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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 1/2, First-in-Human, Open-Label, Dose-Escalation Study of TAK-280 in Patients With Unresectable Locally Advanced or Metastatic Cancer

Conditions
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Unresectable Locally Advanced or Metastatic Cancer

Intervention / Treatment
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* Drug: TAK-280


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Dose-escalation Phase is non-randomized and Cohort-expansion Phase will include randomized and non-randomized cohorts.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose-escalation Phase: TAK-280<br>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<br>* Participants will receive TAK-280 as IV infusion.<br>|
| Experimental: Cohort-expansion Phase: TAK-280 High or low Dose<br>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<br>* Participants will receive TAK-280 as IV infusion.<br>|

What is the study measuring?
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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) | 
| Volume of Distribution at Steady State After Intravenous Administration (Vss) 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) | 
| 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. | Up to approximately 37 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) |