First-in-Human Study of TAK-280 in Participants With Unresectable Locally Advanced or Metastatic Cancer

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: Recruiting
• 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 (Estimated): 182
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Takeda Contact; Phone Number: +1-877-825-3327; Email: medinfoUS@takeda.com

Study Locations

• Australia
  • Bedford Park, Australia, 5042
    • Recruiting
    • Southern Oncology Clinical Research Unit
    • Contact: Site Contact; Phone Number: +61491679039; Email: ganessan.kichenadasse@socru.org.au
    • Principal Investigator: Ganessan Kichenadasse, MBBS, MD, FRACP
  • Clayton, Australia, 3168
    • Recruiting
    • Monash Medical Centre
    • Contact: Site Contact; Phone Number: 61736470372; Email: elizabeth.ahern@monashhealth.org
    • Principal Investigator: Elizabeth Ahern, Dr
  • Malvern, Australia, 3144
    • Recruiting
    • Cabrini Health
    • Contact: Site Contact; Phone Number: +61395096988; Email: gary.richardson@ocv.net.au
    • Principal Investigator: Gary Richardson, MD
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Recruiting
      • Chris O'Brien Lifehouse Hospital
      • Contact: Site Contact; Phone Number: +61 02 8514 0000; Email: Sarah.Sutherland@lh.org.au
      • Principal Investigator: Sarah Sutherland
• Canada
  • Quebec, Canada, G1J 1Z4
    • Recruiting
    • Centre Intégré de Cancérologie du CHU de Québec - Université Laval
    • Contact: Site Contact; Phone Number: (418) 525-4444; Email: olivier.dumas.med@ssss.gouv.qc.ca
    • Principal Investigator: Oliver Dumar
  • Sherbrooke, Canada, J1H 5N4
    • Recruiting
    • Centre Hospitalier Universitaire de Sherbrooke CHUS
    • Principal Investigator: Michel Pavic
    • Contact: Site Contact; Phone Number: 819 346 1110; Email: michel.pavic@usherbrooke.ca
• Spain
  • Barcelona, Spain, 08023
    • Recruiting
    • Hospital Quironsalud Barcelona, NEXT Oncology
    • Contact: Site Contact; Phone Number: +34932381661; Email: osaavedra@nextoncology.eu
    • Principal Investigator: Omar Saavedra
  • Barcelona, Spain, 08028
    • Recruiting
    • Hospital Universitari Dexeus - Grupo Quirónsalud
    • Principal Investigator: Maria Gonzalez Cao
    • Contact: Site Contact; Phone Number: +34935460135; Email: mgonzalezcao@oncorosell.com
  • Madrid, Spain, 28040
    • Recruiting
    • START MADRID_Hospital Universitario Fundacion Jimenez Diaz
    • Principal Investigator: Bernard Doger
    • Contact: Site Contact; Phone Number: 34915504800; Email: bernard.doger@startmadrid.com
  • Valencia, Spain, 46010
    • Recruiting
    • Hospital Clinico Universitario de Valencia
    • Contact: Site Contact; Phone Number: +34961973528; Email: vgambardella@incliva.es
    • Principal Investigator: Valentina Gambardella
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Recruiting
      • University of Arkansas for Medical Sciences
      • Contact: Site Contact; Phone Number: 501-686-8218; Email: mjbirrer@uams.edu
      • Principal Investigator: Micheal Birrer
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota - Masonic Cancer Center
      • Contact: Site Contact; Phone Number: 612-624-0937; Email: zorko004@umn.edu
      • Principal Investigator: Zorko Nicholas
  • Ohio
    • Cleveland, Ohio, United States, 44195-0001
      • Recruiting
      • The Cleveland Clinic Foundation
      • Contact: Site Contact; Phone Number: 216-444-1803; Email: maw4@ccf.org
      • Principal Investigator: Wen Ma
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Recruiting
      • Avera Cancer Institute
      • Principal Investigator: David Starks
      • Contact: Site Contact; Phone Number: 605-322-7535; Email: david.starks@avera.org
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • SCRI Tennessee Oncology Nashville
      • Contact: Site Contact; Phone Number: 615-329-7350; Email: benjamin.garmezy@sarahcannon.com
      • Principal Investigator: Benjamin Garmezy
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Froedtert and The Medical College of Wisconsin
      • Contact: Site Contact; Phone Number: 614-293-3885; Email: huchen@mcw.edu
      • Principal Investigator: Hui-Zi Chen

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 Treatment- emergent Adverse Events (TEAEs)		Up to approximately 37 months
Number of Participants With Dose Limiting Toxicities (DLTs)	DLT evaluation period is defined as the time between the initial dose of TAK-280 and Cycle 1 Day 28.	From start of the initial dose up to Cycle 1 Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of TAK-280	Cmax of TAK-280 will be reported.	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)
Area Under Plasma Concentration-Time Curve (AUC) of TAK- 280	AUC of TAK-280 will be reported.	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)
Time to Reach Maximum Observed Plasma Concentration (tmax) of TAK-280	tmax of TAK-280 will be reported.	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)
Terminal Disposition Phase Half-Life (t1/2) of TAK-280	t1/2 of TAK-280 will be reported.	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)
Total Clearance (CL) of TAK-280	CL of TAK-280 will be reported.	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)
Duration of Response (DOR) Based on RECIST V1.1	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).	Up to approximately 37 months
Progression Free Survival (PFS)	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.	From start of first dose to disease progression or death, whichever occurred first (up to approximately 37 months)
Overall Survival (OS)	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.	From start of first dose of study drug up to death (up to approximately 37 months)
Disease Control Rate	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.	Up to approximately 37 months
Percentage of Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) Having Prostate-Specific Antigen (PSA) Response	PSA response is defined as PSA reduction from baseline of >= 50 percent (%) and confirmed at least 3 weeks later.	Up to approximately 37 months
Duration of PSA Response in Participants With mCRPC	Duration of PSA response is defined as the time from first PSA response to first documented PSA progression.	Up to approximately 37 months
Time to PSA Progression in Participants With mCRPC	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.	Up to approximately 37 months
Percentage of Participants With mCRPC Having PSA Reductions of >= 50% up to 6 Months		Baseline up to 6 months
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)
Volume of Distribution at Steady State (Vss) After IV Administration of TAK-280	Vss of TAK-280 will be reported.	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)
Confirmed Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST V1.1)	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.	Up to approximately 37 months

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2022
• Primary Completion (Estimated): February 28, 2025
• Study Completion (Estimated): July 1, 2026

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): May 1, 2024
• Last Update Submitted That Met QC Criteria: April 30, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplastic Processes; Neoplasms; Neoplasm Metastasis; Neoplasms, Second Primary
• Other Study ID Numbers: TAK-280-1501; 2023-504012-16 (Other Identifier: 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