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

Phase 2TerminatedNCT05220098

Takeda69 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Unresectable Locally Advanced or Metastatic Cancer

Interventions

TAK-280DRUG

Participants will receive TAK-280 as IV infusion.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (23)

University of Arkansas For Medical Sciences

Little Rock, Arkansas, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: From start of study drug administration up to follow-up (up to 37 weeks)

Secondary Outcomes

Maximum Observed Plasma Concentration (Cmax) of TAK-280

Cmax for TAK-280 was reported.

Time frame: 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.

Time frame: 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.

Time frame: 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)

Data from ClinicalTrials.gov

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University of California San Francisco

San Francisco, California, United States

University of Minnesota - Masonic Cancer Center

Minneapolis, Minnesota, United States

Duke Cancer Institute

Durham, North Carolina, 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

...and 13 more locations

Time to Reach Maximum Observed Plasma Concentration (Tmax) of TAK-280

Tmax for TAK-280 was reported.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Up to 37 weeks