A study to investigate the efficacy and safety of trastuzumab deruxtecan in patients With or Without Brain Metastasis Who Have Previously-Treated Advanced or Metastatic HER2 Positive Breast Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Jun 2021 → ongoing

Decision date (initial)

2024-09-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2024-510588-53-00

EudraCT number

2020-005048-46

ClinicalTrials.gov

NCT04739761

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To describe the overall treatment effect of T DXd in HER2-positive MBC patients with or without baseline BM

Secondary objectives 4

1. To describe the treatment effect on the development and progression of BM in patients with or without baseline BM using additional efficacy measurements
2. To describe efficacy in patients with stable or untreated BM
3. To describe the effect of T-DXd on symptoms, functioning, and HRQoL in HER2-positive MBC patients with or without baseline BM
4. To describe the safety profile of T-DXd

Conditions and MedDRA coding

Treatment of patients with HER2-positive breast cancer with or without brain metastasis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

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 cm, no discussion with study physician is required prior to enrollment- 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 4

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 of > 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. •Participants without BM at baseline (Cohort 1): ORR by RECIST 1.1 per ICR • Participants with BM at baseline (Cohort 2): PFS by RECIST 1.1 per ICR

Secondary endpoints 4

1. • Both cohorts: - OS; - DoR (RECIST ICR); - Time to progression (RECIST ICR); - DoT on subsequent therapy lines; - PFS2. • Cohort 1 only: - Incidence of new symptomatic CNS metastasis during treatment. • In patients with 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.
2. Participants with BM at baseline (Cohort 2): - ORR by RECIST 1.1 per ICR; - CNS PFS by CNS RECIST 1.1 per ICR; - Time to new CNS lesions; - CNS ORR by CNS RECIST 1.1 per ICR; - CNS DoR by CNS RECIST 1.1 per ICR
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
4. Safety and tolerability will be evaluated in terms of AEs, vital signs, clinical laboratory results, and ECGs, rate of investigator-assessed ILD/pneumonitis, and rate of AEs among patients with baseline BM who are treated with concurrent high-dose steroid (total daily dose > 2 mg dexamethasone or equivalent)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

Clinical Study Information Centre

Public contact point

Organisation

AstraZeneca AB

Contact name

Clinical Study Information Centre

Third parties 1

Locations

8 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 80 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications