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A Phase 1, Multicenter Trial of Subcutaneous Trastuzumab Deruxtecan in Participants with Metastatic Solid Tumors

A Study of Subcutaneous Trastuzumab Deruxtecan in Participants with Metastatic Solid Tumors

Inoguchi Akihiro

Daiichi Sankyo Co., Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

dsclinicaltrial_jp@daiichisankyo.com

Contact for Clinical Trial Information

Daiichi Sankyo Co., Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

+81-3-6225-1111

dsclinicaltrial_jp@daiichisankyo.com

Recruiting

Aug. 29, 2025

Interventional

non-randomized controlled trial

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1. Sign and date the ICF, prior to the start of any trial- specific qualification procedures.
2. Adults >=18 years or the minimum legal adult age (whichever is greater).
3. Part 1 (Dose Escalation):
Note: all HR testing and HER2 testing shall be per ASCO/CAP guidelines, respectively, in the metastatic or locally advanced setting, as applicable.

a. ER+ or ER-, HER2-positive:
adults with documented unresectable or metastatic HER2-positive BC as determined by following ASCO/CAP guideline for HER2 testing in BC, using a validated or approved test per applicable regulations, who have received a prior anti-HER2-based regimen either:
in the metastatic setting,
or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within 6 months of completing therapy.
OR

ER-, HER2-low:
Adults with documented unresectable or metastatic ER-, HER2-low (IHC 1+ or IHC 2+/ISH-) BC, as determined by following ASCO/CAP guidelines for HER2 testing in BC 2023, using a validated or approved test per applicable regulations, who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.
OR

HR+, HER2-low:
Adults who are candidates for cytotoxic systemic treatment and have pathologically documented breast cancer that:
is advanced or metastatic;
has a documented HER2-low expression (IHC 1+ or IHC 2+/ISH-), as determined by following ASCO/CAP guidelines for HER2 testing in BC 2023, using a validated or approved test per applicable regulations, in the metastatic setting;
was never previously diagnosed with HER2-positive (IHC 3+ or ISH+) disease as per ASCO/CAP guidelines.
is documented as HR+ (either ER and/or PgR positive [ER or PgR >=1%]) per ASCO/CAP guidelines in the metastatic setting. If a patient has had multiple ER/PgR results after metastatic disease, the most recent test result will be used to confirm eligibility.
has been treated with no more than 2 previous lines of chemotherapy in the recurrent or metastatic setting.
had disease progression on at least one previous line of ET with or without a targeted therapy (such as CDK4/6, mTOR or PI3-K inhibitors) administered for the treatment of metastatic disease.

Of note with regards to participants who received only one previous line of ET:
o If the one line was given while in the metastatic setting, it should have been administered with CDK4/6i to be considered a line of therapy
o If the one line was given while in the adjuvant setting, if disease recurrence occurred while on the first 24 months of adjuvant ET, that will be considered a line of therapy
o Changes in dosing schedules, or discontinuations/restarting of the same drugs or the addition of a targeted therapy to an ET without progression (eg, adding a CDK4/6 inhibitor to a current aromatase inhibitor regimen) will not be considered separate lines of therapy.

Part 2 (Dose Expansion):
Note: all HR testing and HER2 testing shall be per ASCO/CAP guidelines, respectively, in the metastatic or locally advanced setting, as applicable.

1. Adults who are candidates for cytotoxic systemic treatment and have pathologically documented breast cancer that:
is advanced or metastatic;
has a documented HER2-low expression (IHC 1+ or IHC 2+/ISH-), as determined by following ASCO/CAP guidelines for HER2 testing in BC 2023, using a validated or approved test per applicable regulations, in the metastatic setting;
was never previously diagnosed with HER2-positive (IHC 3+ or ISH+) disease as per ASCO/CAP guidelines.
is documented as HR+ (ER and/or PgR positive [ER or PgR >=1%]) per ASCO/CAP guidelines in the metastatic setting. If a patient has had multiple ER/PgR results after metastatic disease, the most recent test result will be used to confirm eligibility.
has been treated with no more than 2 previous lines of chemotherapy in the recurrent or metastatic setting.
had disease progression on at least one previous line of ET with or without a targeted therapy (such as CDK4/6, mTOR or PI3-K inhibitors) administered for the treatment of metastatic disease.

Of note with regards to participants who received only one previous line of ET:
o If the one line was given while in the metastatic setting, it should have been administered with CDK4/6i to be considered a line of therapy
o If the one line was given while in the adjuvant setting, if disease recurrence occurred while on the first 24 months of adjuvant ET, that will be considered a line of therapy
o Changes in dosing schedules, or discontinuations/restarting of the same drugs or the addition of a targeted therapy to an ET without progression (eg, adding a CDK4/6 inhibitor to a current aromatase inhibitor regimen) will not be considered separate lines of therapy.
2. At least one RECIST 1.1 measurable lesion on CT or MRI

1. Prior treatment with ADC that consists of an exatecan derivative that is a topoisomerase I inhibitor.
2. Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug products.
3. Has a history of severe hypersensitivity reactions to other monoclonal antibodies.
4. Medical history of MI within 6 months before enrollment or symptomatic CHF (New York Heart Association class II to IV). Participants with troponin levels above ULN at screening (as defined by the manufacturer), and without any MI-related symptoms should have a cardiologic consultation during the Screening Period to rule out MI.
5. Has a corrected QT interval (QTcF) prolongation to > 480 ms (regardless of participant's sex ) based on average of the screening triplicate 12-lead ECG.
6. Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.

Both

Recurrent or Metastatic Solid Tumors

Experimental: Part 1 (Dose Escalation)
Participants will receive Trastuzumab Deruxtecan subcutaneously at escalating doses.
The recommended dose for expansion (RDE) will be calculated using data collected from this population.
Dose Escalation Part: Trastuzumab Deruxtecan will be administered at escalating doses to determine the RDE.

Experimental: Part 2 (Dose Expansion)
Participants will receive Trastuzumab Deruxtecan subcutaneously at the recommended dose for expansion (RDE)
Expansion Part: Trastuzumab Deruxtecan will be administered at RDE.

Number of Participants Experiencing a Treatment Emergent Adverse Event (TEAE)
TEAEs are defined as those Adverse Events (AEs) with start or worsening date during the on-treatment period (from the first dose date of trial intervention to 21 days after the last dose date of trial intervention).
[Time Frame] From the start of trial intervention to 21 days after the last dose, up to approximately 9 months

Area Under Curve (AUC)
[Time Frame] From the start of trial intervention to last dose, up to approximately 9 months

Number of Participants with Dose limiting toxicities (DLT) During the Dose-Escalation Phase
[Time Frame] From the start of trial intervention to 21 days after the last dose, up to approximately 9 months

Percentage of Participants with Anti-Drug Antibody (ADAs)
[Time Frame] From baseline to post-baseline, up to approximately 12 months

Overall Response Rate (ORR)
ORR is defined as the proportion of participants who achieved a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), as assessed by investigator per RECIST v1.1
[Time Frame] From the enrollment/randomization date until documented disease progression, up to 12 months

Disease Control Rate (DCR)
DCR is defined as the proportion of participants with a BOR of confirmed CR, confirmed PR, or stable disease (SD) per RECIST v1.1.
[Time Frame] From the enrollment/randomization date until documented disease progression, up to 12 months

Aug. 14, 2025

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/ Supporting Information: -Study Protocol -Statistical Analysis Plan (SAP) -Informed Consent Form (ICF) 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. 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. URL: https://vivli.org/ourmember/daiichi-sankyo/

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