First-in-Human Study of TAK-280 in Participants With Solid Tumors

A Phase 1/2, First-in-Human, Open-Label, Dose-Escalation Study of TAK-280 in Patients With Unresectable Locally Advanced or Metastatic Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Unresectable Locally Advanced or Metastatic Cancer
• Intervention / Treatment: Drug: TAK-280

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.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Bedford Park, Australia, 5042
    • Southern Oncology Clinical Research Unit
  • Clayton, Australia, 3168
    • Monash Medical Centre
  • Malvern, Australia, 3144
    • Cabrini Health
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Chris O'Brien Lifehouse Hospital
• Canada
  • Québec, Canada, G1J 1Z4
    • Centre intégré de cancérologie du CHU de Québec - Université Laval
  • Sherbrooke, Canada, J1H 5N4
    • Centre Hospitalier Universitaire de Sherbrooke CHUS
• Spain
  • Barcelona, Spain, 08028
    • Hospital Universitari Dexeus - Grupo Quironsalud
  • Barcelona, Spain, 08023
    • Hospital Quironsalud Barcelona, NEXT Oncology
  • Barcelona, Spain, 08035
    • Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28040
    • START MADRID_Hospital Universitario Fundacion Jimenez Diaz
  • Málaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • San Francisco, California, United States, 94143
      • University of California San Francisco
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota - Masonic Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Institute
  • Ohio
    • Cleveland, Ohio, United States, 44195-0001
      • The Cleveland Clinic Foundation
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
    • Sioux Falls, South Dakota, United States, 57104-8805
      • Sanford Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • SCRI Tennessee Oncology Nashville
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert and The Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose-escalation Phase: 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.	Drug: TAK-280; Participants will receive TAK-280 as IV infusion.
Experimental: Cohort-expansion Phase: TAK-280 High or low Dose; 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.	Drug: TAK-280; Participants will receive TAK-280 as IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose Limiting Toxicities (DLTs)	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.	Cycle 1 (Cycle length=28 days)
Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs)	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.	From start of study drug administration up to follow-up (up to 37 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of TAK-280	Cmax for TAK-280 was reported.	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)
Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUC0-last) of TAK- 280	AUC0-last for TAK-280 was reported.	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)
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of TAK-280	AUC0-inf for TAK-280 was reported.	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)
Time to Reach Maximum Observed Plasma Concentration (Tmax) of TAK-280	Tmax for TAK-280 was reported.	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)
Terminal Disposition Phase Half-Life (t1/2) of TAK-280	T1/2 was reported.	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)
Total Clearance (CL) of TAK-280	CL of TAK-280 was reported.	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)
Volume of Distribution at Steady State (Vss) After IV Administration of TAK-280	Vss of TAK-280 was reported.	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)
Overall Response Rate (ORR)	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.	Up to 37 weeks
Duration of Response (DOR)	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.	Up to 37 weeks
Progression Free Survival (PFS)	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.	Up to 37 weeks
Overall Survival (OS)	OS was defined as the time from the date of first dose TAK-280 until death due to any cause.	Up to 37 weeks
Disease Control Rate (DCR)	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.	Up to 37 weeks
Number of Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) Having Prostate-Specific Antigen (PSA) Response	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.	Up to 37 weeks
Duration of PSA Response in Participants With mCRPC	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.	Up to 37 weeks
Time to PSA Progression in Participants With mCRPC	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.	Up to 37 weeks
Percentage of Participants With PSA Reductions of >=50% 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.	At 6 months
Number of Participants Who Develop Positive Induced Antidrug Antibody (ADA) for TAK-280	Number of participants who were negative for TAK-280 at baseline and became positive were reported.	Up to 37 weeks
Number of Participants Who Developed B7-H3 Targeted Neutralizing Antibodies (NAb) to TAK 280	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.	Up to 37 weeks
Number of Participants Who Developed CD3 Targeted Neutralizing Antibodies to TAK 280	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.	Up to 37 weeks

Collaborators and Investigators

• Sponsor: Takeda
• Collaborators: Takeda Development Center Americas, Inc.
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

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• Click here for more information about this trial in easy-to-understand language, including a Plain Language Summary of the results if the trial has been completed.

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2022
• Primary Completion (Actual): July 28, 2025
• Study Completion (Actual): July 28, 2025

Study Registration Dates

• First Submitted: January 7, 2022
• First Submitted That Met QC Criteria: February 1, 2022
• First Posted (Actual): February 2, 2022

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis
• Other Study ID Numbers: TAK-280-1501; 2023-504012-16-00 (Ctis: EU CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes