breastcancer metastasized breastcancer
Conditions
Interventions
All participants will receive IV T-DXd, 5.4 mg/kg, every 3 weeks (21-day
cycle). Participants may continue to receive T-DXd as long as they are
continuing to show clinical benefit, as judged by the
Sponsors
Astra Zeneca
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
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 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 = 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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Participants without BM at baseline (Cohort 1): ORR by RECIST 1.1 Participants with BM at baseline (Cohort 2): PFS by RECIST 1.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| For secondary objective 1: Participants in both cohorts: OS DoR Time to progression DoT on subsequent lines of therapy PFS2 Participants without BM at baseline (Cohort 1): Incidence of new symptomatic CNS metastasis during treatment In patients who develop isolated CNS progression, receive local therapy, and continue on protocol therapy: Time to next progression (CNS or extracranial) or death Site (CNS vs extracranial vs both) of next progression For secondary objective 2: Participants with BM at baseline (Cohort 2): ORR by RECIST 1.1 CNS PFS (time to CNS progression or death) Time to new CNS lesions ORR in brain by RECIST 1.1 as determined by ICR DoR in brain For secondary objective 3: Changes in symptoms, functioning, and HRQoL as measured by All patients: EORTC QLQ-C30, NANO scale, Cognitive Tests BM patients: MDASI brain tumor-specific items ILD/pneumonitis patients: SGRQ-I For secondary objective 4: Rate of treatment-related AEs by CTCAE Rate of investigator-assessed ILD/pneumonitis * PTs will be matched with most commonly-reported terms within ILD cluster terms * Rate of ILD clinical symptom resolution among ILD patients who have been treated with high-dose steroid (total daily dose > 2 mg dexamethasone or equivalent) Rate of AEs among patients with baseline BM who are treated with concurrent high-dose steroid (total daily dose > 2 mg dexamethasone or equivalent) For secondary objective 5: Presence of ADAs for T-DXd (confirmatory results: positive or negative, titers) | — |
Countries
Netherlands
Outcome results
None listed