A Study of DS-1103a Combination Therapy in Participants With Advanced Solid Tumors

NCT05765851 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: DS1103-0742023-503965-48-00
• Study Type: interventional
• Target: 108
• Locations: 4 countries
• Sites: 8

Brief Summary

This study will evaluate the safety and efficacy of DS-1103a combination therapy in participants with advanced solid tumors.

Conditions

Advanced Solid Tumor

Keywords

Advanced Solid Tumor; DS-1103a; CD47; SIRPa

Outcome Measures

Primary Outcomes (4)

• Number of Participants with Dose-limiting Toxicities (Dose Escalation)

  From Cycle 1 Day 1 to Cycle 2 Day 21 (each cycle is 21 days)

• Number of Participants with Dose-limiting Toxicities Following DS-1103a Combination Therapy (Dose Expansion; Cohort 2)

  From Cycle 1 Day 1 to Cycle 1 Day 21 (each cycle is 21 days)

• Overall Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events (Dose Escalation and Dose Expansion)

  Screening through long-term follow up, up to approximately 91 months

• Objective Response Rate Assessed by Blinded Independent Central Review Following DS-1103a Combination Therapy (Dose Expansion)

  Objective response rate (ORR) is defined as the proportion of participants with a best overall response of confirmed complete response (CR) or confirmed partial response (PR) as assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria In Solid Tumors v1.1.

  Baseline (Dose Expansion) up until documented progressive disease, unacceptable toxicity, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years 11 months

Secondary Outcomes (9)

• Objective Response Rate Assessed by Investigator (Dose Escalation and Dose Expansion)

  Baseline up until documented progressive disease, unacceptable toxicity, death, lost to follow-up, or withdrawal by the participant, up to approximately 91 months

• Disease Control Rate Assessed by Investigator (Dose Escalation and Dose Expansion) and Blinded Independent Central Review (Dose Expansion)

  Baseline up until documented progressive disease, unacceptable toxicity, death, lost to follow-up, or withdrawal by the participant, up to approximately 91 months

• Clinical Benefit Rate Assessed by Investigator (Dose Escalation and Dose Expansion) and Blinded Independent Central Review (Dose Expansion)

  Baseline up until documented progressive disease, unacceptable toxicity, death, lost to follow-up, or withdrawal by the participant, up to approximately 91 months

• Duration of Response Assessed by Investigator (Dose Escalation and Dose Expansion) and Blinded Independent Central Review (Dose Expansion)

  Baseline up until documented progressive disease, unacceptable toxicity, death, lost to follow-up, or withdrawal by the participant, up to approximately 91 months

• Pharmacokinetic Parameter Area Under the Plasma Concentration Curve for DS-1103a (Dose Escalation and Dose Expansion)

  Dose Escalation: Cycles 1,2, and 4: Days 1,2,4,8,15; Cycle 3 Days 1,8,15; Cycle 6 and 8 Day 1; Dose Expansion: Cycles 1 and 3: Days 1,2,4,8,15; Cycle 2 Days 1,8,15; Cycle 4,6, and 8 Day 1 (each cycle is 21 days)

Study Arms (3)

Dose Escalation: DS-1103a + T-DXd

EXPERIMENTAL

Participants with HER2-expressing or HER2-mutated advanced metastatic solid tumors who will receive an escalating intravenous (IV) infusion of DS-1103a (starting dose of 100 mg) every 3 weeks (Q3W) starting on Cycle 1 Day 1. Starting on Cycle 2 Day 1 and on Day 1 of each subsequent cycle, participants will also receive T-DXd IV Q3W.

Drug: DS-1103a; Drug: T-DXd

Dose Expansion (Cohort 1): DS-1103a + T-DXd

EXPERIMENTAL

Participants with a specific HER2-altered advanced solid tumor type who will receive an IV infusion of DS-1103a at the recommended dose for expansion (RDE) in combination with T-DXd IV Q3W starting on Cycle 1 Day 1.

Drug: DS-1103a; Drug: T-DXd

Dose Expansion (Cohort 2): DS-1103a + T-DXd

EXPERIMENTAL

Participants with a specific HER2-altered advanced solid tumor type who will receive an IV infusion of DS-1103a at the recommended dose for expansion (RDE) in combination with T-DXd IV Q3W starting on Cycle 1 Day 1.

Drug: DS-1103a; Drug: T-DXd

Interventions

DS-1103a DRUG

One IV infusion Q3W on Day 1 of each 21-day cycle

Dose Escalation: DS-1103a + T-DXd; Dose Expansion (Cohort 1): DS-1103a + T-DXd; Dose Expansion (Cohort 2): DS-1103a + T-DXd

T-DXd DRUG

One IV infusion Q3W on Day 1 of each 21-day cycle

Also known as: DS-8201a (trastuzumab derextecan), Enhertu®

Dose Escalation: DS-1103a + T-DXd; Dose Expansion (Cohort 1): DS-1103a + T-DXd; Dose Expansion (Cohort 2): DS-1103a + T-DXd

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 informed consent form (ICF), prior to the start of any study-specific qualification procedures
• Adults ≥18 years of age at the time the ICF is signed (please follow local regulatory requirements if the legal age of consent for study participation is \>18 years old)
• Pathologically documented HER2-expressing or HER2-mutated (activating mutation) solid tumor that is unresectable or metastatic
• Is willing and able to provide tumor tissue
• Presence of at least 1 measurable lesion based on computed tomography (CT) or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by investigator assessment
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Has a left ventricular ejection fraction (LVEF) ≥50% by either an echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before enrollment
• Has adequate organ and bone marrow function within 14 days before the start of study treatment. Transfusion (red blood cell or platelet) or granulocyte-colony stimulating factor (G-CSF) administration is not allowed within 14 days prior to the day on which bone marrow function is assessed, or at any time after this day and prior to Cycle 1 Day 1.
• A woman of childbearing potential (WOCBP) is eligible to participate if she is not pregnant as confirmed by highly sensitive pregnancy test and agrees to adhere to a contraceptive method that is highly effective during the Treatment Period and for at least the time needed to eliminate each study drug after the last dose.
• A male participant capable of producing sperm is eligible to participate if he agrees to adhere to the contraception methods as specified in the protocol and avoids donating sperm during the Treatment Period and for at least the time needed to eliminate each study drug.
• Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions
• Dose-escalation Phase:
• Has progressed or was non-responsive to available therapies and for which no standard or available anticancer therapy exists
• Has a pathologically documented HER2-expressing or HER2-mutated solid tumor
• Dose-expansion Phase:

You may not qualify if:

• Has had prior treatment with an anti-CD47 or anti-signal regulatory protein α (SIRPα) therapy.
• Has an inadequate treatment washout period prior to start of study treatment as specified in the protocol
• Medical history of myocardial infarction (MI) within 6 months before study enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association \[NYHA\] Class II to IV
• Has a QT interval corrected with Fridericia's formula (QTcF) prolongation to \>470 ms (females) or \>450 ms (males) based on average of the screening triplicate 12-lead electrocardiogram (ECG)
• Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening
• Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms
• Has multiple primary malignancies within 3 years. Exceptions are specified in the protocol.
• Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug products or other monoclonal antibodies
• Has an uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals
• Is requiring concomitant use of chronic systemic (IV or oral) corticosteroids or other immunosuppressive medications during the study
• Has received a live, attenuated vaccine (messenger ribonucleic acid \[mRNA\] and replication-deficient adenoviral vaccines are not considered live, attenuated vaccines) within 30 days prior to first exposure to study drug(s)
• Has substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the participant's participation in the clinical study or evaluation of the clinical study results.
• Has active or uncontrolled human immunodeficiency virus (HIV) infection as determined by plasma HIV ribonucleic acid (RNA) viral load and CD4 count.
• Has active or uncontrolled HBV or HCV. Hepatitis B and C screening testing is required. Participants are eligible only if they meet criteria as specified in the protocol.
• Has unresolved toxicities from previous anticancer therapy

Sponsors & Collaborators

• AstraZeneca: collaborator
• Daiichi Sankyo: lead

Study Sites (8)

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

RECRUITING

Lifespan Cancer Institute

Providence, Rhode Island, 02903, United States

RECRUITING

University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

NEXT Oncology

Fairfax, Virginia, 22031, United States

RECRUITING

Princess Margaret Cancer Centre, University Health Network

Toronto, M5G 2M9, Canada

RECRUITING

Oncopole - Institut Claudius Regaud

Toulouse, Haute Garonne, 31059, France

ACTIVE NOT RECRUITING

Centre Léon Bérard

Lyon, Rhone, 69373, France

ACTIVE NOT RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, 8035, Spain

RECRUITING

MeSH Terms

Interventions

trastuzumab deruxtecan

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Central Study Contacts

Contact for Clinical Trial Information

CONTACT

908-992-6400; CTRinfo@dsi.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2023
• First Posted: March 13, 2023
• Study Start: May 30, 2023
• Primary Completion (Estimated): May 15, 2030
• Study Completion (Estimated): May 15, 2030
• Last Updated: July 28, 2026

Record last verified: 2026-07

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: 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

US (4); ES (1); FR (2); CA (1)