The purpose of this study is to determine the safety, tolerability, maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of TAK-659 when administered in East Asian participants with NHL who do not have an effective standard treatment available and to characterize the plasma and urine pharmacokinetic (PK) of TAK-659 in East Asian participants with NHL.
The drug being tested in this study is called TAK-659. TAK-659 is being tested to treat people who have NHL or people who have relapsed and/or refractory NHL. This study will assess the safety, tolerability, PK, and preliminary efficacy of single-agent TAK-659 in East Asian participants with NHL. The study will enroll approximately 33 to 47 participants, including at least 6 Japanese at RP2D dose level. Participants will be assigned to one of the following treatment groups: Dose Escalation Part: TAK-659 Expansion Part: TAK-659 RP2D This multi-center trial will be conducted in Japan and Republic of Korea. The maximum duration of participation in dose escalation part of the study is up to 12 months, unless in the opinion of the investigator and sponsor the participant would derive benefit from continued therapy beyond 12 months. In expansion part, participants who stop treatment for any other reason other than PD will continue to have PFS follow-up at the site every 2 months from the last dose of study drug up to 6 months or until PD. Participants will be followed 28 days after last dose of study drug or until the start of subsequent antineoplastic therapy, whichever occurs first, for a follow up assessment.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
17
TAK-659 Tablets.
NHO Nagoya Medical Center
Nagoya, Aichi-ken, Japan
National Cancer Center Hospital
Chuo-ku, Tokyo, Japan
Seoul National University Hospital
Seoul, South Korea
Samsung Medical Center
Seoul, South Korea
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days)
Percentage of Participants With Grade 3 or Higher TEAEs
TEAEs were graded as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03. As per the NCI-CTCAE, Grade 1 (mild, asymptomatic or mild symptoms); Grade 2 (moderate, minimal, local or noninvasive intervention indicated); Grade 3 (severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (life-threatening consequences, urgent intervention indicated); Grade 5 (death related to adverse event \[AE\]).
Time frame: From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days)
Percentage of Participants With Serious TEAEs
Time frame: From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days)
Dose Escalation Part: Percentage of Participants With Dose-limiting Toxicities (DLTs) During Cycle 1
DLT was evaluated as per NCI-CTCAE, v4.03 and defined as any of the following events occurring during Cycle 1 that were considered by the investigator to be possibly related to therapy: Grade 4 neutropenia unresolved to less than or equal to (\<=) Grade 1 or baseline for more than 7 days in the absence of growth factor support; greater than or equal to (\>=) Grade 3 neutropenia with fever and/or infection;Grade 4 thrombocytopenia unresolved to \<=Grade 1 or baseline for more than 7 days; \>=Grade 3 thrombocytopenia with clinically significant bleeding; Grade \>=3 nonhematologic toxicity except for treated \>=Grade 3 nausea and/or emesis and diarrhea resolved to less than (\<) Grade 3 within 3 days, Grade 3 fatigue \<=72 hours, isolated asymptomatic \>=Grade 3 laboratory abnormalities resolved to \<=Grade 1 or baseline in \<=7 days;received \<75% of planned doses of study drug in Cycle 1;TAK-659-related \>=Grade 2 nonhematologic toxicities that required dose reduction or discontinuation of therapy.
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Time frame: Cycle 1 (Cycle length =28 days)
Percentage of Participants Who Discontinued Study Drug Due to TEAEs
Time frame: From first dose of study drug up to 28 days after the last dose of study drug or before the start of subsequent anticancer therapy (up to Cycle 31) (Cycle length =28 days)
Cmax: Maximum Observed Plasma Concentration for TAK-659 on Cycle 1 Day 1
Time frame: Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)
Cmax: Maximum Observed Plasma Concentration for TAK-659 on Cycle 1 Day 7 (Dosing Schedule B) and Cycle 1 Day 15 (Dosing Schedule A)
Time frame: Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A): pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659 on Cycle 1 Day 1
Time frame: Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659 on Cycle 1 Day 7 (Dosing Schedule B) and Cycle 1 Day 15 (Dosing Schedule A)
Time frame: Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A): pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)
AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-659 on Cycle 1 Day 1
Time frame: Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)
AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-659 on Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A)
Time frame: Cycle 1 Day 7 (Dosing Schedule B) and Day 15 (Dosing Schedule A): pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)
CLR: Renal Clearance for TAK-659 on Cycle 1 Day 15
Time frame: Cycle 1 Day 15: pre-dose and at multiple time points (up to 8 hours) post-dose (Cycle length= 28 days)