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

Phase 1

Not yet recruiting

• Conditions: Recurrent or Metastatic Solid Tumors
• Interventions: Drug: Trastuzumab Deruxtecan

• Registration Number: NCT07015697
• Lead Sponsor: Daiichi Sankyo

Brief Summary

This is a dose escalation, and dose expansion study of T-DXd plus hyaluronidase administered subcutaneously, to assess the safety, tolerability, PK and efficacy of SC T-DXd plus hyaluronidase in participants with metastatic solid tumors.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-03
• Study First Submitted QC: 2025-06-03
• Last Update Submitted: 2025-06-03
• Study First Posted: 2025-06-11
• Last Update Posted: 2025-06-11
• Study Start: 2025-06-30
• Primary Completion: 2028-12-31
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 76

Inclusion Criteria

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):

   1. 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 guidelines9 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:

      • 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
      • 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
      • 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):

   <!-- -->

   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 guidelines9 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:

      • 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
      • 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
      • 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

Key

Exclusion Criteria

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 > 450 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 1 (Dose Escalation)	Trastuzumab Deruxtecan	Participants will receive Trastuzumab Deruxtecan subcutaneously at escalating doses. The recommended dose for expansion (RDE) will be calculated using data collected from this population.
Part 2 (Dose Expansion)	Trastuzumab Deruxtecan	Participants will receive Trastuzumab Deruxtecan subcutaneously at the recommended dose for expansion (RDE)

Primary Outcome Measures

Name	Time	Method
Number of Participants Experiencing a Treatment Emergent Adverse Event (TEAE)	From the start of trial intervention to 21 days after the last dose, up to approximately 9 months	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).
Area Under Curve (AUC)	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	From the start of trial intervention to 21 days after the last dose, up to approximately 9 months

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants with Anti-Drug Antibody (ADAs)	From baseline to post-baseline, up to approximately 12 months
Overall Response Rate (ORR)	From the enrollment/randomization date until documented disease progression, up to 12 months	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
Disease Control Rate (DCR)	From the enrollment/randomization date until documented disease progression, up to 12 months	DCR is defined as the proportion of participants with a BOR of confirmed CR, confirmed PR, or stable disease (SD) per RECIST v1.1.