First-in-Human Study of TAK-280 in Participants With Unresectable Locally Advanced or Metastatic Cancer
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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. |
Drug: TAK-280
Participants will receive TAK-280 as IV infusion.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Treatment- emergent Adverse Events (TEAEs) [Up to approximately 37 months]
- Recommended Phase 2 Dose (RP2D) of TAK-280 [Up to approximately 37 months]
The RP2D is the maximum tolerated dose (MTD) or less.
- Number of Participants With Dose Limiting Toxicities (DLTs) [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 [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 Outcome 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) [Up to approximately 37 months]
- Duration of Response (DOR) Based on mRECIST 1.1 [Up to approximately 37 months]
- Progression Free Survival (PFS) [From start of first dose to disease progression or death, whichever occurred first (up to approximately 37 months)]
- Overall Survival (OS) [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 [Baseline up to 6 months]
- Maximum Observed Plasma Concentration (Cmax) of TAK-280 [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 [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 [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 [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 [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 [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 [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 [Cycle 1 to 5: pre-dose (Each cycle= 28 days)]
Percentage of participants who develop positive induced ADA for TAK-280 will be reported.
Eligibility Criteria
Criteria
Inclusion Criteria
-
Age greater than or equal to (>=)18 years.
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Criteria for disease state.
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Dose-escalation tumor histologies: Dose escalation will begin by initially enrolling participants with histologically or pathologically confirmed, unresectable, locally advanced or metastatic cancers.
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Cohort-expansion tumor histologies: Participants will be eligible if they have histologically proven, unresectable, locally advanced or metastatic malignant neoplasms.
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Eastern Cooperative Oncology Group performance status (less than or equal to [<=]) 1.
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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
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History of known autoimmune disease.
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Major surgery or traumatic injury within 8 weeks before the first dose of TAK-280.
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Unhealed wounds from surgery or injury.
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Ongoing or active infection of Grade >=2.
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Oxygen saturation < 92% on room air at screening or during C1D1 predose assessment.
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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.
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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.
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Known hypersensitivity to TAK-280 or any excipient.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Monash Medical Centre | Clayton | Australia | 3168 |
Sponsors and Collaborators
- Takeda
- Takeda Development Center Americas, Inc.
Investigators
- Study Director: Study Director, Takeda
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- TAK-280-1501