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

Study Identifier:
DS1103-074
CT.gov Identifier:
NCT05765851
EudraCT Identifier:
202350396548
EU Trial (CTIS) Number:
2023-503965-48-00
Study Contact Information:
(210) 593-5651 or [email protected]
Will Be Recruiting

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Study Summary

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

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Breast Cancers
Non-Small Cell Lung Cancer
Solid Tumor
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I
Sex
Female & Male
Age
18+ years
Study Drug
Drug: Experimental: Dose Escalation: DS-1103a + T-DXd
Read More
Drug: Experimental: Dose Expansion (Cohort 1): DS-1103a + T-DXd
Drug: Experimental: Dose Expansion (Cohort 2): DS-1103a + T-DXd
Drug: Experimental: Dose Expansion (Cohort 3) DS-1103a + T-DXd
Study Status
Indicates the current recruitment status or the expanded access status
Will Be Recruiting

Requirements information
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 (immunohistochemistry [IHC] 1+ or greater)
  • or HER2-mutated (activating mutation) solid tumor that is unresectable or metastatic
  • (further detailed in inclusion criteria specific for Part 1 and Part 2 below)
  • - 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 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)
  • - 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:
  • - Is not amenable to standard-of-care therapy
  • - 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)
  • Dose-expansion Phase:
  • - Pathologically documented breast cancer that:
  • - Has a history of low HER2 expression, defined as IHC 2+/in situ hybridization
  • negative (ISH-) or IHC 1+ (ISH- or untested) according to American Society of
  • Clinical Oncology/College of American Pathologists (ASCO/CAP) 2018 HER2 testing
  • guidelines
  • - Is hormone receptor (HR)-positive or HR-negative (HR-positive for estrogen
  • receptor or progesterone receptor if finding of ≥1% of tumor cell nuclei are
  • immunoreactive), as defined by ASCO/CAP HR testing guidelines
  • - Has been treated with at least 1 and at most 2 prior lines of chemotherapy in the
  • recurrent or metastatic setting. If recurrence occurred within 6 months of
  • (neo)adjuvant chemotherapy, (neo)adjuvant therapy would count as 1 line of
  • chemotherapy
  • - Was never previously HER2-positive (IHC 3+ or IHC 2+/ISH+) on prior pathology
  • testing (per ASCO/CAP guidelines) or was historically HER2 IHC 0 only
  • - Was never previously treated with anti-HER2 therapy
  • - Documented radiologic progression (during or after most recent treatment)
  • ESMO 2023:
  • Part 1 (dose-escalation [based on BOIN design]) will enroll patients with pathologically documented HER2-expressing (IHC1+ or greater) or HER2-mutated (activating mutation) advanced solid tumors not amenable to standard of care. Part 2 (dose-expansion) will enroll patients with HER2-low (IHC2+/ISH- or IHC1+ [ISH- or untested]) breast cancer who received 1-2 prior lines of chemotherapy in the recurrent or metastatic setting - 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.

Clinical Study Information for Healthcare Providers

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Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START New York (Long Island)
Lake Success, NY, United States, 11042
Investigator
Geraldine O'Sullivan Coyne
Status
Will Be Recruiting
Condition(s) Treated at Site
Breast Cancers
Non-Small Cell Lung Cancer
Solid Tumor
Location
START San Antonio
San Antonio, TX, United States, 78229
Investigator
Drew Rasco
Status
Will Be Recruiting
Condition(s) Treated at Site
Breast Cancers
Non-Small Cell Lung Cancer
Solid Tumor