Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
TAK-659 · 2 trials · 4 indications
Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE), Version 5.0 DLT will be defined as any of the events specified in the protocol that are considered by the investigator to be at least possibly related to therapy with study medications and that occur within the first cycle.
AE Grades will be evaluated as per NCI CTCAE, version 5.0.
DLT was defined as one of the following adverse events considered by the investigator to be possibly related to study drug: Grade 4 neutropenia unresolved to ≤Grade 1 or baseline \>7 days in absence of growth factor support;≥Grade 3 neutropenia with fever and/or infection; Grade 4 thrombocytopenia unresolved to ≤ Grade 1 or baseline \>7 days or a platelet count \<10,000/mm\^3; ≥Grade 3 thrombocytopenia with clinically significant bleeding; Grade 4 anemia; ≥Grade 3 nonhematological toxicity except (nausea and/or vomiting or diarrhea that has not resolved after 48 hours of treatment, transient fatigue, asymptomatic lipase elevation in absence of amylase elevation, asymptomatic elevation of a single liver enzyme in absence of bilirubin elevation);Inability to administer at least 75% of planned doses of study drug within Cycle 1;TAK-659-related nonhematologic toxicities ≥Grade 2 that required dose reduction or therapy discontinuation.
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug. A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient 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.
| Arm | Type | Description |
|---|---|---|
| Dose Escalation: TAK-659 + Venetoclax | EXPERIMENTAL | TAK-659 40, 60, 80, or 100 milligram (mg) (tablet, orally, once daily, up to 35 days in Cycle 1 or in different intermittent schedules \[7 days dosing followed by 7 days off or 14 days dosing followed by 7 days off or other intermittent dosing schedules\]) along with venetoclax 200, 400, 800 or 1200 mg (tablet, orally, once daily, up to 35 days in Cycle 1). After Cycle 1, TAK-659 and venetoclax will be administered once daily in a 28-day treatment cycle until disease progression, unacceptable toxicities, or discontinuation by participant. |
| Safety Expansion: Diffuse Large B-cell Lymphoma (DLBCL) Cohort | EXPERIMENTAL | TAK-659 tablet, orally, once daily along with venetoclax tablet, orally, once daily in a 28-day treatment cycle until disease progression, unacceptable toxicities, or discontinuation by participant. TAK-659 and venetoclax MTD/RP2D will be determined from the dose escalation phase. |
| Safety Expansion: Follicular Lymphoma (FL) Cohort | EXPERIMENTAL | TAK-659 tablet, orally, once daily along with venetoclax tablet, orally, once daily in a 28-day treatment cycle until disease progression, unacceptable toxicities, or discontinuation by participant. TAK-659 and venetoclax MTD/RP2D will be determined from the dose escalation phase. |
| TAK-659 60 mg (Dose Escalation) | EXPERIMENTAL | TAK-659 60 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities (up to 49 cycles). |
| TAK-659 80 mg (Dose Escalation) | EXPERIMENTAL | TAK-659 80 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities (up to 4 cycles). |
| TAK-659 100 mg (Dose Escalation) | EXPERIMENTAL | TAK-659 100 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities (up to 32 cycles). |
| TAK-659 120 mg (Dose Escalation) | EXPERIMENTAL | TAK-659 120 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities (up to 41 cycles). |
| TAK-659 CCL (Dose Expansion) | EXPERIMENTAL | TAK-659 100 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities in participants with chronic lymphocytic leukemia (CCL) (up to 6 cycles). |
| TAK-659 DLBCL (Dose Expansion) | EXPERIMENTAL | TAK-659 100 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities in participants with diffuse large B-cell lymphoma (DLBCL) (up to 49 cycles). |
| TAK-659 iNHL (Dose Expansion) | EXPERIMENTAL | Single dose TAK-659 100 mg, tablet, orally in pharmacokinetic (PK) Run-in prior to Cycle 1 followed by TAK-659 100 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities in participants with indolent non-hodgkin lymphoma (iNHL) (up to 32 cycles). |
| TAK-659 MCL (Dose Expansion) | EXPERIMENTAL | TAK-659 100 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities in participants with mantle cell lymphoma (MCL) (up to 6 cycles). |
| TAK-659 PTLD (Dose Expansion) | EXPERIMENTAL | TAK-659 100 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities in participants with post-transplant lymphoproliferative disorder (PTLD) (up to 1 cycle). |
| Name | Type | Description |
|---|---|---|
| TAK-659 | DRUG | TAK-659 tablets. |
| Venetoclax | DRUG | Venetoclax tablets. |
Inclusion Criteria: 1. For the Dose Escalation phase, participants must have histologically confirmed diagnosis of advanced NHL of any histology (with the exception of participants with mantle cell lymphoma \[MCL\] or chronic lymphoma leukemia \[CLL\]). 2. For the Safety Expansion phase, participan...