Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Paclitaxel

Docetaxel

Albumin-Bound Paclitaxel

Carboplatin

Pevonedistat

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Enzyme Inhibitors

MLN4924 (intravenously \[IV\]) in participants in a 21-day cycle:

* MLN4924 on Days 1,3,5 of each cycle

MLN4924

Paclitaxel (IV) in a 21-day cycle:

* Paclitaxel on Day 1 of each cycle

Gemcitabine (IV) in participants in a 28-day cycle:

-Gemcitabine on Days 1,8,15 of each cycle

Docetaxel (IV) in participants in a 21-day cycle:

- Docetaxel on Day 1 of each cycle

Carboplatin (IV) in participants in a 21-day cycle:

- Carboplatin on Day 1 of each cycle

Medical Monitor

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.

Dose Escalation, Multi-arm Study of MLN4924 Plus Docetaxel, Gemcitabine, or Combination of Carboplatin and Paclitaxel in Participants With Solid Tumors

A Phase 1b, Open-Label, Dose Escalation, Multi-arm Study of MLN4924 Plus Docetaxel, Gemcitabine, or Combination of Carboplatin and Paclitaxel in Patients With Solid Tumors

Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

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.

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.

The number of participants analyzed includes only those participants who had data available for this measure.

Millennium Pharmaceuticals, Inc.

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.

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).

Arm 1: MLN4924 15 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).

Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2

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).

Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6

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).

Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/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).

Arm 2:MLN4924 20 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).

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, 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).

Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Body surface area (BSA)

The safety population was defined as all participants who received at least 1 dose of any study drug.

Medical Director

TEAE

Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Anaemia

Aspartate aminotransferase increased

Alanine aminotransferase increased

Neutrophil count decreased

Neutropenia

Thrombocytopenia

Platelet count decreased

White blood cell count decreased

Hypomagnesaemia

Blood creatinine increased

Blood alkaline phosphatase increased

Lymphocyte count decreased

Blood bilirubin increased

Hypophosphataemia

Hypokalaemia

Gamma-glutamyltransferase increased

Blood glucose increased

Liver function test abnormal

Haematocrit decreased

Red blood cell count decreased

Hypoglycaemia

Hyponatraemia

Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings

Tachycardia

Hypotension

Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings

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.

Percentage of Participants With Objective Response

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.

Duration of Response

Cycle 1 Day 1: End-dose

Cycle 1 Day 1: 1.5 hours post dose

Cycle 1 Day 1: 3 hours post dose

Cycle 1 Day 1: 20 hours post dose

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.

Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924

Cycle 1 Day 1: 6 hours post dose

Cycle 1 Day 1: 7 hours post dose

Cycle 1 Day 5: End-dose

Cycle 1 Day 5: 1.5 hours post dose

Cycle 1 Day 5: 3 hours post dose

Cycle 1 Day 5: 6 hours post dose

Cycle 1 Day 5: 7 hours post dose

Cycle 1 Day 5: 20 hours post dose

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.

MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924

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 progressive disease (PD) (up to Cycle 52).

Spots Global Cancer Trial Database for Dose Escalation, Multi-arm Study of MLN4924 Plus Docetaxel, Gemcitabine, or Combination of Carboplatin and Paclitaxel in Participants With Solid Tumors

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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