First-in-Human Trial of DS1025a in Participants With Advanced Solid Tumors

A Phase 1, Multicenter, Open-label, First-in-Human Trial of DS1025a in Participants With Advanced Solid Tumors

This clinical trial is designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy signals of DS1025a, given as a single agent to participants with advanced, metastatic, or unresectable solid tumors.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Solid Tumor; Metastatic Solid Tumor; Unresectable Solid Tumor
• Intervention / Treatment: Drug: DS1025a

Detailed Description

This is a global, multicenter, open-label, FIH, dose escalation trial for participants with advanced, metastatic, or unresectable solid tumors. The primary objectives of the trial are to evaluate the safety and tolerability of DS1025a in solid tumors participants and to determine the recommended dose for expansion (RDE). RDE determination will be based on the totality of the data, including safety, efficacy, PK/PD, and biomarkers. The primary endpoints of the trial are DLTs, AEs, and DS1025a discontinuation due to AEs. Secondary and exploratory objectives are to evaluate efficacy, PK, and PD of DS1025a.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Daiichi Sankyo Contact for Clinical Trial Information; Phone Number: 908-992-6400; Email: CTRinfo_us@daiichisankyo.com

Study Locations

• Japan
  • Chiba, Japan, 277-8577
    • National Cancer Center Hospital East
    • Contact: Principal Investigator
  • Osaka, Japan, 573-1191
    • Kansai Medical University Hospital
    • Contact: Principal Investigator
  • Tokyo, Japan, 135-8550
    • The Cancer Institute Hospital Of JFCR
    • Contact: Principal Investigator

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

To be eligible to participate in this trial, an individual must meet all the following criteria:

1. Sign and date the main ICF, prior to the start of any trial-specific procedures.
2. Adults ≥18 years of age at the time the ICF is signed (Please follow local regulatory requirements if the legal age of consent for trial participation is >18 years old).
3. Histologically documented, advanced, metastatic, or unresectable solid tumors.
4. Relapsed or refractory disease, following at least 1 line of therapy, not amenable to standard therapy.
5. Is willing to provide a newly obtained tumor tissue sample at screening, if not clinically contraindicated and at an acceptable risk as determined by the Investigator. If a fresh tumor biopsy is not clinically feasible or would pose unacceptable risk, an archival tumor tissue sample (obtained within 24 months of consent) must be submitted.
6. Has measurable disease based on local CT/MRI imaging as assessment by the Investigator using RECIST v1.1; radiographic tumor assessment must be performed within 28 days prior to initiation of trial intervention.
7. ECOG PS of 0 or 1 assessed no more than 28 days prior to initiation of trial intervention.
8. Has adequate organ and bone marrow function as assessed by local laboratory within 14 days prior to initiation of trial intervention as defined in the protocol.

9. A WOCBP is eligible to participate if the following conditions are met:

   • Participant is not pregnant as confirmed by highly sensitive pregnancy test
   • Participant does not plan to breastfeed during the Trial Intervention Period and for at least 8 months after last dose of trial intervention.
   • Participant agrees to adhere to a contraceptive method that is highly effective with low user dependency only and agrees not to donate eggs (ova, oocytes) to others or freeze/store eggs during the Treatment Period and for at least the time needed to eliminate the trial intervention after the last dose.

10. A male participant capable of producing sperm is eligible to participate if he agrees to the following during the intervention period and for at least the time needed to eliminate the trial intervention:

    • Avoid donating sperm.
    • Adhere to approved contraception method as specified in the protocol.

An individual who meets any of the following criteria will be excluded from participation in this trial:

1. Prior treatment with an anti-CD25 therapy.
2. Treatment discontinuation history due to toxicity to a DXd-ADC agent and considered not able to tolerate DS1025a based on the discussion between the investigator and the Sponsor (for participants who have DXd-ADC treatment history).
3. Inadequate washout period before initiation of trial intervention as specified in the protocol.
4. Has spinal cord compression or clinically active central nervous system tumors, including metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
5. Uncontrolled or significant cardiovascular disease as specified in the protocol.
6. Any of the following within the past 6 months prior to initiation of trial intervention: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event.
7. Participants with any history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use, or current ILD, or suspected ILD, or ILD that cannot be ruled out by imaging at screening.
8. Lung-specific intercurrent clinically significant illnesses as specified in the protocol.
9. Has clinically significant pulmonary compromise or requirement for supplemental oxygen.
10. History of other active malignancy within 3 years prior to initiation of trial intervention, with the exception of those with a negligible risk of metastasis or death (eg, 5-year OS rate >90%) and treated with expected curative outcome
11. Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE v 6.0, Grade ≤1 or baseline.
12. History of hypersensitivity to any excipients in DS1025a or any known contraindication to treatment with, including hypersensitivity to, the trial intervention.
13. Has a known history of HLH.
14. Has a known active infection, or reactivation of latent following infections as specified in the protocol among participants who received treatment such as antivirals, antifungals, or IV antibiotics within 14 days prior to first dose of trial intervention.
15. Has active or uncontrolled HBV infection.
16. Has active or uncontrolled HCV infection.
17. Has active or uncontrolled HIV infection.
18. Has an active, known, or suspected autoimmune disease.
19. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (>10 mg daily prednisone equivalents) or any other form of immunosuppressive therapy within 14 days prior to the trial intervention.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation: DS1025a; Participants with advanced, metastatic, or unresectable solid tumors will receive DS1025a on Day 1.	Drug: DS1025a; Administered on Day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Reporting Dose-limiting Toxicities (DLTs)	Day 1 up to approximately 12 months
Number of Participants Reporting Adverse Events (AEs)	Screening up to long-term survival follow up every 12 weeks, up to approximately 12 months
Number of Participants Reporting Discontinuation of DS1025a Due to AEs	Screening up to long-term survival follow up every 12 weeks, up to approximately 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Parameter Area Under the Plasma-Concentration Curve (AUC)	Area under the curve over the dosing interval (AUCtau) and Area under the plasma concentration-time curve up to the last quantifiable time (AUClast) will be assessed.	Predose up to approximately 12 months
Pharmacokinetic Parameter Maximum Concentration (Cmax)		Predose up to approximately 12 months
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax)		Predose up to approximately 12 months
Pharmcokinetic Parameter Concentration at Trough Level (Ctrough)		Predose up to approximately 12 months
Percentage of Participants Who Are ADA Positive and Percentage of Participants Who Have Treatment-emergent ADAs		Day 1 up to approximately 12 months

Collaborators and Investigators

• Sponsor: Daiichi Sankyo

Study record dates

Study Major Dates

• Study Start (Estimated): August 3, 2026
• Primary Completion (Estimated): January 21, 2028
• Study Completion (Estimated): January 21, 2029

Study Registration Dates

• First Submitted: June 26, 2026
• First Submitted That Met QC Criteria: June 26, 2026
• First Posted (Actual): July 2, 2026

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: June 26, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Advanced Solid Tumor; Metastatic Solid Tumor; Unresectable Solid Tumor; DS1025a
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis
• Other Study ID Numbers: DS1025-103; 2026-525284-41-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No