First-in-Human Trial of DS-2243a in Participants With Advanced Solid Tumors

NCT06644755 | Recruiting Phase 1 FDA Drug

• 1 other identifier: DS2243-054
• Study Type: interventional
• Target: 150
• Locations: 5 countries
• Sites: 7

Brief Summary

This 2-part study will evaluate safety, tolerability, and clinical efficacy of DS-2243a as a treatment for participants with advanced solid tumors.

Conditions

Solid Tumors; Sarcoma

Keywords

synovial sarcoma; ny-eso-1; DS-2243a; Myxoid Round cell Liposarcoma; sarcoma; NSCLC; UC; Bladder Cancer; NY-ESO; HLA-A2; Advanced solid tumors

Outcome Measures

Primary Outcomes (3)

• Part 1: Number of participants with Dose-Limiting Toxicities at each dose level of DS-2243a

  Up to 18 months

• Part 2: Number of participants with Treatment-Emergent Adverse Events

  Descriptive statistics of treatment-emergent adverse events (TEAEs)

  Up to 3 years

• Part 2: Objective Response Rate

  Objective Response Rate (ORR) as assessed by the investigator according to RECIST v1.1.

  From day of first dose up to 3 years

Secondary Outcomes (5)

• Part 1: Objective Response Rate

  From day of first dose up to 3 years

• Disease Control Rate

  From day of first dose up to 4 years.

• Progression-Free Survival (PFS)

  From day of first dose up to 4 years

• Overall Survival

  From day of first dose up to 4 years

• Drug Plasma Concentration

  Days 1, 2, and 3 during step-up dosing; Days 1, 2, 3, 5, 8, and 15 of Cycles 1 and 3; Day 1 of Cycle 2; and Day 1 of Cycle 4 and each subsequent cycle. A cycle may be up to 36 days.

Study Arms (5)

Part 1: Dose Escalation DS-2243a

EXPERIMENTAL

Participants will receive DS-2243a at escalating doses. The recommended dose for expansion (RDE) will be calculated using data collected from this population.

Drug: DS-2243a

Part 2: Dose Expansion SS/MRCLS

EXPERIMENTAL

Participants with synovial sarcoma or myxoid/round cell liposarcoma will receive DS-2243a at the recommended dose for expansion (RDE)

Drug: DS-2243a

Part 2: Dose Expansion Sq-NSCLC

EXPERIMENTAL

Participants with squamous cell carcinoma-non-small cell lung cancer will receive DS-2243a at the recommended dose for expansion (RDE)

Drug: DS-2243a

Part 2: Dose Expansion UC

EXPERIMENTAL

Participants with urothelial carcinoma will receive DS-2243a at the recommended dose for expansion (RDE)

Drug: DS-2243a

Part 2: Dose Expansion Ad-NSCLC

EXPERIMENTAL

Participants with adenocarcinoma-non-small cell lung cancer will receive DS-2243a at the recommended dose for expansion (RDE)

Drug: DS-2243a

Interventions

DS-2243a DRUG

Escalation Part: DS-2243a will be administered at escalating doses to determine the RDE Expansion Part: DS-2243a will be administered at RDE

Part 1: Dose Escalation DS-2243a; Part 2: Dose Expansion Ad-NSCLC; Part 2: Dose Expansion SS/MRCLS; Part 2: Dose Expansion Sq-NSCLC; Part 2: Dose Expansion UC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sign and date the main ICF.
• Adults ≥18 years at the time the biosample ICF or main ICF, whichever is signed first.
• Follow local regulatory requirements if the legal age of consent for trial participation is \>18 years old.
• One of the following histologically or cytologically documented cancers:
• Advanced (metastatic or unresectable) SS Advanced (metastatic or unresectable) MRCLS Metastatic or unresectable locally advanced NSCLC (Ad/Sq) Metastatic or unresectable locally advanced UC
• Relapsed from, refractory to, or intolerant to appropriate therapies \[eg, standard of care (SOC) therapy\] to provide clinical benefit for their condition as assessed by their physician and/or investigator. \[For South Korea only: Relapsed from, refractory to, or intolerant to all available therapies (eg, SOC therapy domestically approved) for their condition.\]
• HLA-A\*02:01, 02:02, 02:03, 02:04, 02:05, 02:06, 02:09, 02:10, or 02:11 positive.
• Has measurable disease based on RECIST v1.1 on computed tomography/magnetic resonance imaging (CT/MRI).
• Is willing and able to provide adequate pre-treatment or archival tumor tissue sample.
• Has Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1 at Screening.
• Meets the following required baseline local laboratory data within 14 days prior to start of trial intervention administration:
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × upper limit of normal (ULN) in participants with no liver metastasis, or ≤5 × ULN in participants with liver metastasis
• Total bilirubin (TBL) ≤1.5 × ULN (≤3 × ULN for participants with a documented history of Gilbert's syndrome)
• Absolute neutrophil count (ANC) ≥1.5 × 10\^9/L
• Platelet count ≥100 × 10\^9/L

You may not qualify if:

• Has received prior therapy targeting NY-ESO-1.
• Has an inadequate treatment washout period prior to the start of trial intervention, defined as follows:
• Radiation therapy: \<4 weeks (or \<2 weeks if palliative radiation therapy without abdominal/pelvic radiation)
• Chemotherapy, antibody-based anticancer therapy, immunotherapy: \<4 weeks
• Small molecules (eg, tyrosine kinase inhibitors): \<2 weeks or 5 half-lives, whichever is longer
• MRI/CT of the brain is required for all participants during Screening Period (see Section 8.3.1).
• Uncontrolled or clinically significant cardiovascular disease, including the following:
• Myocardial infarction within 6 months prior to screening
• Uncontrolled angina pectoris within 6 months prior to screening
• New York Heart Association (NYHA) Class III or IV congestive heart failure
• Left ventricular ejection fraction (LVEF) ≤50% or lower than the institutional lower limit of normal
• QT interval corrected with Fridericia's formula (QTcF) interval \>480 ms
• Chronic steroid treatment (IV or oral) or any other immunosuppressive medication (ie, prednisone \>10 mg daily (QD) or the equivalent).
• Has active other primary malignancies. Note: Participants with the following can be enrolled: Adequately resected non-melanoma skin cancer, curatively treated in situ disease, superficial cancer in the gastrointestinal tract curatively resected by endoscopic surgery, or any other solid tumors curatively treated with no evidence of recurrent disease for ≥3 years and requires no treatment.
• Has unresolved toxicities from previous anticancer treatment, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0, Grade ≤1 or baseline. Note: Participants with chronic, stable Grade 2 toxicities (defined as no worsening for 1 month prior to enrollment and managed with SOC treatment) that the investigator deems related to previous anticancer treatment may be enrolled. Such toxicities may include the following:

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (7)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

RECRUITING

UZ Leuven Europe Leuven

Leuven, 3000, Belgium

RECRUITING

Centre Leon Berard

Lyon, 6900, France

RECRUITING

Nederlands Kanker Instituut - Antoni van Leeuwenhoek Ziekenhuis (NKI-AVL)

Amsterdam, Netherlands

RECRUITING

Seoul National University Hospital

Seoul, South Korea

RECRUITING

MeSH Terms

Conditions

Sarcoma; Sarcoma, Synovial; Liposarcoma, Myxoid; Urinary Bladder Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Connective Tissue; Liposarcoma; Neoplasms, Adipose Tissue; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Central Study Contacts

Contact for Trial Information

CONTACT

908-992-6400; CTRinfo_us@daiichisankyo.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an open-label study.

Study Record Dates

• First Submitted: October 4, 2024
• First Posted: October 16, 2024
• Study Start: November 14, 2024
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): November 30, 2028
• Last Updated: July 24, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• 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.
• Access Criteria: 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.

Locations

FR (1); US (3); BE (1); KR (1); NL (1)