An Open-Label, Multinational, Multicenter, Phase 3b/4 Study of Trastuzumab Deruxtecan in Patients With or Without Baseline Brain Metastasis With Previously-Treated Advanced/Metastatic HER2-Positive Breast Cancer (DESTINY-Breast12)

Phase 3

Completed

• Conditions: breastcancer; metastasized breastcancer; 10006291

• Registration Number: NL-OMON51877
• Lead Sponsor: Astra Zeneca

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 24 June 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 26

Inclusion Criteria

Key inclusion Criteria:
1. Pathologically documented breast cancer that:
(a) Is unresectable/advanced or metastatic, and
(b) Has confirmed HER2-positive status as determined according to ASCO/CAP
guidelines (Wolff et al, 2018) evaluated at a local laboratory
2. Participant must have either:
(a) No evidence of BM, or
(b) Untreated BM on screening contrast brain MRI / CT scan
(i)not needing immediate local therapy, or
(ii)For participants with untreated CNS lesions: if lesion <= 2.0 cm no
discussion with study physician is required prior to enrolment, if lesion is
>2.0 cm discussion with and approval from the study physician is required prior
to enrollment, or
(c) Previously treated stable or progressing BM
(i) Previously treated BM with local therapy may either be
radiographically stable for >= 4 weeks since completion of treatment or may
have progressed since prior local CNS therapy, provided that there is no
clinical indication for immediate re-treatment with local therapy
(ii) Patients treated with CNS local therapy for newly identified
lesions found on contrast brain MRI/CT scan performed during screening for
this study who also have other sites of disease assessable by RECIST 1.1
3. Participants with BMs must be neurologically stable and:
(a) Be receiving the equivalent of dexamethasone <= 3 mg/day if treatment is
required
(b) If receiving an anticonvulsant regimen, the regimen must have been
stable for >= 14 days before first day of dosing
(c) Relevant records of any CNS treatment must be available to allow for
classification of TLs and NTLs
4. Previous breast cancer treatment:
(a) Radiologic or objective evidence of disease progression on or after HER2
targeted therapies.
Note: Disease progression within 6 months after adjuvant treatment with HER2
targeted therapies is also acceptable.
(b) No more than 2 lines/regimens of therapy in the metastatic setting.
Note: A line/regimen of treatment should be counted based on a progression
event.

Exclusion Criteria

1. Known or suspected LMD 2. Prior exposure to tucatinib treatment 3. Based on
screening contrast brain MRI/ CT scan, participants must not have any of the
following: (a) Any untreated brain lesions > 2.0 cm in size (b) Ongoing use of
systemic corticosteroids for control of symptoms of BMs at a total daily dose
>3 mg of dexamethasone (or equivalent). (c) Any brain lesion thought to require
immediate local therapy, (d) Have poorly controlled (> 1/week) generalized or
complex partial seizures, or manifest neurologic progression due to BMs
notwithstanding CNS-directed therapy 4. Has spinal cord compression

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Participants without BM at baseline (Cohort 1):<br /><br>ORR by RECIST 1.1<br /><br>Participants with BM at baseline (Cohort 2):<br /><br>PFS by RECIST 1.1</p><br>