The primary purpose of this study is to determine the safety profile and the maximum tolerated doses (MTDs)/ potential recommended phase 2 doses (RP2Ds) of the combination treatments of MLN2480 + MLN0128, MLN2480 + alisertib, MLN2480 + paclitaxel, MLN2480 + cetuximab, and MLN2480 + irinotecan in participants with advanced nonhematologic malignancies.
Name: MLN2480
Description: MLN2480.Type: DrugMLN2480 + MLN0128 MLN2480 + Alisertib MLN2480 + Paclitaxel MLN2480 + Cetuximab ML2480 + Irinotecan
Name: MLN0128
Description: MLN0128.Type: DrugMLN2480 + MLN0128
Name: Alisertib
Description: Alisertib.Type: DrugMLN2480 + Alisertib
Name: Paclitaxel
Description: Paclitaxel.Type: DrugMLN2480 + Paclitaxel
Name: Cetuximab
Description: Cetuximab.Type: DrugMLN2480 + Cetuximab
Name: Irinotecan
Description: Irinotecan.Type: DrugML2480 + Irinotecan
Description: An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. Serious adverse event (SAE) means any untoward medical occurrence that at any dose results in death, is life-threatening, requires inparticipant hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. Relationship of each AE to study drug will be determined by the Investigator.
Measure: Number of Participants With Adverse Events (AEs) Time: From Day 1, Cycle 1 through 30 days after the last dose of study drug (up to 13 months)Description: Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
Measure: Cmax: Maximum Observed Plasma Concentration for MLN2480, MLN0128, Alisertib, Cetuximab, and Irinotecan Time: Cycle 1, Day 10 pre-dose and up to 48 hours post-doseDescription: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.
Measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN2480, MLN0128, Alisertib, Cetuximab, and Irinotecan Time: Cycle 1, Day 10 pre-dose and up to 48 hours post-doseDescription: AUC(0-tau) is a measure of the area under the plasma concentration-time curve from time 0 to time tau over a dosing interval, where tau is the length of the dosing interval.
Measure: AUC(0-tau): Area under the Plasma Concentration-time Curve from Time 0 to Time tau Over the Dosing Interval for MLN2480, MLN0128, Alisertib, Cetuximab, and Irinotecan Time: Cycle 1, Day 10 pre-dose and up to 48 hours post-doseDescription: Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
Measure: Cmax: Maximum Observed Plasma Concentration for Paclitaxel Time: Cycle 1, Day 15 pre-dose and up to 48 hours post-doseDescription: AUC(0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.
Measure: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Paclitaxel Time: Cycle 1, Day 15 pre-dose and up to 48 hours post-doseDescription: Terminal Phase Elimination Half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.
Measure: Terminal Elimination Half-life (T1/2) Pharmacokinetic Parameter for Paclitaxel Time: Cycle 1, Day 15 pre-dose and up to 48 hours post-doseDescription: ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions.
Measure: Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) Time: From 27 days, every other cycle, starting with Cycle 2 until disease progression, death or study closure (up to 13 months)Description: Time to response is defined as the time from the participant's date of enrollment to the date of the first documentation of a confirmed response.
Measure: Time to Response Time: From date of enrollment to the date of the first documentation of a confirmed response (up to 13 months)Description: Duration of response is defined as the time from the date of first documentation of a confirmed response to the date of first documented progression of disease.
Measure: Duration of Response Time: From first documented response until disease progression (up to 13 months)Description: PFS is defined as the time from the date of first study drug administration to the date of first documentation of disease progression or death.
Measure: Progression Free Survival (PFS) Time: Day 27 of every other 28-day cycle starting with Cycle 2 and 30 days after the last dose of study medication (up to 13 months)Description: AUC(0-tlast) is a measure of total plasma exposure to the drug from time 0 to time of the last quantifiable concentration.
Measure: AUC(0-tlast): Area under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Paclitaxel Time: Cycle 1, Day 15 pre-dose and up to 48 hours post-doseAllocation: Non-Randomized
Parallel Assignment
There is one SNP
Additional exclusion criteria for arm 5 only (MLN2480 + irinotecan): 1. Use of strong or moderate Cytochrome P4503A (CYP3A) inhibitors <= days of the first dose of irinotecan. --- P4503A ---