 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hyponatraemia | 0 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Liver function test abnormal | 1 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Thrombocytopenia | 1 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood glucose increased | 1 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Platelet count decreased | 1 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Gamma-glutamyltransferase increased | 1 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | White blood cell count decreased | 2 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Aspartate aminotransferase increased | 6 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypokalaemia | 0 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypophosphataemia | 2 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood creatinine increased | 2 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Platelet count decreased | 2 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Neutrophil count decreased | 1 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Red blood cell count decreased | 0 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Gamma-glutamyltransferase increased | 0 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood alkaline phosphatase increased | 0 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Alanine aminotransferase increased | 1 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypophosphataemia | 0 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | White blood cell count decreased | 0 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood creatinine increased | 0 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Lymphocyte count decreased | 0 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypokalaemia | 1 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood bilirubin increased | 0 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypoglycaemia | 0 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Liver function test abnormal | 0 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Anaemia | 2 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Thrombocytopenia | 3 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Neutropenia | 1 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Haematocrit decreased | 0 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood glucose increased | 0 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypomagnesaemia | 2 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hyponatraemia | 0 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Aspartate aminotransferase increased | 2 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood glucose increased | 0 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Anaemia | 2 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Aspartate aminotransferase increased | 2 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Alanine aminotransferase increased | 1 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Neutrophil count decreased | 3 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Neutropenia | 1 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Thrombocytopenia | 1 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Platelet count decreased | 3 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | White blood cell count decreased | 0 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypomagnesaemia | 0 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood creatinine increased | 0 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood alkaline phosphatase increased | 0 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Lymphocyte count decreased | 0 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood bilirubin increased | 0 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypophosphataemia | 0 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypokalaemia | 0 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Gamma-glutamyltransferase increased | 0 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Liver function test abnormal | 0 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Haematocrit decreased | 0 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Red blood cell count decreased | 0 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypoglycaemia | 0 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hyponatraemia | 0 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypophosphataemia | 1 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Neutrophil count decreased | 3 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Platelet count decreased | 2 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Liver function test abnormal | 0 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood bilirubin increased | 1 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Thrombocytopenia | 3 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood glucose increased | 0 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Aspartate aminotransferase increased | 5 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Anaemia | 7 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Neutropenia | 4 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypomagnesaemia | 0 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Red blood cell count decreased | 0 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood creatinine increased | 0 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hyponatraemia | 1 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypokalaemia | 1 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Lymphocyte count decreased | 1 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Alanine aminotransferase increased | 4 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | White blood cell count decreased | 4 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Haematocrit decreased | 0 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood alkaline phosphatase increased | 0 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypoglycaemia | 1 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Gamma-glutamyltransferase increased | 1 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypophosphataemia | 0 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood bilirubin increased | 0 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypomagnesaemia | 1 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | White blood cell count decreased | 0 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypokalaemia | 0 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Platelet count decreased | 2 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Anaemia | 2 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Gamma-glutamyltransferase increased | 0 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Thrombocytopenia | 3 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood glucose increased | 0 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Neutropenia | 4 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Liver function test abnormal | 0 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Neutrophil count decreased | 1 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Haematocrit decreased | 0 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Alanine aminotransferase increased | 1 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Red blood cell count decreased | 0 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Aspartate aminotransferase increased | 2 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hyponatraemia | 0 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood alkaline phosphatase increased | 0 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Lymphocyte count decreased | 1 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood creatinine increased | 0 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypoglycaemia | 0 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Haematocrit decreased | 0 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Alanine aminotransferase increased | 3 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypoglycaemia | 0 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypokalaemia | 0 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Anaemia | 3 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | White blood cell count decreased | 0 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypomagnesaemia | 0 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Red blood cell count decreased | 0 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Aspartate aminotransferase increased | 2 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood creatinine increased | 1 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hypophosphataemia | 0 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Neutropenia | 3 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood glucose increased | 0 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Thrombocytopenia | 3 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Lymphocyte count decreased | 0 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Liver function test abnormal | 0 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Neutrophil count decreased | 1 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood alkaline phosphatase increased | 1 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Gamma-glutamyltransferase increased | 0 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Hyponatraemia | 0 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Platelet count decreased | 3 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings | Blood bilirubin increased | 1 Participants |
Primary
Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings
Time frame: Baseline up to 30 days after the last dose of study drug (up to 5 years)
Population: The safety population was defined as all participants who received at least 1 dose of any study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings | Hypotension | 1 Participants |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings | Tachycardia | 0 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings | Tachycardia | 2 Participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings | Hypotension | 3 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings | Tachycardia | 1 Participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings | Hypotension | 2 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings | Tachycardia | 0 Participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings | Hypotension | 2 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings | Hypotension | 0 Participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings | Tachycardia | 0 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings | Tachycardia | 0 Participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings | Hypotension | 2 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings | Tachycardia | 0 Participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings | Hypotension | 1 Participants |
Secondary
Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924
Time frame: Cycle 1 Day 1 pre-dose and at multiple time points (up to 20 hours) post-dose (Cycle Length=21 days [Arm 1 and 2] and 28 days [Arm 3])
Population: The safety population was defined as all participants who received at least 1 dose of any study drug. The number of participants analyzed includes only those participants who had data available for this measure. This outcome measure was planned to be assessed only in the Dose-escalation phases of Arms 1, 2, and 3.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: End-dose | 163.8 nanogram per milliliter (ng/ml) | Standard Deviation 109.15 |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 1.5 hours post dose | 82.0 nanogram per milliliter (ng/ml) | Standard Deviation 39.97 |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 3 hours post dose | 48.0 nanogram per milliliter (ng/ml) | Standard Deviation 12.05 |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 20 hours post dose | 7.5 nanogram per milliliter (ng/ml) | Standard Deviation 1.5 |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 3 hours post dose | 95.8 nanogram per milliliter (ng/ml) | Standard Deviation 19.7 |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 1.5 hours post dose | 130.6 nanogram per milliliter (ng/ml) | Standard Deviation 46.94 |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: End-dose | 197.1 nanogram per milliliter (ng/ml) | Standard Deviation 51.94 |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 20 hours post dose | 14.6 nanogram per milliliter (ng/ml) | Standard Deviation 4.81 |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 20 hours post dose | 23.4 nanogram per milliliter (ng/ml) | Standard Deviation 9.19 |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 3 hours post dose | 152.4 nanogram per milliliter (ng/ml) | Standard Deviation 56.19 |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 1.5 hours post dose | 156.8 nanogram per milliliter (ng/ml) | Standard Deviation 53.46 |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: End-dose | 275.7 nanogram per milliliter (ng/ml) | Standard Deviation 98.67 |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: End-dose | 257.3 nanogram per milliliter (ng/ml) | Standard Deviation 110.05 |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 20 hours post dose | 34.6 nanogram per milliliter (ng/ml) | Standard Deviation 25.09 |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 1.5 hours post dose | 192.7 nanogram per milliliter (ng/ml) | Standard Deviation 80.35 |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 3 hours post dose | 138.0 nanogram per milliliter (ng/ml) | Standard Deviation 73.1 |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 3 hours post dose | 186.9 nanogram per milliliter (ng/ml) | Standard Deviation 32.3 |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 20 hours post dose | 24.4 nanogram per milliliter (ng/ml) | Standard Deviation 10.81 |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 1.5 hours post dose | 246.7 nanogram per milliliter (ng/ml) | Standard Deviation 47.24 |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: End-dose | 372.7 nanogram per milliliter (ng/ml) | Standard Deviation 120.93 |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 1.5 hours post dose | 160.5 nanogram per milliliter (ng/ml) | Standard Deviation 122.07 |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 3 hours post dose | 103.0 nanogram per milliliter (ng/ml) | Standard Deviation 39 |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 20 hours post dose | 14.2 nanogram per milliliter (ng/ml) | Standard Deviation 5.09 |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: End-dose | 222.0 nanogram per milliliter (ng/ml) | Standard Deviation 87.62 |
Secondary
Duration of Response
Duration of response: time from the date of first documented response per the investigator response assessment (CR or PR) to the date of PD or the date of last disease assessment if the participant discontinued the study before PD using RECIST 1.1 CR: complete disappearance of all target lesions and non-target disease, with exception of nodal disease; all nodes, both target and non-target, must decrease to normal (short axis \<10 mm); no new lesions. PR: \>=30% decrease under baseline of sum of diameters of all target lesions; short axis was used in sum for target nodes, while longest diameter was used in sum for all other target lesions; no unequivocal progression of non-target disease; no new lesions. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in sum of diameters of target lesions, taking as reference smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Time frame: From the date of first documented response (CR or PR) to the date of first documented PD or the date of last disease assessment if the participants discontinued the study before PD (up to 5 years)
Population: The response-evaluable population is defined as all participants who receive at least 1 dose of study drug, have measurable disease at baseline, and have at least 1 post baseline disease assessment. The number of participants analyzed includes only those participants who had data available for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Duration of Response | 2.880 months | Standard Deviation 2.7644 |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Duration of Response | 2.270 months | — |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Duration of Response | 16.153 months | Standard Deviation 15.9867 |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Duration of Response | 7.015 months | Standard Deviation 1.1384 |
Secondary
MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924
The number of participants analyzed includes only those participants who had data available for this measure.
Time frame: Cycle 1 Days 1 and 5 pre-dose and at multiple time points (up to 20 hours) post-dose (Cycle Length=21 days [Arm 1 and 2])
Population: The safety population was defined as all participants who received at least 1 dose of any study drug. This outcome measure was planned to be assessed for participants who received the MTD in Arms 1 and 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 7 hours post dose | 63.4 ng/ml | Standard Deviation 24.87 |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 20 hours post dose | 14.2 ng/ml | Standard Deviation 5.39 |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 5: End-dose | 211.1 ng/ml | Standard Deviation 116.43 |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: End-dose | 152.8 ng/ml | Standard Deviation 83.67 |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 5: 1.5 hours post dose | 115.3 ng/ml | Standard Deviation 42.54 |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 3 hours post dose | 86.4 ng/ml | Standard Deviation 29.16 |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 5: 3 hours post dose | 96.7 ng/ml | Standard Deviation 53.48 |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 5: 7 hours post dose | 38.3 ng/ml | Standard Deviation 17.84 |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 5: 20 hours post dose | 9.8 ng/ml | Standard Deviation 2.07 |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 1.5 hours post dose | 137.3 ng/ml | Standard Deviation 37.19 |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 5: 20 hours post dose | 10.9 ng/ml | Standard Deviation 3.4 |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 5: 6 hours post dose | 76.5 ng/ml | Standard Deviation 4.97 |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: End-dose | 429.8 ng/ml | Standard Deviation 95.87 |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 1.5 hours post dose | 253.6 ng/ml | Standard Deviation 19.65 |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 3 hours post dose | 192.8 ng/ml | Standard Deviation 39.14 |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 6 hours post dose | 136.3 ng/ml | Standard Deviation 14.73 |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 5: End-dose | 253.2 ng/ml | Standard Deviation 56.6 |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 5: 1.5 hours post dose | 171.0 ng/ml | Standard Deviation 19.44 |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 5: 3 hours post dose | 118.4 ng/ml | Standard Deviation 19.69 |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924 | Cycle 1 Day 1: 20 hours post dose | 30.2 ng/ml | Standard Deviation 7.98 |
Secondary
Percentage of Participants With Objective Response
Percentage of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: complete disappearance of all target lesions and non-target disease, with exception of nodal disease; all nodes, both target and non-target, must decrease to normal (short axis less than \[\<\] 10 millimeter \[mm\]); no new lesions. PR: greater than or equal to (\>=) 30 percent (%) decrease under baseline of sum of diameters of all target lesions; short axis was used in sum for target nodes, while longest diameter was used in sum for all other target lesions; no unequivocal progression of non-target disease; no new lesions.
Time frame: Screening, Cycle 2 Days 15 (Arm 1, 2a, and 2) and 22 (Arm 3) then every other Cycle thereafter up to 30 days after the last dose of study drug (up to 5 years) (Cycle Length = 21 days [Arm 1, 2a, and 2] and 28 days [Arm 3])
Population: The response-evaluable population was defined as all the participants who received at least 1 dose of MLN4924, had measurable disease at baseline, and had at least 1 post baseline disease assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Percentage of Participants With Objective Response | CR | 0 percentage of participants |
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | Percentage of Participants With Objective Response | PR | 0 percentage of participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Percentage of Participants With Objective Response | CR | 0 percentage of participants |
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | Percentage of Participants With Objective Response | PR | 19 percentage of participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Percentage of Participants With Objective Response | CR | 0 percentage of participants |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | Percentage of Participants With Objective Response | PR | 17 percentage of participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Percentage of Participants With Objective Response | CR | 0 percentage of participants |
| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | Percentage of Participants With Objective Response | PR | 0 percentage of participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Percentage of Participants With Objective Response | CR | 18 percentage of participants |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Percentage of Participants With Objective Response | PR | 36 percentage of participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Percentage of Participants With Objective Response | CR | 0 percentage of participants |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | Percentage of Participants With Objective Response | PR | 40 percentage of participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Percentage of Participants With Objective Response | CR | 0 percentage of participants |
| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | Percentage of Participants With Objective Response | PR | 0 percentage of participants |