Clinical trial NCT05220098: First-in-Human Study of TAK-280 in Participants With Solid Tumors
Official title: A Phase 1/2, First-in-Human, Open-Label, Dose-Escalation Study of TAK-280 in Patients With Unresectable Locally Advanced or Metastatic Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Unresectable Locally Advanced or Metastatic Cancer
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Takeda Development Center Americas, Inc.
First posted: 2022-02-02
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose-escalation Phase is non-randomized and Cohort-expansion Phase will include randomized and non-randomized cohorts.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: From start of the initial dose up to Cycle 1 Day 28
measure: Number of Participants With Treatment- emergent Adverse Events (TEAEs)
timeFrame: Up to approximately 37 months
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of TAK-280
timeFrame: 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)
measure: Area Under Plasma Concentration-Time Curve (AUC) of TAK- 280
timeFrame: 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)
measure: Time to Reach Maximum Observed Plasma Concentration (tmax) of TAK-280
timeFrame: 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)
measure: Terminal Disposition Phase Half-Life (t1/2) of TAK-280
timeFrame: 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)
measure: Total Clearance (CL) of TAK-280
timeFrame: 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)
measure: Volume of Distribution at Steady State (Vss) After IV Administration of TAK-280
timeFrame: 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)
measure: Confirmed Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST V1.1)
timeFrame: Up to approximately 37 months
measure: Duration of Response (DOR) Based on RECIST V1.1
timeFrame: Up to approximately 37 months
measure: Progression Free Survival (PFS)
timeFrame: From start of first dose to disease progression or death, whichever occurred first (up to approximately 37 months)
measure: Overall Survival (OS)
timeFrame: From start of first dose of study drug up to death (up to approximately 37 months)
measure: Disease Control Rate
timeFrame: Up to approximately 37 months
measure: Percentage of Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) Having Prostate-Specific Antigen (PSA) Response
timeFrame: Up to approximately 37 months
measure: Duration of PSA Response in Participants With mCRPC
timeFrame: Up to approximately 37 months
measure: Time to PSA Progression in Participants With mCRPC
timeFrame: Up to approximately 37 months
measure: Percentage of Participants With mCRPC Having PSA Reductions of >= 50% up to 6 Months
timeFrame: Baseline up to 6 months
measure: Percentage of Participants who Develop Positive Induced Antidrug Antibody (ADA) for TAK-280
timeFrame: Cycle 1 to 5: pre-dose (Each cycle= 28 days)
measure: Percentage of Participants who Developed Neutralizing Antibody (NAb) Titers for TAK-280
timeFrame: Cycle 1 to 5: pre-dose (Each cycle= 28 days)
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas For Medical Sciences
state: Arkansas
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Minneapolis
country: United States
facility: University of Minnesota - Masonic Cancer Center
state: Minnesota
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Sioux Falls
country: United States
facility: Sanford Cancer Center
state: South Dakota
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Nashville
country: United States
facility: SCRI Tennessee Oncology Nashville
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Froedtert and The Medical College of Wisconsin
state: Wisconsin
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse Hospital
state: New South Wales
city: Bedford Park
country: Australia
facility: Southern Oncology Clinical Research Unit
city: Clayton
country: Australia
facility: Monash Medical Centre
city: Malvern
country: Australia
facility: Cabrini Health
city: Quebec
country: Canada
facility: Centre Intégré de Cancérologie du CHU de Québec - Université Laval
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke CHUS
city: Barcelona
country: Spain
facility: Hospital Quironsalud Barcelona, NEXT Oncology
city: Barcelona
country: Spain
facility: Hospital Universitari Dexeus - Grupo Quironsalud
city: Barcelona
country: Spain
facility: Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON
city: Madrid
country: Spain
facility: START MADRID_Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: