Unresectable Locally Advanced or Metastatic Cancer
Conditions
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.
Interventions
DRUGTAK-280
Participants will receive TAK-280 as IV infusion.
Sponsors
Takeda
Takeda Development Center Americas, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose-escalation Phase is non-randomized and Cohort-expansion Phase will include randomized and non-randomized cohorts.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age greater than or equal to (\>=)18 years or \>= the local legal age of majority, as applicable. * Criteria for disease state in dose escalation and cohort expansion. 1. Tumor histologies during dose escalation: Dose escalation will begin by initially enrolling participants with histologically or pathologically confirmed, unresectable, locally advanced or metastatic cancers. 2. Tumor histologies during cohort expansion: Participants will be eligible if they have histologically proven, unresectable, locally advanced or metastatic malignant neoplasms. * Eastern Cooperative Oncology Group performance status (less than or equal to \[\<=\]) 1. * Measurable disease per RECIST V1.1 by investigator except for participants with mCRPC with bone metastases only (these participants are allowed in the study). Lesions in previously irradiated areas (or other local therapy) should not be selected as measurable/target lesions, unless treatment was \>=6 months prior to start of treatment or there has been demonstrated progression with a clear margin to measure in that particular lesion.
Exclusion criteria
* History of known autoimmune disease. * Major surgery or traumatic injury within 8 weeks before the first dose of TAK-280. * Unhealed wounds from surgery or injury. * Ongoing or active infection of Grade \>=2. * Oxygen saturation less than (\<) 92 percent (%) on room air at screening or during Cycle 1 Day 1 (C1D1) predose assessment. * Inflammatory process that has not resolved for \>= 4 weeks before the first dose of study drug. Participants with chronic low-grade inflammatory processes such as radiation-induced pneumonitis are excluded regardless of their duration. * Vaccination with any live virus vaccine within 4 weeks or other vaccines within 2 weeks before the initiation of study drug administration. Inactivated annual influenza vaccination is allowed. * Known hypersensitivity to TAK-280 or any excipient.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | Cycle 1 (Cycle length=28 days) | DLTs were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0, except cytokine release syndrome (CRS), which was graded according to American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading for CRS. |
| Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs) | From start of study drug administration up to follow-up (up to 37 weeks) | An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE was defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of new anticancer therapy. AEs were evaluated according to NCI CTCAE, Version 5.0 except CRS, which was graded according to ASTCT Consensus Grading for CRS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of TAK-280 | Cycles 1-7: Pre-dose and post-dose up to 48 hours on Days 1, 2, 3, 8, 15 and 22 (Cycle length= 28 days) | Cmax for TAK-280 was reported. |
| Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUC0-last) of TAK- 280 | Cycles 1-7: Pre-dose and post-dose up to 48 hours on Days 1, 2, 3, 8, 15 and 22 (Cycle length= 28 days) | AUC0-last for TAK-280 was reported. |
| Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of TAK-280 | Cycles 1-7: Pre-dose and post-dose up to 48 hours on Days 1, 2, 3, 8, 15 and 22 (Cycle length= 28 days) | AUC0-inf for TAK-280 was reported. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of TAK-280 | Cycles 1-7: Pre-dose and post-dose up to 48 hours on Days 1, 2, 3, 8, 15 and 22 (Cycle length= 28 days) | Tmax for TAK-280 was reported. |
| Terminal Disposition Phase Half-Life (t1/2) of TAK-280 | Cycles 1-7: Pre-dose and post-dose up to 48 hours on Days 1, 2, 3, 8, 15 and 22 (Cycle length= 28 days) | T1/2 was reported. |
| Total Clearance (CL) of TAK-280 | Cycles 1-7: Pre-dose and post-dose up to 48 hours on Days 1, 2, 3, 8, 15 and 22 (Cycle length= 28 days) | CL of TAK-280 was reported. |
| Volume of Distribution at Steady State (Vss) After IV Administration of TAK-280 | Cycles 1-7: Pre-dose and post-dose up to 48 hours on Days 1, 2, 3, 8, 15 and 22 (Cycle length= 28 days) | Vss of TAK-280 was reported. |
| Overall Response Rate (ORR) | Up to 37 weeks | ORR was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Prostate Cancer Working Group 3 (PCWG3) as defined by the Investigator based on radiologic criteria. ORR was defined as the percentage of participants who achieved complete response (CR) or partial response (PR) as per RECIST version 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeter (mm). PR: At least a 30 percentage (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Duration of Response (DOR) | Up to 37 weeks | The DOR was assessed according to RECIST version 1.1. and defined as time from the date of first documentation of a PR or better to the date of the first documentation of progressive disease (PD) or death due to any cause, whichever occurred first, for participants with a confirmed response (PR or better). CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Progression Free Survival (PFS) | Up to 37 weeks | PFS was assessed according to RECIST version 1.1 and was defined as the time from the date of first dose of TAK-280 to the date of first documentation of PD or death due to any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum diameters while on study. |
| Overall Survival (OS) | Up to 37 weeks | OS was defined as the time from the date of first dose TAK-280 until death due to any cause. |
| Disease Control Rate (DCR) | Up to 37 weeks | DCR was defined as the percentage of participants who achieved PR, CR, or stable disease (SD) with a duration of \>=2 consecutive scans determined by the investigator as per RECIST v1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. |
| Number of Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) Having Prostate-Specific Antigen (PSA) Response | Up to 37 weeks | PSA response was defined as a reduction in baseline PSA level of greater than or equal to (\>=) 50% maintained for at least 3 weeks in participants with mCRPC. |
| Duration of PSA Response in Participants With mCRPC | Up to 37 weeks | Duration of PSA response was the time from the date of the first PSA response to the date of the first documented PSA progression in participants with mCRPC. |
| Time to PSA Progression in Participants With mCRPC | Up to 37 weeks | Time to PSA progression was the time from the date of the first dose of TAK-280 to the date that an increase of 25% or more and absolute increase of 2 ng/mL or more from the nadir in participants with mCRPC. |
| Percentage of Participants With PSA Reductions of >=50% at 6 Months | At 6 months | PSA response was defined as a reduction in baseline PSA level of \>=50% maintained for at 6 months in participants with mCRPC. |
| Number of Participants Who Develop Positive Induced Antidrug Antibody (ADA) for TAK-280 | Up to 37 weeks | Number of participants who were negative for TAK-280 at baseline and became positive were reported. |
| Number of Participants Who Developed B7-H3 Targeted Neutralizing Antibodies (NAb) to TAK 280 | Up to 37 weeks | Number of participants who developed B7-H3 NAb titers for TAK-280 were reported. TAK-280 is a bispecific T-cell engager with binding specificity for B7-H3 and conditional binding to CD3. |
| Number of Participants Who Developed CD3 Targeted Neutralizing Antibodies to TAK 280 | Up to 37 weeks | Number of participants who developed CD3 NAb titers for TAK-280 were reported. TAK-280 is a bispecific T-cell engager with binding specificity for B7-H3 and conditional binding to CD3. |
Countries
Australia, Canada, Spain, United States
Contacts
STUDY_DIRECTORStudy Director
Takeda
Participant flow
Recruitment details
Participants took part in 20 investigative sites in the United States, Australia, Canada, and Spain from 21 April 2022 to 28 July 2025.
Pre-assignment details
A total of 69 participants were enrolled and received study treatment in the dose-escalation phase. The study was terminated early by the sponsor due to the limited anti-cancer activity observed with TAK-280 during dose-escalation phase. Dosing information (dosage strengths) has not been disclosed as it is considered as company confidential information (CCI). Dose levels are presented as Dose levels A to J. The study ended early, so only dose-escalation phase was conducted.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 61.3 years STANDARD_DEVIATION 9.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 62 Participants |
| Sex: Female, Male Female | 37 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 2 | 1 / 1 | 1 / 3 | 3 / 5 | 3 / 5 | 5 / 5 | 7 / 8 | 6 / 12 | 5 / 26 | 1 / 2 |
| other Total, other adverse events | 2 / 2 | 1 / 1 | 3 / 3 | 5 / 5 | 5 / 5 | 5 / 5 | 8 / 8 | 12 / 12 | 26 / 26 | 2 / 2 |
| serious Total, serious adverse events | 2 / 2 | 0 / 1 | 1 / 3 | 4 / 5 | 4 / 5 | 4 / 5 | 6 / 8 | 8 / 12 | 14 / 26 | 2 / 2 |
Outcome results
None listed