Advanced Solid TumorPhase 1NCT05765851
A Study of DS-1103a Combination Therapy in Participants With Advanced Solid Tumors
A Phase 1 study testing DS-1103a and T-DXd in people with Advanced Solid Tumor, run by Daiichi Sankyo at 13 sites in 5 countries.
Trial summary
This study will evaluate the safety and efficacy of DS-1103a combination therapy in participants with advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor
- What is being tested?
- DS-1103a and T-DXd
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 128 participants
- Where
- 13 sitesin 5 countries
- Study dates
- 30 May 2023to 28 Feb 2031
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
13 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
13 sites in 5 countries
United States5 sites, 5 recruiting
- Recruiting
NEXT Oncology
Fairfax, Virginia, 22031
Principal Investigator
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Principal Investigator
- Recruiting
Lifespan Cancer Institute
Providence, Rhode Island, 02903
Principal Investigator
- Recruiting
University of Utah
Salt Lake City, Utah, 84112
Principal Investigator
- Recruiting
Florida Cancer Specialists
Sarasota, Florida, 34232
Principal Investigator
Japan4 sites, 4 recruiting
- Recruiting
Gifu University Hospital
Gifu, 501-1194
Principal Investigator
- Recruiting
Shizuoka Cancer Center
Nakatogari, 411-8777
Principal Investigator
- Recruiting
The University of Osaka Hospital
Osaka, 565-0871
Principal Investigator
- Recruiting
The Cancer Institute Hospital Of JFCR
Tokyo, 135-8550
Principal Investigator
France2 sites, 2 recruiting
- Recruiting
Centre Léon Bérard
Lyon, 69373
Principal Investigator
- Recruiting
Oncopole - Institut Claudius Regaud
Toulouse, 31059
Principal Investigator
Canada1 site, 1 recruiting
- Recruiting
Princess Margaret Cancer Centre, University Health Network
Toronto, M5G 2M9
Principal Investigator
Spain1 site, 1 recruiting
- Recruiting
Hospital Universitari Vall d'Hebron
Barcelona, 8035
Principal Investigator
About this study
Official title: 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.
Read the 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.
- Conditions
- Advanced Solid Tumor
- Being tested
- DS-1103a, T-DXd
- Keywords
- Advanced Solid Tumor, DS-1103a, CD47, SIRPa
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DS-1103aDrug
One IV infusion Q3W on Day 1 of each 21-day cycle
T-DXdDrug
Also called DS-8201a (trastuzumab derextecan), Enhertu®
One IV infusion Q3W on Day 1 of each 21-day cycle
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: DS-1103a; Drug: T-DXd |
| Dose Expansion (Cohort 3) 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. Receives: Drug: DS-1103a; Drug: T-DXd |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Dose-limiting Toxicities (Dose Escalation)
Measured: 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)
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.
Measured: 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)
Measured: 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)
Measured: Screening through long-term follow up, up to approximately 91 months
Secondary outcomes (10)
Overall Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events (Dose Expansion)
Measured: Screening through long-term follow up, up to approximately 5 years 11 months
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2023
- Study start30 May 2023
- Primary completion31 May 2029 (estimated)
- Study completion28 Feb 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- More trials run by Daiichi SankyoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 128 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Global Clinical Leader, Study director, Daiichi Sankyo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05765851
- Sponsor's protocol ID
- DS1103-074
- Other IDs
- 2023-503965-48-00, jRCT2031260255, 2023
- Status last verified
- Oct 2026
- First submitted
- 1 Mar 2023
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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/