Recruiting
Phase 1

DS-1103a

Sponsor:

Daiichi Sankyo

Code:

NCT05765851

Conditions

Advanced Solid Tumor

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

DS-1103a

T-DXd

Study Details

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

Study ID

NCT05765851

Start date

May 30, 2023

Status verified date

Oct, 2026

Completion date

Feb 28, 2031

Anticipated

Primary completion date

May 31, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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:

  • Has pathologically documented specific HER2 altered advanced solid tumor type
  • Has received prior therapy as specified in the protocol

Exclusion Criteria:

  • 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. Subjects with a positive/reactive HIV antibody and/or known HIV infection at Screening must be tested for HIV RNA viral load and CD4+ T-cell count during the Screening Period (if acceptable by local regulations or IRBs/IECs) and are eligible if certain criteria are met as specified in the protocol.
  • 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
  • Female who is pregnant, breastfeeding, or planning to become pregnant
  • Has lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder
  • Any autoimmune, connective tissue or inflammatory disorders
  • Prior complete pneumonectomy
  • Any of the following within 6 months of enrollment: Cerebrovascular accident, transient ischemic attack, or other arterial thromboembolism event
  • Psychological, social, familial, or geographical factors that would prevent regular follow-up
  • Any active or chronic corneal disorders, other active ocular conditions requiring ongoing therapy, or any clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy
  • Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg) and/or severe arrhythmia within 28 days before enrollment

Dose Expansion (Phase 2)

  • Has had prior treatment with antibody-drug conjugate that consists of an exatecan derivative that is a topoisomerase I inhibitor including prior participation in a study involving an antibody-drug conjugate produced by Daiichi Sankyo and/or AstraZeneca.

Study Design

Enrollment

128 participants

Anticipated

Allocation

Non randomized

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Dose Escalation: DS-1103a + T-DXd

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.

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

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.

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

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.

experimental: Dose Expansion (Cohort 3) DS-1103a + T-DXd

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.

Interventions

DS-1103a

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

T-DXd

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

Primary outcome measure

  • Number of Participants with Dose-limiting Toxicities (Dose Escalation) [ Time Frame: From Cycle 1 Day 1 to Cycle 2 Day 21 (each cycle is 21 days) ]
  • Objective Response Rate Assessed by Blinded Independent Central Review Following DS-1103a Combination Therapy (Dose Expansion) [ Time Frame: 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 ]
  • Number of Participants with Dose-limiting Toxicities Following DS-1103a Combination Therapy (Dose Expansion; Cohort 2 Safety Run In and Japanese Population Tolerability Assessments) [ Time Frame: 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 Expansion; Cohort 2 Safety Run In and Japanese Population Tolerability Assessments) [ Time Frame: Screening through long-term follow up, up to approximately 91 months ]

Central Contacts and Locations

Central contacts

Contact for Clinical Trial Information

908-992-6400CTRinfo@dsi.com

Locations

Florida Cancer Specialists

Recruiting

Sarasota, Florida, United States, 34232

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Lifespan Cancer Institute

Recruiting

Providence, Rhode Island, United States, 02903

University of Utah

Recruiting

Salt Lake City, Utah, United States, 84112

NEXT Oncology

Recruiting

Fairfax, Virginia, United States, 22031

Princess Margaret Cancer Centre, University Health Network

Recruiting

Toronto, Canada, M5G 2M9

More Information

Sponsor

Daiichi Sankyo

Last update posted

Oct 22, 2026

Last verified

Oct, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-24. This information was provided to ClinicalTrials.gov by Daiichi Sankyo on 2026-10-22. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.