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

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.

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.