The purpose of this study is to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) for TAK-659 when administered in combination with NKTR-214.
The drugs that are being tested in this study are TAK-659 and NKTR-214. TAK-659 in combination with NKTR-214 is being tested for participants with advanced B-cell NHL, including DLBCL, FL, MZL, or MCL, after 2 prior lines of therapy. The study will determine the MTD or the RP2D of TAK-659 when administered with NKTR-214. The study will enroll approximately 40 participants, approximately 18 to 24 participants in a dose escalation phase, and approximately 12 participants will be added after determination of MTD/RP2D in the safety expansion phase. This study consists of 2 phases: a dose escalation phase and a safety expansion phase. TAK-659 and NKTR-214 doses will be escalated according to a modified 3+3 dose escalation schema. TAK-659 60 milligram (mg) + NKTR-214 0.003 milligram per kilogram (mg/kg) is the starting dose. Participants could also receive 80 mg once daily (QD) TAK-659 during dose escalation and 0.003mg/kg or 0.006mg/kg of NKTR-214. Lower doses (example 40 mg) and/or alternative regimens (including intermittent dosing) or schedules of TAK-659 are permissible following discussion between sponsor and investigators. In dose escalation phase, dose levels will be escalated based on available safety and tolerability data to determine the MTD or RP2D. Dose for safety expansion phase will be based on available safety, pharmacodynamics, and preliminary efficacy data. For participants enrolled in either the dose escalation or safety expansion phases, the maximum duration of treatment will be 12 months unless, in the opinion of the investigator and with the agreement of the sponsor, the participant would derive benefit from continued therapy beyond 12 months. Participants will make multiple visits to the clinic, and will have an end of treatment visit 30 days after the last dose of TAK-659 or NKTR-214 or before the start of subsequent alternative anticancer therapy, whichever occurs first. Participants will be followed for 90 days after the last dose or subsequent anti-cancer therapy, whichever occurs first, to permit the detection of any delayed treatment-related adverse events (AEs).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
University of Alabama at Birmingham
Birmingham, Alabama, United States
Henry Ford Hospital
Detroit, Michigan, United States
New York University Langone Medical Center
New York, New York, United States
Alberta Health Services
Calgary, Alberta, Canada
MTD of TAK-659 in Combination with NKTR-214
Time frame: 3 weeks after last dose of last participant in dose escalation or up to 6 months
RP2D of TAK-659 in Combination with NKTR-214
Time frame: 3 weeks after last dose of last participant in dose escalation or up to 6 months
Cmax: Maximum Observed Plasma Concentration for TAK-659
Time frame: Cycle 1 and Cycle 2: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (cycle length=21 days)
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659
Time frame: Cycle 1 and Cycle 2: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (cycle length=21 days)
AUCτ: Area Under the Plasma Concentration-time Curve From Time During the Dosing Interval for TAK-659
Time frame: Cycle 1 and Cycle 2: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (cycle length=21 days)
Cmax: Maximum Observed Plasma Concentration for NKTR-214
Time frame: Cycle 1 Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (cycle length=21 days)
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for NKTR-214
Time frame: Cycle 1 Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (cycle length=21 days)
AUC: Area Under the Plasma Concentration-time Curve for NKTR-214
Time frame: Cycle 1 Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (cycle length=21 days)
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Jewish General Hospital
Montreal, Quebec, Canada
Centre Hospitalier Universitaire de Sherbrooke (CIUSSS de lEstrie - CHUS)
Sherbrooke, Quebec, Canada
Overall Response Rate (ORR)
ORR is defined as the percentage of participants in the response-evaluable population who achieved either complete response (CR) or partial response (PR) as assessed by the investigator according to the Lugano 2014 criteria.
Time frame: Through study completion, approximately 40 months
Duration of Response (DOR)
DOR is defined as the time from first CR or PR to PD or relapse in the response-evaluable population.
Time frame: From first CR or PR to progressive disease (PD) or relapse (through study completion, approximately 40 months)
Progression-free Survival (PFS)
PFS is defined as the time from first dose to PD or death in the response-evaluable population.
Time frame: From first dose of study drug to PD or death (through study completion, approximately 40 months)