This study is an open-label, multicenter, phase 1, dose escalation study of TAK-659 in adult participants with advanced solid tumor and lymphoma malignancies. This study will be the first to administer TAK-659 to humans. The participants population during dose escalation (Part A) will consist of adults previously diagnosed with any form of a solid tumor or lymphoma for which standard, curative, or life-prolonging treatment does not exist or is no longer effective. This first-in-human (FIH) study will include 5 dose expansion cohorts in refractory and/or relapsed Chronic Lymphocytic Leukemia (CLL), Diffuse Large B Cell Lymphoma (DLBCL), indolent Non Hodgkin Lymphoma (iNHL), Mantle Cell Lymphoma (MCL), Post Transplant Lymphoproliferative Disorder (PTLD) (Part B) following completion of dose escalation (Part A).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
143
TAK-659 tablet
Florida Cancer Specialists, Sarasota FL
Sarasota, Florida, United States
Northwestern University
Chicago, Illinois, United States
SCRI
Nashville, Tennessee, United States
The Methodist Hospital Research Institute
Houston, Texas, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States
Azienda Ospedaliera Papa Giovanni XXIII
Bergamo, Italy
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi
Bologna, Italy
Ospedale San Raffaele U.O. di Ematologia e Trapianto di midollo osseo
Milan, Italy
Azienda Ospedaliera Universitaria Policlinico Tor Vergata
Roma, Italy
Hospital Universitari Vall d'Hebron
Barcelona, Spain
...and 5 more locations
Percentage of Participants with Dose Limiting toxicities (DLTs) in Cycle 1
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.
Time frame: 28-day Cycle
Number of participants with Adverse events (AEs), Grade 3 and 4 AEs, Serious Adverse events (SAEs), Discontinuations for AEs
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.
Time frame: First dose of study drug through 28 days after the last dose of study drug (Up to 49 months )
Overall response rate (ORR) in the CLL, DLBCL, iNHL, MCL, and PTLD Cohorts
Time frame: Start of study drug treatment through Days 22 to 29 of Cycles 2,at end of every even numbered Cycle through 12,at end of every 4cycles through 24,at end of every 6 Cycles thereafter until disease progression or start of alternative therapies,End of Study
Duration of response (DOR), time to progression (TTP) and progression-free survival (PFS) in the CLL, DLBCL, iNHL, MCL, PTLD Cohorts
Time frame: Start of study drug treatment through Days 22 to 29 of Cycles 2, even numbered Cycle through 12,and at the end of every 4 cycles through 24, at the end of every 6 Cycles thereafter until disease progression or start of alternative therapies, End of Study
Overall Survival (OS) Rate in the CLL, DLBCL, iNHL, MCL, PTLD Cohorts
Time frame: Start of study drug treatment through last dose of study drug, then every 3 months until 12 months after first dosing of study drug if applicable, death, or the conclusion of the study, whichever occurs first (total duration of assessment up to 1 year)
Cmax: Maximum Observed Plasma Concentration for TAK-659
Time frame: Dose escalation: Cycle 1 Days 1 and 15 predose and multiple timepoints up to 24 hours postdose; PK Run-in Phase of the indolent NHL expansion cohort: predose and multiple timepoints up to 168 hours after a single dose prior to Cycle 1 Day 1
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659
Time frame: Dose escalation: Cycle 1 Days 1 and 15 predose and multiple timepoints up to 24 hours postdose; PK Run-in Phase of the indolent NHL expansion cohort: predose and multiple timepoints up to 168 hours after a single dose prior to Cycle 1 Day 1
AUC(0-24): Area under the Plasma Concentration-Time Curve from Time 0 to Time 24 hour for TAK-659
Time frame: Dose escalation: Cycle 1 Days 1 and 15 predose and multiple timepoints up to 24 hours postdose; PK Run-in Phase of the indolent NHL expansion cohort: predose and multiple timepoints up to 168 hours after a single dose prior to Cycle 1 Day 1
AUClast: Area under the Plasma Concentration-Time Curve from Time 0 to Time of the Last Quantifiable Concentration for TAK-659
Time frame: Dose escalation: Cycle 1 Days 1 and 15 predose and multiple timepoints up to 24 hours postdose; PK Run-in Phase of the indolent NHL expansion cohort: predose and multiple timepoints up to 168 hours after a single dose prior to Cycle 1 Day 1
T1/2: Terminal Disposition Half-life
Time frame: Dose escalation: Cycle 1 Days 1 and 15 predose and multiple timepoints up to 24 hours postdose; PK Run-in Phase of the indolent NHL expansion cohort: predose and multiple timepoints up to 168 hours after a single dose prior to Cycle 1 Day 1
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.