First-in-Human Study of TAK-280 in Participants With Solid Tumors
- Conditions
- Unresectable Locally Advanced or Metastatic Cancer
- Interventions
- Drug: TAK-280
- Registration Number
- NCT05220098
- Lead Sponsor
- Takeda
- Brief Summary
The main aim of this study is to find out the safety, tolerability, and effect of TAK- 280 in participants with unresectable, locally advanced or metastatic cancer who have experienced treatment failure or are intolerant to standard therapies.
Participants will be treated with TAK-280 for up to 14 treatment cycles. Each treatment cycle will be 28 days.
After the last dose of study drug, participants will be followed up for survival every 12 weeks for a total of 48 weeks.
- Detailed Description
This study consists of 2 phases: Dose-escalation and cohort-expansion phase.
Dose-escalation phase:
The purpose of the dose-escalation phase is to generate data to characterize the initial safety and tolerability profile of TAK-280 and determine the 2 recommended doses for expansion (RDEs) of TAK-280 to be administered during the cohort-expansion phase.
Cohort-Expansion Phase:
The cohort expansion phase will be conducted in 3 indications. Only in 1 selected indication participants will be randomized 1:1 to receive either TAK-280 high dose or low dose. In the remaining 2 indications to be studied in the cohort-expansion phase, participants will receive only one dose level of TAK-280.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 182
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose-escalation Phase: TAK-280 TAK-280 Participants will receive TAK-280 intravenous (IV) infusion on Days 1, 8, 15, and 22 of a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal from study occurs. Cohort-expansion Phase: TAK-280 High or low Dose TAK-280 Participants will receive either TAK-280 high or low dose in one selected indication and only one dose level of TAK-280 in the remaining indications as determined from the dose-escalation phase of the study in 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal from study occurs.
- Primary Outcome Measures
Name Time Method Number of Participants With Dose Limiting Toxicities (DLTs) From start of the initial dose up to Cycle 1 Day 28 DLT evaluation period is defined as the time between the initial dose of TAK-280 and Cycle 1 Day 28.
Number of Participants With Treatment- emergent Adverse Events (TEAEs) Up to approximately 37 months
- Secondary Outcome Measures
Name Time Method Area Under Plasma Concentration-Time Curve (AUC) of TAK- 280 Pre-dose and at multiple time points post-dose on Days 1, 2, 3, 8, 15, 22 up to the end of treatment (Up to 14 months) AUC of TAK-280 will be reported.
Time to Reach Maximum Observed Plasma Concentration (tmax) of TAK-280 Pre-dose and at multiple time points post-dose on Days 1, 2, 3, 8, 15, 22 up to the end of treatment (Up to 14 months) tmax of TAK-280 will be reported.
Disease Control Rate Up to approximately 37 months Disease control rate is defined as the percentage of participants who achieve PR or CR or SD, with a duration of greater than or equal to (\>=) 2 consecutive scans.
Total Clearance (CL) of TAK-280 Pre-dose and at multiple time points post-dose on Days 1, 2, 3, 8, 15, 22 up to the end of treatment (Up to 14 months) CL of TAK-280 will be reported.
Confirmed Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST V1.1) Up to approximately 37 months ORR is defined as the percentage of participants who achieve confirmed complete response (CR) or partial response (PR) based on RECIST V1.1 as determined by the investigator during the study.
Progression Free Survival (PFS) From start of first dose to disease progression or death, whichever occurred first (up to approximately 37 months) PFS is defined as the time from the date of the first dose of TAK-280 to the date of first documentation of PD or death due to any cause, whichever occurs first.
Duration of PSA Response in Participants With mCRPC Up to approximately 37 months Duration of PSA response is defined as the time from first PSA response to first documented PSA progression.
Percentage of Participants who Develop Positive Induced Antidrug Antibody (ADA) for TAK-280 Cycle 1 to 5: pre-dose (Each cycle= 28 days) Percentage of Participants who Developed Neutralizing Antibody (NAb) Titers for TAK-280 Cycle 1 to 5: pre-dose (Each cycle= 28 days) Maximum Observed Plasma Concentration (Cmax) of TAK-280 Pre-dose and at multiple time points post-dose on Days 1, 2, 3, 8, 15, 22 up to the end of treatment (Up to 14 months) Cmax of TAK-280 will be reported.
Duration of Response (DOR) Based on RECIST V1.1 Up to approximately 37 months DOR is defined as the time from the date of first documentation of a PR or better to the date of first documentation of progressive disease (PD) or death due to any cause, whichever occurs first, for participants with a confirmed response (PR or better).
Percentage of Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) Having Prostate-Specific Antigen (PSA) Response Up to approximately 37 months PSA response is defined as PSA reduction from baseline of \>= 50 percent (%) and confirmed at least 3 weeks later.
Time to PSA Progression in Participants With mCRPC Up to approximately 37 months Time to PSA progression is defined as the time from the date of first dose of TAK-280 to the date that an increase of 25% or more and absolute increase of 2 nanograms/milliliter (ng/mL) or more from the nadir.
Percentage of Participants With mCRPC Having PSA Reductions of >= 50% up to 6 Months Baseline up to 6 months Terminal Disposition Phase Half-Life (t1/2) of TAK-280 Pre-dose and at multiple time points post-dose on Days 1, 2, 3, 8, 15, 22 up to the end of treatment (Up to 14 months) t1/2 of TAK-280 will be reported.
Volume of Distribution at Steady State (Vss) After IV Administration of TAK-280 Pre-dose and at multiple time points post-dose on Days 1, 2, 3, 8, 15, 22 up to the end of treatment (Up to 14 months) Vss of TAK-280 will be reported.
Overall Survival (OS) From start of first dose of study drug up to death (up to approximately 37 months) OS is defined as the time from the date of the first dose of TAK-280 to the date of death due to any cause.
Trial Locations
- Locations (24)
Duke Cancer Institute
🇺🇸Durham, North Carolina, United States
University of Arkansas For Medical Sciences
🇺🇸Little Rock, Arkansas, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
University of Minnesota - Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Sanford Cancer Center
🇺🇸Sioux Falls, South Dakota, United States
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
SCRI Tennessee Oncology Nashville
🇺🇸Nashville, Tennessee, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Froedtert and The Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Chris O'Brien Lifehouse Hospital
🇦🇺Camperdown, New South Wales, Australia
Southern Oncology Clinical Research Unit
🇦🇺Bedford Park, Australia
Monash Medical Centre
🇦🇺Clayton, Australia
Cabrini Health
🇦🇺Malvern, Australia
Centre Intégré de Cancérologie du CHU de Québec - Université Laval
🇨🇦Quebec, Canada
Centre Hospitalier Universitaire de Sherbrooke CHUS
🇨🇦Sherbrooke, Canada
Princess Margaret Hospital
🇨🇦Toronto, Canada
Hospital Quironsalud Barcelona, NEXT Oncology
🇪🇸Barcelona, Spain
Hospital Universitari Dexeus - Grupo Quironsalud
🇪🇸Barcelona, Spain
Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON
🇪🇸Barcelona, Spain
START MADRID_Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Virgen de la Victoria
🇪🇸Malaga, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain