Testing a new targeted therapy trastuzumab deruxtecan (DS-8201a) against ado-trastuzumab emtansine (T-DM1) for patients with advanced stage breast cancer previously treated with trastuzumab and taxane.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Daiichi Sankyo Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

23 Jan 2019 → ongoing

Decision date (initial)

2024-05-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-511204-16-00

EudraCT number

2018-000222-61

ClinicalTrials.gov

NCT03529110

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Pharmacoeconomic, Pharmacogenetic, Efficacy, Pharmacogenomic

To compare the progression-free survival (PFS) benefit of trastuzumab deruxtecan to T-DM1 for HER2-positive, unresectable and/or metastatic breast cancer subjects previously treated with trastuzumab and taxane.

Secondary objectives 1

1. Key Secondary Objective: • To compare the overall survival (OS) benefit of trastuzumab deruxtecan to T-DM1. Other Secondary Objectives: • To evaluate efficacy of trastuzumab deruxtecan compared to T-DM1 on: o Confirmed objective response rate (ORR); o Duration of response (DoR). • To further determine PK of trastuzumab deruxtecan; • To further evaluate safety of trastuzumab deruxtecan compared to TDM1; • To evaluate Health Economic and Outcomes Research (HEOR) endpoints for trastuzumab deruxtecan compared to T-DM1.

Conditions and MedDRA coding

Metastatic breast cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. • Adults ≥18 years old. (Please follow local regulatory requirements if the legal age of consent for study participation is >18 y old.) • Pathologically documented breast cancer that: - is unresectable or metastatic - has confirmed HER2 positive expression as determined according to American Society of Clinical Oncology – College of American Pathologists guidelines evaluated at a central laboratory. - was previously treated with trastuzumab and taxane in the advanced/metastatic setting or progressed within 6 mo after neoadjuvant or adjuvant treatment involving a regimen including trastuzumab and taxane. • Documented radiologic progression (during or after most recent treatment or within 6 mo after completing adjuvant therapy). • Subjects must be HER2 positive as confirmed by central laboratory assessment of most recent tumor tissue sample available. • Female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 7 mo after the last dose of trastuzumab deruxtecan and 7 mo after the last dose of T-DM1. Male subjects must agree to inform all potential female partners that they are participating in a clinical trial of a drug that may cause birth defects. Male subjects must also agree to either avoid intercourse or that they and/or any female partners of reproductive / childbearing potential will use a highly effective form of contraception during and upon completion of the study and for at least 4.5 mo after the last dose of trastuzumab deruxtecan or 4 mo after the last dose of T-DM1. • Adequate renal function, defined as: - Creatinine clearance ≥ 30 mL/min, as calculated using the Cockcroft-Gault equation • Adequate hepatic function, defined as: - Total bilirubin ≤ 1.5 × upper limit of normal (ULN) if no liver metastases or < 3 × ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline and - Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤5 × ULN.

Exclusion criteria 1

1. • Prior treatment with an anti-HER2 ADC (such as T-DM1) in the metastatic setting. Prior treatment in the adjuvant/neo-adjuvant setting would be allowed if progression of disease did not occur within 12 mo of end of adjuvant therapy. • Uncontrolled or significant cardiovascular disease, including any of the following: - History of myocardial infarction within 6 mo before randomization - History of symptomatic congestive heart failure (New York Heart Association Class II to IV) - Troponin levels consistent with myocardial infarction as defined according to the manufacturer within 28 d prior to randomization - Corrected QT interval prolongation to > 470 ms (females) or > 450 ms (male) based on average of Screening triplicate 12 lead electrocardiogram (ECG) - Left ventricular ejection fraction (LVEF) < 50% within 28 d prior to randomization • Has a history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening. • Spinal cord compression or clinically active central nervous system (CNS) metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. - Subjects with clinically inactive brain metastases may be included in the study. - Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment. • Prior participation in a study involving an antibody drug conjugate (ADC) produced by Daiichi Sankyo.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary efficacy endpoint is PFS as determined by blinded independent central review (BICR).

Secondary endpoints 1

1. The key secondary efficacy endpoint is OS.

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Daiichi Sankyo Inc.

Sponsor organisation

Daiichi Sankyo Inc.

Address

211 Mount Airy Road

City

Basking Ridge

Postcode

07920-2311

Country

United States

Scientific contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Public contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Third parties 9

Locations

4 EU/EEA countries · 35 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 34 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