DESTINY-Breast07 will investigate the safety, tolerability, and anti-tumour activity of trastuzumab deruxtecan (T-DXd) in combination with other anticancer agents in patients with HER2-positive Metastatic Breast Cancer inclusive of patients with active and stable brain metastases

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

21 Jan 2021 → ongoing

Decision date (initial)

2024-06-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2023-505309-18-00

EudraCT number

2019-004531-22

ClinicalTrials.gov

NCT04538742

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety

This study is modular in design allowing assessment of safety, tolerability and anti-tumour activity of T-DXd in combination with other anti-cancer agents. Combination-treatment modules will have 2 parts: a dose-finding phase (Part 1), and a dose expansion phase (Part 2); the recommended Phase 2 dose (RP2D) determined in Part 1 will be used for the dose-expansion in Part 2.

The target population of interest in this study is patients with HER2- positive (as per ASCO/CAP 2018 guidelines) advanced/MBC. Part 1 of each module will enroll patients with locally assessed HER2-positive advanced/MBC in second-line or later patients. Part 2 of each module will enroll patients with locally assessed HER2-positive breast cancer who have not received prior treatment for advanced/metastatic disease.

Part 1: To assess the safety and tolerability, and determine RP2D for the T-DXd combinations
Part 2: To assess the safety and tolerability of T-DXd monotherapy and T-DXd combinations

Secondary objectives 1

1. Part 1 and Part 2: To assess anti-tumour activity of T-DXd combinations and T-DXd monotherapy Part 1 and Part 2: To assess the PK of T-DXd, durvalumab, pertuzumab, paclitaxel, and tucatinib, and investigate the immunogenicity of T-DXd, durvalumab, and pertuzumab

Conditions and MedDRA coding

HER2-positive Metastatic Breast Cancer

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Patients must be at least 18 years of age
2. Pathologically documented breast cancer that: a) Is advanced/unresectable (patients that can be treated with curative intent are not eligible) or metastatic b) HER2-positive (IHC 3+ or IHC 2+/ISH+) based on local assessment. The local HER2 result must be from a tumour sample obtained in the metastatic setting. c) Is documented as hormone receptor-positive (estrogen or progesterone receptor) or negative in the metastatic setting
3. Patient must have adequate tumor sample from the metastatic setting for biomarker assessment
4. ECOG Performance Status of 0 or 1
5. Part 1 a) Disease progression on or after the last systemic therapy prior to starting study treatment b) At least 1 prior treatment line in metastatic setting required.
6. Part 2 (Modules 0 - 5) a) No prior lines of therapy for advanced/MBC allowed
7. Part 2 (Module 6 and 7) a) Zero or one prior lines of therapy for advanced/MBC allowed CNS Inclusion
8. CNS Inclusion. Modules 0 - 5 Patients must have no brain metastases or stable brain metastases. Module 6 and 7 Patients must have untreated brain metastases not needing local therapy or previously treated brain metastases that have progressed since prior local therapy

Exclusion criteria 9

1. Uncontrolled or significant cardiovascular disease
2. Active or prior documented (non-infectious) ILD/pneumonitis that required steroids, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
3. Lung-specific intercurrent clinically significant illnesses
4. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
5. Spinal cord compression or a history of leptomeningeal carcinomatosis
6. Prior treatment with immune checkpoint inhibitors
7. Prior treatment with an ADC containing a topoisomerase I inhibitor
8. Prior treatment with tucatinib
9. CNS Exclusion -Modules 0 - 5: Has untreated brain metastasis -Module 6 and 7: Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of > 2 mg dexamethasone or any brain lesion thought to require immediate local therapy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part 1: AEs, SAEs, DLTs, laboratory findings
2. Part 2: AEs, SAEs, laboratory findings

Secondary endpoints 7

1. Part 1 and Part 2: ORR is defined as the proportion of patients who have a CR or PR, as determined by the Investigator at local site per RECIST 1.1.
2. Part 1 and Part 2: PFS is defined as time from the date of randomisation until the date of progression as assessed by the Investigator at local site per RECIST 1.1, or death due to any cause.
3. Part 2: PFS2 is defined as time from the date of randomisation until the date of progression on next line treatment (the earliest of the progression event subsequent to first subsequent anticancer therapy) or death; second progression will be defined according to local standard clinical practice.
4. Part 2: DoR is defined as time from the date of first documented response until the date of documented progression or death in the absence of disease progression.
5. Part 2: OS is defined as time from the date of randomisation until the date of death due to any cause.
6. Serum concentration of T-DXd, total anti-HER2 antibody, MAAA- 1181a, durvalumab, and pertuzumab; plasma concentration of paclitaxel and tucatinib
7. Immunogenicity for T-DXd, durvalumab, and pertuzumab

Investigational products

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

Test 3

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

4 EU/EEA countries · 11 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 23 files

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

Application history

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