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

Daiichi Sankyo

Status and phase: Enrolling; Phase 1

Conditions: Recurrent or Metastatic Solid Tumors

Treatments: Drug: Trastuzumab Deruxtecan

Study type: Interventional

Funder types: Industry

Identifiers

NCT07015697

DS8201-801

Details and patient eligibility

About

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.

Enrollment: 76 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key 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):

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:

• 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):

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:

   • 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 > 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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76 participants in 2 patient groups

Part 1 (Dose Escalation)

Experimental group

Description:

Participants will receive Trastuzumab Deruxtecan subcutaneously at escalating doses. The recommended dose for expansion (RDE) will be calculated using data collected from this population.

Treatment:

Drug: Trastuzumab Deruxtecan

Part 2 (Dose Expansion)

Experimental group

Description:

Participants will receive Trastuzumab Deruxtecan subcutaneously at the recommended dose for expansion (RDE)

Treatment:

Drug: Trastuzumab Deruxtecan