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

Overview

The main aim of this study is to find out the safety and tolerability of TAK- 280 in participants with unresectable, locally advanced or metastatic cancer failing or intolerant to standard therapies. The study consists of a dose-escalation phase to determine the recommended dose of TAK-280 for the cohort-expansion phase. Cohort-expansion phase will further define the safety and initial efficacy of TAK-280. Participants will be treated with TAK-280 for up to 14 treatment cycles for a maximum total of 56 doses of TAK-280. Each treatment cycle will be 28 days. Participants will be treated with TAK- 280 until disease progression, unacceptable toxicity, or withdrawal from study occurs. Their cancer will be treated by their doctor according to their doctor's usual clinical practice. After the last dose of study drug, participants will be followed up for survival every 12 weeks for at least 52 weeks.

Full Title of Study: “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

• Study Type: Interventional
• Study Design
  • Allocation: N/A
  • Intervention Model: Sequential Assignment
  • Primary Purpose: Treatment
  • Masking: None (Open Label)
• Study Primary Completion Date: February 28, 2025

Detailed Description

This study consists of 2 phases: Dose-escalation and cohort-expansion phase. Dose-escalation phase: Dose escalation will be conducted in participants with histologically proven, unresectable, locally advanced or metastatic cancers and the Bayesian Optimal Interval (BOIN) design will be used. Cohort-Expansion Phase: During the cohort-expansion phase, 5 separate participant cohorts will be enrolled, based on the tumor type. The dosing regimen used in the expansion cohorts will be the recommended phase 2 dose (RP2D) and schedule based on the safety, pharmacokinetics (PK), and antitumor activity findings from the dose-escalation phase of the study. Enrollment into the expansion cohorts is based on a Simon 2-stage design.

Interventions

• Drug: TAK-280
  • Participants will receive TAK-280 as IV infusion.

Arms, Groups and Cohorts

• Experimental: TAK-280
  • Participants will receive TAK-280 for up to 14 treatment cycles (Each treatment Cycle = 28 days) until disease progression, unacceptable toxicity, or withdrawal from study occurs.

Clinical Trial Outcome Measures

Primary Measures

• Number of Participants With Treatment- emergent Adverse Events (TEAEs)
  • Time Frame: Up to approximately 37 months
• Recommended Phase 2 Dose (RP2D) of TAK-280
  • Time Frame: Up to approximately 37 months
  • The RP2D is the maximum tolerated dose (MTD) or less.
• Number of Participants With Dose Limiting Toxicities (DLTs)
  • Time Frame: From start of the initial dose up to Cycle 1 Day 28
  • DLT evaluation period is defined as the time between the initial dose of TAK-280 and Cycle 1 Day 28.
• Maximum Tolerated Dose (MTD) of TAK-280
  • Time Frame: Up to approximately 37 months
  • MTD is selected as the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate of 30%.

Secondary Measures

• Percentage of Participants With Confirmed Overall Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (mRECIST 1.1)
  • Time Frame: Up to approximately 37 months
• Duration of Response (DOR) Based on mRECIST 1.1
  • Time Frame: Up to approximately 37 months
• Progression Free Survival (PFS)
  • Time Frame: From start of first dose to disease progression or death, whichever occurred first (up to approximately 37 months)
• Overall Survival (OS)
  • Time Frame: From start of first dose of study drug up to death (up to approximately 37 months)
• Percentage of Participants With Prostrate Cancer (PC) Having Prostate-Specific Antigen (PSA) Reduction of >= 50% up to 6 Months
  • Time Frame: Baseline up to 6 months
• Maximum Observed Plasma Concentration (Cmax) of TAK-280
  • Time Frame: Cycle 1 Day 1: 0 (Pre-dose) to 48 hours, Day 8, 15: 0 to 6 hours, Day 22: 0 to 1 hour; Cycle 2 Day 1, 8, 15, 22: 0 to 1 hour; Cycle 3 Day 1: 0 to 4 hours; Day 8, 15, 22: 0 to 1 hour; Cycle 5 Day 1: 0 to 1 hour post-dose (Each cycle = 28 days)
  • Cmax of TAK-280 will be reported.
• Area Under Plasma Concentration-Time Curve (AUC) of TAK- 280
  • Time Frame: Cycle 1 Day 1: 0 (Pre-dose) to 48 hours, Day 8, 15: 0 to 6 hours, Day 22: 0 to 1 hour; Cycle 2 Day 1, 8, 15, 22: 0 to 1 hour; Cycle 3 Day 1: 0 to 4 hours; Day 8, 15, 22: 0 to 1 hour; Cycle 5 Day 1: 0 to 1 hour post-dose (Each cycle = 28 days)
  • AUC of TAK-280 will be reported.
• Time to Reach Maximum Observed Plasma Concentration (tmax) of TAK-280
  • Time Frame: Cycle 1 Day 1: 0 (Pre-dose) to 48 hours, Day 8, 15: 0 to 6 hours, Day 22: 0 to 1 hour; Cycle 2 Day 1, 8, 15, 22: 0 to 1 hour; Cycle 3 Day 1: 0 to 4 hours; Day 8, 15, 22: 0 to 1 hour; Cycle 5 Day 1: 0 to 1 hour post-dose (Each cycle = 28 days)
  • tmax of TAK-280 will be reported.
• Terminal Disposition Phase Half-Life (t1/2) of TAK-280
  • Time Frame: Cycle 1 Day 1: 0 (Pre-dose) to 48 hours, Day 8, 15: 0 to 6 hours, Day 22: 0 to 1 hour; Cycle 2 Day 1, 8, 15, 22: 0 to 1 hour; Cycle 3 Day 1: 0 to 4 hours; Day 8, 15, 22: 0 to 1 hour; Cycle 5 Day 1: 0 to 1 hour post-dose (Each cycle = 28 days)
  • t1/2 of TAK-280 will be reported.
• Total Clearance (CL) of TAK-280
  • Time Frame: Cycle 1 Day 1: 0 (Pre-dose) to 48 hours, Day 8, 15: 0 to 6 hours, Day 22: 0 to 1 hour; Cycle 2 Day 1, 8, 15, 22: 0 to 1 hour; Cycle 3 Day 1: 0 to 4 hours; Day 8, 15, 22: 0 to 1 hour; Cycle 5 Day 1: 0 to 1 hour post-dose (Each cycle = 28 days)
  • CL of TAK-280 will be reported.
• Volume of Distribution at Steady State After Intravenous Administration (Vss) of TAK-280
  • Time Frame: Cycle 1 Day 1: 0 (Pre-dose) to 48 hours, Day 8, 15: 0 to 6 hours, Day 22: 0 to 1 hour; Cycle 2 Day 1, 8, 15, 22: 0 to 1 hour; Cycle 3 Day 1: 0 to 4 hours; Day 8, 15, 22: 0 to 1 hour; Cycle 5 Day 1: 0 to 1 hour post-dose (Each cycle = 28 days)
  • VSS of TAK-280 will be reported.
• Percentage of Participants who Develop Cytokines for TAK-280
  • Time Frame: Cycle 1 to 5: pre-dose (Each cycle= 28 days)
  • Percentage of participants who develop cytokines for TAK-280 will be reported.
• Percentage of Participants who Develop Positive Induced Antidrug Antibody (ADA) for TAK-280
  • Time Frame: Cycle 1 to 5: pre-dose (Each cycle= 28 days)
  • Percentage of participants who develop positive induced ADA for TAK-280 will be reported.

Participating in This Clinical Trial

Inclusion Criteria

• Age greater than or equal to (>=)18 years. – Criteria for disease state. 1. Dose-escalation tumor histologies: Dose escalation will begin by initially enrolling participants with histologically or pathologically confirmed, unresectable, locally advanced or metastatic cancers. 2. Cohort-expansion tumor histologies: 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 modified Response Evaluation Criteria in Solid Tumors (mRECIST) Version 1.1 and documented by CT and/or MRI except for participants with PC with only bone metastases. 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 < 92% on room air at screening or during C1D1 predose assessment. – Inflammatory process that has not resolved >= 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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Takeda
• Collaborator
  • Takeda Development Center Americas, Inc.
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Official(s)
  • Study Director, Study Director, Takeda
• Overall Contact(s)
  • Takeda Contact, +1-877-825-3327, medinfoUS@takeda.com