Trastuzumab deruxtecan (T-DXd) with or without Pertuzumab versus Taxane, Trastuzumab and Pertuzumab as First-line Treatment in HER2-positive, Metastatic 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

27 May 2021 → ongoing

Decision date (initial)

2024-06-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2023-505249-24-00

EudraCT number

2020-004074-21

ClinicalTrials.gov

NCT04784714

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy, Pharmacogenetic, Pharmacokinetic, Dose response

To assess the efficacy of T-DXd ± pertuzumab compared with THP in terms of PFS according to BICR in participants with HER2-positive, first-line mBC.

Secondary objectives 8

1. To assess the efficacy of T-DXd ± pertuzumab relative to THP by assessment of PFS according to investigator assessment in participants with HER2-positive, first-line mBC.
2. To assess the efficacy of T-DXd ± pertuzumab relative to THP in terms of OS in participants with HER2-positive, first-line mBC.
3. To assess the efficacy of T-DXd ± pertuzumab relative to THP by assessment of ORR and DoR according to BICR and investigator assessment in participants with HER2-positive, first-line mBC.
4. To assess the efficacy of T-DXd ± pertuzumab relative to THP by assessment of PFS2 according to investigator assessment in participants with HER2-positive, first-line mBC.
5. To assess the effect of T-DXd ± pertuzumab relative to THP in terms of patient-reported pain in participants with HER2-positive, first-line mBC.
6. To assess patient-reported treatment tolerability.
7. To assess the PK of T-DXd and pertuzumab.
8. To investigate the immunogenicity of T-DXd.

Conditions and MedDRA coding

HER2-positive metastatic breast cancer

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Patients must be ≥18 years of age
2. Pathologically documented breast cancer that: 1. is advanced or metastatic 2. is locally assessed and prospectively centrally confirmed as HER2-positive (IHC3+ or ISH+) 3. is documented by local testing as hormone receptor (HR)-positive or HR-negative disease in the metastatic setting
3. No prior chemotherapy or HER2-targeted therapy for advanced or metastatic breast cancer or only 1 previous line of endocrine therapy in the metastatic setting. Participants who have received chemotherapy or HER2-targeted therapy in the neo-adjuvant or adjuvant setting are eligible if > 6 months from treatment to metastatic diagnosis.
4. Has protocol-defined adequate organ and bone marrow function
5. ECOG performance status 0 or 1

Exclusion criteria 5

1. Ineligible for any of the agents on the study.
2. Any substance abuse or other medical conditions that, in the investigator's opinion, may interfere with subject's participation or study results
3. Patients with spinal cord compression or clinically active central nervous system metastases. Participants with clinically inactive brain metastases or treated brain metastases that are no longer symptomatic may be included in the study.
4. Active or prior documented interstitial lung disease (ILD)/pneumonitis or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
5. Prior randomization or treatment in a previous trastuzumab deruxtecan study regardless of treatment arm assignment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS is defined as the time from date of randomisation until the date of objective radiological disease progression according to BICR using RECIST 1.1 or death by any cause.

Secondary endpoints 8

1. PFS is defined as the time from date of randomisation until the date of objective radiological disease progression according to investigator assessment using RECIST 1.1 or death by any cause.
2. OS is defined as the time from randomisation until the date of death due to any cause.
3. ORR is defined as the proportion of participants who have a CR or PR, as determined by BICR and investigator assessment per RECIST 1.1. DoR is defined as the time from date of first detection of objective response until the date of objective radiological disease progression according to BICR and investigator assessment using RECIST 1.1 or death in the absence of progression.
4. Time to second progression or death (PFS2) by Investigator assessment
5. Health related quality of life (HRQoL) using the European Organisation for Research and Treatment of Cancer (EORTC)
6. Serum concentration of trastuzumab deruxtecan and pertuzumab
7. Immunogenicity of trastuzumab deruxtecan, alone or with pertuzumab.
8. Safety and tolerability of trastuzumab deruxtecan, alone or with pertuzumab

Investigational products

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

Test 1

Comparator 4

Placebo 1

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

Study information Centre

Public contact point

Organisation

AstraZeneca AB

Contact name

Study information Centre

Third parties 9

Locations

9 EU/EEA countries · 61 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 61 files

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

Application history

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