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

A Phase 1, 2-Part, Multicenter, First-In-Human Dose-Escalation and Dose-Expansion Study of DS-1103a Combination Therapy in Subjects With Advanced Solid Tumors

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

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: DS-1103a; Drug: T-DXd

Detailed Description

DS-1103a, a recombinant humanized IgG4 anti-SIRPα antibody designed to block the SIRPα-CD47 interaction, is being developed for the treatment of advanced cancers in combination with other anticancer therapies. This is the first-in-human, dose-escalation and dose-expansion clinical study designed to assess the safety and efficacy of DS-1103a combination therapy in participants with advanced solid tumors.

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Toronto, Canada, M5G 2M9
    • Princess Margaret Cancer Centre, University Health Network
• France
  • Haute Garonne
    • Toulouse, Haute Garonne, France, 31059
      • Oncopole - Institut Claudius Regaud
  • Rhone
    • Lyon, Rhone, France, 69373
      • Centre Léon Bérard
• Spain
  • Barcelona, Spain, 8035
    • Hospital Universitari Vall d'Hebron
• United States
  • Florida
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Lifespan Cancer Institute
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • NEXT Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 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
• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: DS-1103a; One IV infusion Q3W on Day 1 of each 21-day cycle; Drug: T-DXd; One IV infusion Q3W on Day 1 of each 21-day cycle; Other Names: DS-8201a (trastuzumab derextecan); Enhertu®
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.	Drug: DS-1103a; One IV infusion Q3W on Day 1 of each 21-day cycle; Drug: T-DXd; One IV infusion Q3W on Day 1 of each 21-day cycle; Other Names: DS-8201a (trastuzumab derextecan); Enhertu®
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.	Drug: DS-1103a; One IV infusion Q3W on Day 1 of each 21-day cycle; Drug: T-DXd; One IV infusion Q3W on Day 1 of each 21-day cycle; Other Names: DS-8201a (trastuzumab derextecan); Enhertu®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate Assessed by Investigator (Dose Escalation and 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 the Investigator per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.	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)	Disease control rate is defined as the proportion of participants with a best overall response of confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) as assessed by the Investigator (Dose Escalation and Dose Expansion) and Blinded independent Central Review (BICR)(Dose Expansion) per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.	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)	Clinical benefit rate (CBR) is defined as the proportion of participants with a best overall response of confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) lasting ≥183 days as assessed by the Investigator (Dose Escalation and Dose Expansion) and Blinded Independent Central Review (BICR) (Dose Expansion) per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.	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)	Duration of response (DoR) in a responding participant is defined as the time from the date of the first documentation of objective response (confirmed complete response [CR] or confirmed partial response [PR]) to the date of the first radiographic disease (as assessed by the Investigator [Dose Escalation and Dose Expansion] and Blinded Independent Central Review (BICR) [Dose Expansion]) per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurs first.	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)	Area under the plasma concentration-time curve up to the last quantifiable time (AUClast) and Area under the plasma concentration-time curve during dosing interval (AUCtau) will be assessed using non-compartmental methods.	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)
Pharmacokinetic Parameter Maximum Plasma Concentration for DS-1103a (Dose Escalation and Dose Expansion)	Maximum plasma concentration (Cmax) will be assessed using non-compartmental methods.	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)
Pharmacokinetic Parameter Time to Maximum Plasma Concentration for DS-1103a (Dose Escalation and Dose Expansion)	Time to maximum plasma concentration (Tmax) will be assessed using non-compartmental methods.	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)
Pharmacokinetic Parameter Minimum Plasma Concentration for DS-1103a (Dose Escalation and Dose Expansion)	Minimum plasma concentration (Cmin) will be assessed using non-compartmental methods.	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)
Number of Participants With Treatment-emergent Anti-drug Antibodies(ADAs) (Dose Escalation and Dose Expansion)		Cycle 1 (D1, D15), Cycle 2 (D1, D15 [Dose Escalation only]), Cycles 3 and 4 (D1), thereafter every 2 cycles (D1), EOT, 40-day and 3-month (mth) follow-up (FU). ADA collection will occur as specified in protocol if pts are ADA positive at 3 mths.

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2023
• Primary Completion (Estimated): May 15, 2030
• Study Completion (Estimated): May 15, 2030

Study Registration Dates

• First Submitted: March 1, 2023
• First Submitted That Met QC Criteria: March 1, 2023
• First Posted (Actual): March 13, 2023

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Advanced Solid Tumor; CD47; SIRPa; DS-1103a
• Additional Relevant MeSH Terms: Neoplasms by Site; Skin Diseases; Breast Diseases; Neoplasms; Breast Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Immunoconjugates; trastuzumab deruxtecan
• Other Study ID Numbers: DS1103-074; 2023-503965-48-00 (Other Identifier: EU CT)

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