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

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.

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.

Dose-escalation Phase is non-randomized and Cohort-expansion Phase will include randomized and non-randomized cohorts.

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.

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.

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)

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)

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)

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)

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)

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)

Percentage of Participants With 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.

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).

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)

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.

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.

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.

Duration of PSA response is defined as the time from first PSA response to first documented PSA progression.

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.

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. Tumor histologies during dose escalation: Dose escalation will begin by initially enrolling participants with histologically or pathologically confirmed, unresectable, locally advanced or metastatic cancers. 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 PC and only bone metastases (these participants are allowed in the study). 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. Inactivated annual influenza vaccination is allowed. Known hypersensitivity to TAK-280 or any excipient.

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 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.