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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Takeda Development Center Americas Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

29 Apr 2024 → 29 Jul 2025

Decision date (initial)

2024-12-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Takeda Development Center Americas, Inc.

External identifiers

EU CT number

2023-504012-16-00

ClinicalTrials.gov

NCT05220098

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Safety, Pharmacogenomic, Pharmacokinetic, Dose response, Pharmacodynamic, Efficacy

To characterize the safety, tolerability, and DLTs of TAK-280 to determine the MTD (if any) and RP2D.

Secondary objectives 3

1. To characterize the PK of TAK-280.
2. To evaluate the preliminary antitumor activity of TAK-280 per Response Evaluation Criteria in Solid Tumors (RECIST) V1.1.
3. To characterize the potential immunogenicity of TAK-280.

Conditions and MedDRA coding

Unresectable Locally Advanced or Metastatic Cancer

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 01. Age greater than or equal to (>=)18 years or >= the local legal age of majority, as applicable.
2. 02. Criteria for disease state in dose escalation and cohort expansion. a. Tumor histologies during dose escalation: Dose escalation will begin by initially enrolling participants with histologically or pathologically confirmed, unresectable, locally advanced or metastatic cancers. b. Tumor histologies during cohort expansion: Participants will be eligible if they have histologically proven, unresectable, locally advanced or metastatic malignant neoplasms.
3. 03. Eastern Cooperative Oncology Group performance status (less than or equal to [<=]) 1.
4. 04. 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 8

1. 01. History of known autoimmune disease.
2. 02. Major surgery or traumatic injury within 8 weeks before the first dose of TAK-280.
3. 03. Unhealed wounds from surgery or injury.
4. 04. Ongoing or active infection of Grade >=2.
5. 05. Oxygen saturation less than (<) 92 percent (%) on room air at screening or during Cycle 1 Day 1 (C1D1) predose assessment.
6. 06. 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.
7. 07. 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.
8. 08. Known hypersensitivity to TAK-280 or any excipient.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 01. Number of Participants With Treatment- emergent Adverse Events (TEAEs) [Time Frame: Up to approximately 37 months]
2. 02. 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. [Time Frame: From start of the initial dose up to Cycle 1 Day 28]

Secondary endpoints 17

1. 01. Maximum Observed Plasma Concentration (Cmax) of TAK-280. Cmax of TAK-280 will be reported. [Time Frame: 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)]
2. 02. Area Under Plasma Concentration-Time Curve (AUC) of TAK- 280. AUC of TAK-280 will be reported. [Time Frame: 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)]
3. 03. Time to Reach Maximum Observed Plasma Concentration (tmax) of TAK-280. tmax of TAK-280 will be reported. [Time Frame: 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)]
4. 04. Terminal Disposition Phase Half-Life (t1/2) of TAK-280. t1/2 of TAK-280 will be reported. [Time Frame: 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)]
5. 05. Total Clearance (CL) of TAK-280. CL of TAK-280 will be reported. [Time Frame: 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)]
6. 06. Volume of Distribution at Steady State After Intravenous Administration (Vss) of TAK-280. Vss of TAK-280 will be reported. [Time Frame: 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)]
7. 07. 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. [Time Frame: Up to approximately 37 months]
8. 08. 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). [Time Frame: Up to approximately 37 months]
9. 09. 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. [Time Frame: From start of first dose to disease progression or death, whichever occurred first (up to approximately 37 months)]
10. 10. 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. [Time Frame: From start of first dose of study drug up to death (up to approximately 37 months)]
11. 11. 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. [Time Frame: Up to approximately 37 months]
12. 12. 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. [Time Frame: Up to approximately 37 months]
13. 13. 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. [Time Frame: Up to approximately 37 months]
14. 14. 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. [Time Frame: Up to approximately 37 months]
15. 15. Percentage of Participants With mCRPC Having PSA Reductions of >= 50% up to 6 Months [Time Frame: Baseline up to 6 months]
16. 16. 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)]
17. 17. Percentage of Participants who Developed Neutralizing Antibody (NAb) Titers for TAK-280 [Time Frame: Cycle 1 to 5: pre-dose (Each cycle= 28 days)]

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Takeda Development Center Americas Inc.

Sponsor organisation

Takeda Development Center Americas Inc.

Address

95 Hayden Avenue

City

Lexington

Postcode

02421-7942

Country

United States

Scientific contact point

Organisation

Takeda Development Center Americas Inc.

Contact name

Xin Ma

Public contact point

Organisation

Takeda Development Center Americas Inc.

Contact name

Takeda

Third parties 22

Locations

2 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 26 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications