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

NCT05765851 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: DS1103-0742023-503965-48-00
• Study Type: interventional
• Target: 78
• Locations: 4 countries
• Sites: 8

Brief Summary

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

Conditions

Advanced Solid Tumor; Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Number of Participants with Dose-limiting Toxicities Following DS-1103a Combination Therapy (Dose Escalation)

  From Cycle 1 Day 1 up to 3-month safety follow up (each cycle is 21 days)

• Overall Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events Following DS-1103a Combination Therapy (Dose Expansion)

  Screening (Day -28 to 0) through long-term follow up, up to approximately 44 months

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

  Confirmed objective response rate (ORR) is defined as the sum of the complete response (CR) rate and partial response (PR) rate based on blinded independent central review (BICR) by Response Evaluation Criteria In Solid Tumors v1.1 and confirmed by a second assessment.

  Baseline up until documented progressive disease, unacceptable toxicity, death, lost to follow-up, or withdrawal by the participant, up to approximately 44 months

Secondary Outcomes (9)

• Number of Participants With Objective Response Rate Assessed by Investigator Following DS-1103a Combination Therapy (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 44 months

• Disease Control Rate Following DS-1103a Combination Therapy Assessed by Investigator (Dose Escalation) or 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 44 months

• Clinical Benefit Rate Following DS-1103a Combination Therapy (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 44 months

• Duration of Response Following DS-1103a Combination Therapy (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 44 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 5 and beyond Day 1; Dose Expansion: Cycles 1 and 3: Days 1,2,4,8,15; Cycle 2 Days 1,8,15; Cycle 4 and beyond Day 1 (each cycle is 21 days)

Study Arms (2)

Dose Escalation: DS-1103a + T-DXd

EXPERIMENTAL

Participants with HER2-expressing or HER2-mutant advanced metastatic solid tumors who will receive an 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 Q3W at a dose of 5.4 mg/kg.

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

Dose Expansion: DS-1103a + T-DXd

EXPERIMENTAL

Participants with HER2-low expressing breast cancer who will receive an IV infusion of DS-1103a at the recommended dose for expansion (RDE) in combination with T-DXd 5.4 mg/kg 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: 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: 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)
• Is willing and able to provide adequate baseline tumor samples. If an adequate archival tumor tissue is not available, a fresh tumor tissue biopsy is required
• 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 28 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 start of study treatment.
• If the participant is a female of childbearing potential, she must have a negative serum pregnancy test at Screening and must be willing to use highly effective birth control upon enrollment, during the Treatment Period, and for at least 10 months following the last dose of study drug(s).
• If male, the participant must be surgically sterile or their female partner of childbearing potential must be willing to use highly effective birth control upon enrollment, during the Treatment Period, and for 6 months following the last dose of study drug(s). In addition to the above, it is recommended that the male participant uses a condom throughout this period to prevent their partner from possibly being exposed to the study drug(s) via sperm.
• Male participants must not freeze or donate sperm from the time of enrollment, during the Treatment Period, and for at least 6 months after the final study drug(s) administration
• Female participants must not donate, or retrieve for their own use, ova from the time of enrollment, during the Treatment Period, and for at least 10 months after the final study drug(s) administration
• 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 (eg, breast cancer) or HER2-mutated (eg, non-small cell lung cancer \[NSCLC\]) solid tumor (participants with gastric cancer or gastroesophageal junction adenocarcinoma are not eligible)

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, defined as follows:
• Major surgery: ≤4 weeks or ≤2 weeks for low-invasive cases (eg, colostomy)
• Radiation therapy including palliative stereotactic radiation to chest: ≤4 weeks
• Palliative stereotactic radiation therapy to other anatomic areas: ≤2 weeks
• Received any systemic agent from a previous treatment regimen or clinical study within the specified time frame prior to administration 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, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, other solid tumors curatively treated, or contralateral breast cancer
• 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)

Sponsors & Collaborators

• Daiichi Sankyo: lead
• AstraZeneca: collaborator

Study Sites (8)

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Lifespan Cancer Institute

Providence, Rhode Island, 02903, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

NEXT Oncology

Fairfax, Virginia, 22031, United States

Location

Princess Margaret Cancer Centre, University Health Network

Toronto, M5G 2M9, Canada

Location

Oncopole - Institut Claudius Regaud

Toulouse, Haute Garonne, 31059, France

Location

Centre Léon Bérard

Lyon, Rhone, 69373, France

Location

Hospital Universitari Vall d'Hebron

Barcelona, 8035, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• 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): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: May 11, 2025

Record last verified: 2025-05

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