A Phase 1b Study of TAK-659 in Combination With Venetoclax for Adult Patients With Previously Treated Non-Hodgkin Lymphoma
18 Years and older, Male and Female
The purpose of this study is to determine the maximum tolerated dose (MTD) and / or recommended phase 2 dose (RP2D) of TAK-659 and venetoclax when administered in combination in participants with non-Hodgkin lymphoma (NHL) relapsed and / or refractory after at least 1 prior line of therapy and to evaluate safety and tolerability of TAK-659 and venetoclax when administered in combination.
The drug being tested in this study is called TAK-659. TAK-659 in combination with venetoclax
is being tested to treat people who have advanced NHL after at least 1 prior line of therapy.
This study will look at the safety data, pharmacokinetic (PK) data and any early anti tumor
The study will enroll approximately 53 participants.
• TAK-659 and venetoclax doses will be escalated according to a Bayesian logistic regression
model (BLRM) with overdose control escalation schema. TAK-659 60 mg + Venetoclax 400 mg is
the starting dose.
Participants could also receive 20 mg, 40 mg, 80 mg or 100 mg TAK-659 during dose escalation.
Following dose escalation the safety and tolerability of the MTD/RP2D of the
TAK-659+venetoclax combination will be further explored in two dose-safety expansion cohorts,
Cohort 1 in participants with DLBCL and Cohort 2 in participants with FL.
All participants will be asked to take one tablet of TAK-659 on an empty stomach at least 1
hour before and no sooner than 2 hours after eating food and/or drinking fluids other than
water. Venetoclax will be taken with a meal and water 2 hours after TAK-659 has been taken.
No food or drink (except water) are allowed between TAK-659 and venetoclax. TAK-659 and
venetoclax should be taken at the same time each day throughout the study.
This multi-center trial will be conducted in the United States, Canada and Europe. The
overall time to participate in this study is 6 months or until disease progression,
unacceptable toxicities, or withdrawal from study by participant. Participants will make
multiple visits to the clinic, and will be followed for 28 days (+10) days after the last
dose of TAK-659 or venetoclax or the start of subsequent alternative anticancer therapy to
permit the detection of any delayed treatment-related AEs. 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 enrolled in the safety expansion part who stop treatment for any reason other
than disease progression (PD) will continue progression free survival (PFS) follow-up every 2
months after the last dose of study drug for up to 6 months or until PD or the start of
alternative therapy, whichever occurs first.