First-in-Human Study of DS-3939a in Participants With Advanced Solid Tumors

Phase 1/2, Open-label, Multicenter, First-in-Human Study of DS-3939a in Subjects With Advanced Solid Tumors

This study will evaluate the safety, tolerability, and efficacy of DS-3939a in participants with advanced solid tumors.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor; Metastatic Solid Tumor
• Intervention / Treatment: Drug: DS-3939a

Detailed Description

DS-3939a is an antibody drug conjugate (ADC) being developed for the treatment of malignant tumors. This is a first-in-human, dose-escalating clinical study divided into 2 parts: the Dose Escalation Part (Part 1) and the Dose Expansion Part (Part 2).

• Study Type: Interventional
• Enrollment (Estimated): 430
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: (US sites) Daiichi Sankyo Contact for Clinical Trial Information; Phone Number: 908-992-6400; Email: CTRinfo@dsi.com
• Study Contact Backup: Name: (Asia Sites) Daiichi Sankyo Contact for Clinical Trial Information; Phone Number: +81-3-6225-1111 (M-F 9-5 JST); Email: dsclinicaltrial@daiichisankyo.co.jp

Study Locations

• Japan
  • Chiba, Japan, 277-8577
    • Recruiting
    • National Cancer Center Hospital East
    • Contact: See Central Contact
  • Tokyo, Japan, 104-0045
    • Recruiting
    • National Cancer Center Hospital
    • Contact: See Central Contact
• United States
  • Florida
    • Sarasota, Florida, United States, 34232
      • Recruiting
      • Florida Cancer Specialists
      • Contact: Principal Investigator
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Recruiting
      • Rhode Island Hospital
      • Contact: Principal Investigator
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • Huntsman Cancer Institute, University of Utah
      • Contact: Principal Investigator

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Sign and date the main Informed Consent Form (ICF).
• Has a left ventricular ejection fraction ≥50% by either an echocardiogram or multigated acquisition within 28 days of enrollment.
• Has adequate organ function.
• Measurable disease based on RECIST V1.1.
• Eastern Cooperative Oncology Group performance status score of 0 or 1.

Additional inclusion criteria for Part 1

• Has a histologically or cytologically documented locally advanced, metastatic, or unresectable urothelial, non-small cell lung, breast, ovarian, or biliary tract cancers, or pancreatic ductal adenocarcinoma, regardless of any molecular subtypes.

Additional inclusion criteria for Part 2

• Has a histologically or cytologically documented locally advanced, metastatic, or unresectable cancer meeting the protocol criteria and documented radiographic disease progression during or after the most recent anticancer therapy.

• Is able to provide either of the following baseline tumor samples:

  • Fresh core needle biopsy samples obtained during the Screening Period, or
  • Alternative FFPE tumor tissue samples obtained by biopsy or surgery performed after the completion date of the most recent anticancer therapy regimen and within 6 months before signing the ICF

Exclusion Criteria:

• Has had prior treatment targeting mucin 1 (MUC1) or TA-MUC1.
• Has spinal cord compression or history of/clinically active central nervous system metastases.
• Has multiple primary malignancies, except adequately resected nonmelanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated, with no evidence of disease for ≥3 years.
• Has a history of noninfectious interstitial lung disease (ILD)/pneumonitis (including suspected one), has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
• Has active human immunodeficiency virus (HIV) infection as determined by plasma HIV ribonucleic acid viral load and cluster of differentiation 4 count.
• Has evidence of active hepatitis B virus or hepatitis C virus infection.
• Any of the following within the past 6 months: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event.
• Has an active, known, or suspected autoimmune disease.
• Current participation in other therapeutic investigational procedures, except for participation in Long Term Follow-Up without any investigational treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation (Part 1); Participants with locally advanced, metastatic, or unresectable tumors who will receive an intravenous (IV) infusion of DS-3939a.	Drug: DS-3939a; One IV infusion Q3W on Day 1 of each 21-day cycle
Experimental: Dose Expansion (Part 2); Multiple expansion cohorts targeting various advanced solid tumors.	Drug: DS-3939a; One IV infusion Q3W on Day 1 of each 21-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Dose-limiting Toxicities Following Treatment With DS-3939a	Approximately 3 months after first dosing
Overall Number of Participants with Treatment-emergent Adverse Events and Serious Adverse Events Following Treatment With DS-3939a	Up to approximately 31 months
Number of Participants with Objective Response Rate Following Treatment With DS-3939a (Part 2)	Up to approximately 31 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Objective Response Rate Following Treatment With DS-3939a (Part 1)	Up to approximately 31 months
Disease Control Rate Following Treatment With DS-3939a	Up to approximately 31 months
Duration of Response Following Treatment With DS-3939a	Up to approximately 31 months
Time to Response Following Treatment With DS-3939a	Up to approximately 31 months
Progression Free Survival Following Treatment With DS-3939a	Up to approximately 31 months
Overall Survival Following Treatment With DS-3939a	Up to approximately 31 months
TA-MUC1 Expression by Immunohistochemistry Following Treatment With DS-3939a	At Cycle 1 Day 1
Area Under the Plasma Concentration Curve (AUC) Following Treatment With DS-3939a	Cycles 1 & 3: Days 1, 2, 4, 8 & 15; Cycle 2: Day 1 & 1 time between Days 3 to 8 (Part 2 Only); Cycles 4 & every 2 cycles thereafter up to 31 months: Day 1 (each cycle is 21 days)
Maximum Plasma Concentration (Cmax) Following Treatment With DS-3939a	Cycles 1 & 3: Days 1, 2, 4, 8 & 15; Cycle 2: Day 1 & 1 time between Days 3 to 8 (Part 2 Only); Cycles 4 & every 2 cycles thereafter up to 31 months: Day 1 (each cycle is 21 days)
Time to Maximum Plasma Concentration (Tmax) Following Treatment With DS-3939a	Cycles 1 & 3: Days 1, 2, 4, 8 & 15; Cycle 2: Day 1 & 1 time between Days 3 to 8 (Part 2 Only); Cycles 4 & every 2 cycles thereafter up to 31 months: Day 1 (each cycle is 21 days)
Minimum Observed Concentration (Ctrough) Following Treatment With DS-3939a	Cycles 1 & 3: Days 1, 2, 4, 8 & 15; Cycle 2: Day 1 & 1 time between Days 3 to 8 (Part 2 Only); Cycles 4 & every 2 cycles thereafter up to 31 months: Day 1 (each cycle is 21 days)
Terminal Half-Life (T1/2) Following Treatment With DS-3939a	Cycles 1 & 3: Days 1, 2, 4, 8 & 15; Cycle 2: Day 1 & 1 time between Days 3 to 8 (Part 2 Only); Cycles 4 & every 2 cycles thereafter up to 31 months: Day 1 (each cycle is 21 days)
Number of Participants With Treatment-emergent Anti-drug Antibodies Following Treatment With DS-3939a	Up to approximately 47 months

Collaborators and Investigators

• Sponsor: Daiichi Sankyo
• Investigators: Study Director: Global Clinical Leader, Daiichi Sankyo

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2023
• Primary Completion (Estimated): March 17, 2026
• Study Completion (Estimated): July 11, 2027

Study Registration Dates

• First Submitted: May 10, 2023
• First Submitted That Met QC Criteria: May 12, 2023
• First Posted (Actual): May 25, 2023

Study Record Updates

• Last Update Posted (Actual): May 10, 2024
• Last Update Submitted That Met QC Criteria: May 9, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: advanced/metastatic solid tumors; DS-3939a; anti-body drug conjugate
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: DS3939-077

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