Study of Trastuzumab Deruxtecan (DS-8201a, T-DXd) versus Investigator's Choice Chemotherapy in HER2-Low, Hormone Receptor Positive Breast Cancer Patients whose Disease has Progressed on Endocrine Therapy in the Metastatic Setting

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

30 Nov 2020 → ongoing

Decision date (initial)

2024-10-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB, Sweden

External identifiers

EU CT number

2024-516653-44-00

EudraCT number

2019-004493-26

ClinicalTrials.gov

NCT04494425

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess the efficacy of Trastuzumab deruxtecan (T-DXd) compared with investigator's choice chemotherapy in terms of PFS by BICR in the HR+, HER2-low (IHC 2+/ISH- and IHC 1+) populations.

Secondary objectives 9

1. Assess the efficacy of T-DXd compared with investigator's choice chemotherapy in terms of OS in HR+, HER2-low (HER2 IHC 2+/ISH- and IHC 1+) population
2. Assess the efficacy of T-DXd compared with investigator's choice chemotherapy in terms of PFS by BICR and OS in ITT (HER2 IHC>0<1+ and HER2-low) population
3. PFS by investigator assessment in the HR+ HER2-low population
4. ORR and DoR by BICR and investigator assessment in the HR+ HER2- low and ITT population
5. PFS2 according to investigator assessment, time to first subsequent treatment or death (TFST) and time to second subsequent treatment or death (TSST) in the HR+ HER2-low and the ITT population
6. Safety and tolerability of T-DXd compared to investigator's choice chemotherapy
7. PK of T-DXd
8. Symptoms, functioning and HRQoL in patients treated with T-DXd compared to investigator's choice single agent chemotherapy
9. Immunogenicity of T-DXd

Conditions and MedDRA coding

HER2-Low, Hormone Receptor Positive Breast Cancer which has Progressed on Endocrine Therapy in the Metastatic Setting.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patients must be ≥18 years of age.
2. Pathologically documented breast cancer that: a. is advanced or metastatic b. Has a history of HER2-low or negative expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) or IHC 0 (ISH- or untested) c. Has HER2-low expression or HER2 IHC >0 <1+ expression as determined by the central laboratory result from a metastatic setting d. was never previously HER2-positive e. has documented HR+ disease in the metastatic disease setting.
3. Has adequate tumor samples for assessment of HER2 status
4. Disease progression on at least 2 previous lines of endocrine therapy with or without a targeted therapy (Progression of disease within 24 months on adjuvant ET is considered a line of therapy) or disease progression on endocrine therapy + CDK4/6 inhibitor within 6 months of starting first line treatment for metastatic disease and considered appropriate for chemotherapy as the next treatment by the investigator.
5. No prior chemotherapy for advanced or metastatic breast cancer.
6. Has protocol-defined adequate organ and bone marrow function. The most recent results must be used to meet this inclusion criteria

Exclusion criteria 7

1. Ineligible for all options in the investigator's choice chemotherapy arm. Patients with contraindications to capecitabine, paclitaxel, and nabpaclitaxel treatment, per local prescribing information, cannot be enrolled
2. Uncontrolled intercurrent illness or significant cardiovascular disease
3. Active or prior documented ILD/pneumonitis that required steroids or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
4. Lung-specific intercurrent clinically significant illnesses
5. Patients with spinal cord compression or active clinically central nervous system metastasis.
6. Concurrent enrolment in another clinical study, unless it is: - an observational (non-interventional) clinical study - during the follow up period of a prior interventional study (prescreening for this study while a patient is on treatment in another clinical study is acceptable)
7. Have received a study treatment from a prior interventional study, administered in the last 30 days prior to first dose of this study treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS by BICR according to RECIST 1.1 in the HR+, HER2-low population

Secondary endpoints 11

1. Overall Survival (OS) - in HR+ HER2-low population
2. Progression Free Survival (PFS) - in intent to treat (ITT) population (HER2 IHC >0 <1+ and HER2-low)
3. OS - in ITT population (HER2 IHC >0 <1+ and HER2-low)
4. Objective Response Rate (ORR) and Duration of response (DoR) - in HR+, HER-2 low population
5. PFS by Investigator assessment - in the HR+, HER2-low population
6. ORR and DoR - in the ITT population
7. PFS2 by Investigator assessment, time to first subsequent therapy (TFST) and time to second subsequent treatment or death (TSST) - in HR+, HER2-low and the ITT population
8. Safety and tolerability of T-DXd compared to chemotherapy
9. The pharmacokinetics (PK) of T-Dxd
10. Health-related quality of life
11. Immunogenicity of T-Dxd

Investigational products

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

Test 1

Comparator 4

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

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

12 EU/EEA countries · 79 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 98 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