The purpose of this study is to evaluate the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D), safety and efficacy of TAK-659 in combination with nivolumab in participants with advanced solid tumors.
The drug being tested is TAK-659.This study will look at the determination of the MTD/RP2D and efficacy measured by ORR in participants who take TAK-659 in combination with nivolumab. The study will include a dose escalation phase (Part 1), a potential nivolumab fixed dose cohort, and a dose expansion phase (Part 2). The study will enroll approximately 120 participants, approximately 9-12 in the dose escalation phase and approximately 36 in each of the 3 dose expansion cohorts. Participants will be assigned to 1 of the 4 treatment groups: * Part 1: Advanced Solid Tumors * Potential Nivolumab Fixed Dose Cohort * Part 2: Metastatic TNBC * Part 2: Metastatic NSCLC * Part 2: Metastatic HNSCC All participants will be asked to take the tablets of TAK-659 at the same time each day throughout the study. Participants will also receive intravenous infusion of nivolumab (within 30 minutes after the TAK-650 dose) once every 2 weeks. This multi-center trial will be conducted globally. The overall time to receive treatment in this study is approximately 12 months. Participants will be assessed for disease response and PD during the PFS follow-up of 6 months (for participants who discontinue due to reasons other than PD) and OS follow-up of 12 months from the last dose of study drug.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
41
UCSD
La Jolla, California, United States
Part 1, Dose Escalation Phase: Maximum Tolerated Dose (MTD)
The MTD was defined as the dose range at which less than or equal to (\<=) 1 of 6 evaluable participants experience dose limiting toxicities (DLT) within the first 28 days of treatment (end of Cycle 1). Toxicities were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
Time frame: At end of Cycle 1 Day 28
Part 1, Dose Escalation Phase: Recommendation Phase 2 Dose (RP2D)
RP2D was evaluated from cumulative toxicities in Cycle 1 and beyond. Toxicities were evaluated according to NCI CTCAE version 4.03.
Time frame: Up to Cycle 12 (each Cycle length is equal to [=] 28 days)
Part 2, Dose Expansion Phase: Overall Response Rate (ORR)
ORR was defined as the percentage of participants who's best overall response (BOR) was either complete response (CR) or partial response (PR). The ORR assessment was based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The BOR was defined as the best response recorded from the start of the study treatment until the start of subsequent anticancer therapy. CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (\<) 10 millimeter (mm). PR: was at least a 30 percent (%) decrease in sum of diameter (SOD) of target lesions, taking as reference the baseline SOD.
Time frame: From the start of study treatment until the start of subsequent anticancer therapy (up to 28 months)
Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Events (TEAEs), Grade 3 or 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation
AEs Grades were evaluated as per NCI CTCAE version 4.03.
Time frame: From the first dose of the study drug up to 28 days after the last dose of the study drug or the start of subsequent anticancer therapy (up to 28 months)
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Emory
Atlanta, Georgia, United States
Massachusetts General
Boston, Massachusetts, United States
Barbara Ann Karmanos
Detroit, Michigan, United States
Roswell Park
Buffalo, New York, United States
Fox Chase
Philadelphia, Pennsylvania, United States
Vanderbilt
Nashville, Tennessee, United States
Mary Crowley Research Centers
Dallas, Texas, United States
US Oncology
Fairfax, Virginia, United States
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) S.r.l
Meldola, Italy
...and 12 more locations
Part 2, Dose Expansion Phase: Disease Control Rate (DCR)
DCR was the percentage of participants who had BOR with either CR, PR, or stable disease (SD). The DCR assessment was based on RECIST version 1.1. The BOR was defined as the best response recorded from the start of the study treatment until the start of subsequent anticancer therapy. CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to \<10 mm. PR: was at least a 30% decrease in SOD of target lesions, taking as reference the baseline SOD. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD.
Time frame: From the start of study treatment until the start of subsequent anticancer therapy (up to 28 months)
Part 2, Dose Expansion Phase: Duration of Response (DOR)
DOR was defined as the time from the date of first documentation of a response to the date of first documented progressive disease. DOR assessment was based on RECIST v1.1. CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to \<10 mm. PR: at least 30% decrease in SOD of target lesions, taking as reference the baseline SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. DOR was calculated using Kaplan-Meier analysis.
Time frame: From the date of first documentation of a response to the date of first documented PD (up to 28 months)
Part 2, Dose Expansion Phase: Percentage of Participants With PD at Month 6
PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. The PD assessment was based on RECIST v1.1.
Time frame: Month 6
Part 2, Dose Expansion Phase: Progression Free Survival (PFS)
PFS was defined as the time from date of first study drug administration to the date of first documented PD or death due to any cause, whichever occurred first. The PFS assessment was based on RECIST v1.1. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. PFS was calculated using Kaplan-Meier estimate.
Time frame: From the date of first study drug administration up to date of first documented PD or death due to any cause, whichever occurred first (up to 28 months)
Part 2, Dose Expansion Phase: Overall Survival (OS)
OS was calculated from date of participant enrollment to the date of participant's death due to any cause. OS was assessed based on RECIST v 1.1. Participants without documentation of death at time of the analysis were censored as of the date the participant was last known to be alive, or the data cutoff date, whichever was earlier. OS was calculated using Kaplan-Meier estimate. Enrollment was defined as the time of the initiation of the first dose of study drug.
Time frame: Baseline up to the date of death due to any cause (up to 28 months)
Part 1, Dose Escalation Phase, Cmax: Maximum Observed Plasma Concentration for TAK-659
Time frame: Cycle 1, Days 1 and 15: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)
Part 1, Dose Escalation Phase, Tmax: Time to Reach the Cmax for TAK-659
Time frame: Cycle 1, Days 1 and 15: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)
Part 1, Dose Escalation Phase, AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 to Tau Over the Dosing Interval for Area Under the Plasma Concentration for TAK-659
Time frame: Cycle 1, Days 1 and 15: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)