RecruitingPhase 1NCT05765851

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


Sponsor

Daiichi Sankyo

Enrollment

108 participants

Start Date

May 30, 2023

Study Type

INTERVENTIONAL

Conditions

Summary

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


Eligibility

Min Age: 18 Years

Inclusion Criteria17

  • 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 Criteria23

  • 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

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Interventions

DRUGDS-1103a

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

DRUGT-DXd

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


Locations(8)

Florida Cancer Specialists

Sarasota, Florida, United States

Lifespan Cancer Institute

Providence, Rhode Island, United States

University of Utah

Salt Lake City, Utah, United States

NEXT Oncology

Fairfax, Virginia, United States

Princess Margaret Cancer Centre, University Health Network

Toronto, Canada

Oncopole - Institut Claudius Regaud

Toulouse, Haute Garonne, France

Centre Léon Bérard

Lyon, Rhone, France

Hospital Universitari Vall d'Hebron

Barcelona, Spain

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NCT05765851


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