Real-world Study of Trastuzumab Deruxtecan in Patients With Unresectable or Metastatic HER2-low Breast Cancer (EXPLORE)

REal-world Study of Trastuzumab deruXtecan in Patients With unresectabLe or Metastatic Breast Cancer Expressing HER2-lOw From BulgaRia and SlovEnia (EXPLORE)

A longitudinal, non-interventional study with trastuzumab deruxtecan for patients with HER2-low expressing unresectable or metastatic breast cancer in Bulgaria and Slovenia

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: trastuzumab deruxtecan

Detailed Description

EXPLORE Non-Interventional Study for HER2-low Breast Cancer Treatment with T-DXd

Background:

HER2 is a prognostic marker in various cancers, including breast cancer (BC). Traditionally categorized as HER2-positive or HER2-negative, recent advancements with anti-HER2 ADCs, like trastuzumab deruxtecan (T-DXd), have shown benefits for HER2-low status BC. The DB-04 trial demonstrated significant survival benefits with T-DXd, leading to its EMA approval for HER2-low BC in January 2023.

Study Rationale:

Limited real-world evidence exists for T-DXd in HER2-low BC, particularly in the Balkans. The EXPLORE study aims to fill this gap by collecting real-world data in Bulgaria and Slovenia.

Objectives:

Primary Objective:

Describe real-world Time to Next Treatment (rwTTNT1) of T-DXd in HER2-low unresectable or metastatic BC (mBC).

Secondary Objectives:

Describe pre-T-DXd treatment patterns at baseline. Describe patient demographics and clinical characteristics at baseline. Describe rwTTNT1 by prior therapy lines in the metastatic setting and by hormone receptor (HR) status.

Evaluate real-world Time to Treatment Discontinuation (rwTTD1).

Exploratory Objectives:

Evaluate real-world progression-free survival (rwPFS1). Characterize subsequent treatments and post-progression endpoints (rwTTNT2, rwTTD2, rwPFS2).

Describe biopsy patterns. Evaluate reasons for discontinuation (rwTTNT1 and rwTTNT2). Describe T-DXd treatment changes over time. No formal hypothesis is set.

Methods:

Study Design:

Observational, longitudinal, non-interventional study in Bulgaria and Slovenia. Patients with unresectable or mBC starting T-DXd within 30 days of enrolment. Data from hospital charts at routine visits.

Population:

Adults (≥18 years) with HER2-low mBC, initiating T-DXd independent of the study.

Exposure:

T-DXd treatment details (dose, duration) and other therapies recorded. Recommended T-DXd dose: 5.4 mg/kg IV every 3 weeks.

Outcomes:

Primary: Time from T-DXd initiation to subsequent therapy or death. Exploratory: Various survival measures, biopsy patterns, reasons for discontinuation, and treatment changes.

Sample Size:

Approximately 135 patients (100 in Bulgaria, 35 in Slovenia).

Statistical Analysis:

Descriptive analyses for cohort characteristics. Kaplan-Meier method for time-to-event endpoints. Subgroup analyses by prior therapy lines and HR status.

Data Collection:

Data from paper or electronic health records. Single anonymized dataset via electronic case report forms (CRFs).

• Study Type: Observational
• Enrollment (Estimated): 135

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center, Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Bulgaria
  • Burgas, Bulgaria, 8000
    • Recruiting
    • Research Site
    • Contact: Phone Number: +35956 531068; Email: odisp@abv.bg
    • Principal Investigator: Ivan Bivolarski, Dr.
  • Plovdiv, Bulgaria, 4004
    • Not yet recruiting
    • Research Site
    • Contact: Phone Number: +35932277240; Email: kocplovdiv@onkoplov.com
    • Principal Investigator: Ivan Tonev, Dr.
  • Sofia, Bulgaria, 1407
    • Not yet recruiting
    • Research Site
    • Contact: Phone Number: +35924034000
    • Principal Investigator: Jeliazko Arabadjiev
  • Sofia, Bulgaria, 1330
    • Active, not recruiting
    • Research Site
  • Sofia, Bulgaria, 1618
    • Not yet recruiting
    • Research Site
    • Contact: Phone Number: +3592 818 46 00; Email: svsofia@mbal-sofia.com
    • Principal Investigator: Marchela Koleva, Dr.
  • Sofia, Bulgaria, 1303
    • Active, not recruiting
    • Research Site
  • Sofia, Bulgaria, 1431
    • Active, not recruiting
    • Research Site
  • Sofia, Bulgaria, 1527
    • Active, not recruiting
    • Research Site
  • Sofia, Bulgaria, 1756
    • Active, not recruiting
    • Research Site
  • Stara Zagora, Bulgaria, 6003
    • Not yet recruiting
    • Research Site
    • Contact: Phone Number: +35942614196; Email: oncosz@abv.bg
    • Principal Investigator: Bozhidara Kostova, Dr.
  • Varna, Bulgaria, 9003
    • Active, not recruiting
    • Research Site
  • Pazardzhik
    • Panagyurishte, Pazardzhik, Bulgaria, 4500
      • Not yet recruiting
      • Research Site
      • Contact: Phone Number: +359884 296 946; Email: uni@unihospitalbg.bg
      • Principal Investigator: Rossitza Krasteva, Dr.
• Slovenia
  • Ljubljana, Slovenia, 1000
    • Recruiting
    • Research Site
    • Principal Investigator: Principal Investigator
    • Contact: Email: info@onko-i.si
  • Maribor, Slovenia, 2000
    • Recruiting
    • Research Site
    • Principal Investigator: Principal Investigator
    • Contact: Email: pisarna@ukc-mb.si

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Study Population:

Criteria:

Age: Adult patients (≥18 years). Diagnosis: Confirmed diagnosis of unresectable or metastatic breast cancer (mBC).

HER2 Status: Documented HER2-low status. Treatment Decision: Patients for whom the decision to initiate trastuzumab deruxtecan (T-DXd) treatment has been made independently and prior to enrolment in the study.

Enrollment:

Timing: Patients must be enrolled within 30 days before the administration of the first T-DXd infusion.

Consent: Patients must provide written informed consent for data collection.

Description

Inclusion Criteria:

• Adult patient (age ≥18 years) with histological or cytological confirmed diagnosis of unresectable or mBC.
• Documented HER2-low status (IHC1+, IHC2+/ISH-) in patients who have received prior chemotherapy in the metastatic setting or documented HER2-low status (IHC 1+, IHC 2+/ISH-) in patients who have developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.
• Recent prior decision to initiate therapy of T-DXd per SmPC (up to 30 days). Documentation confirming this decision will be required and collected.
• Able and willing to provide informed consent.

Exclusion Criteria:

• Pregnancy or breastfeeding.
• History of other primary malignancies in 2 years prior to unresectable or mBC diagnosis.
• Patients who at time of data collection for this study are participating in or have participated in an interventional study that remains blinded.
• HER2-low status patients who have previously documented HER2+ status in the same tumor.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Real-world Time to Next Treatment (rwTTNT1, median, 95% CI, measured in months)	The duration from initiation of trastuzumab deruxtecan (T-DXd) treatment to the start of the subsequent therapy or death from any cause, whichever occurs first, assessed up to 19 months.	Baseline up to 19 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Describe type and proportion of previous treatments for unresectable or mBC and comorbidities	Prior treatments: surgery, chemotherapy, radiotherapy, therapies in neoadjuvant/adjuvant/advanced setting; treatment line (special focus should be given on endocrine and chemotherapy recycling in the metastatic setting). The timeline for these treatments will include all therapies administered from the time of breast cancer diagnosis.	Baseline
Duration of previous treatments and number of treatment lines	Start and stop date, if available	Baseline
Response to previous treatments	To describe patients' response to previous treatment, as applicable: clinical response (partial response/complete response/stable disease/disease progression; if progression: date and site of progression)	Baseline
Mean (SD) age at diagnosis	Describe the patients' mean (SD) age at diagnosis	Baseline
Mean (SD) age at T-DXd start	To describe patients' mean (SD) age at T-DXd start	Baseline
Proportion of males and females	To describe the proportion of males and females	Baseline
Proportion of patients with HR+ vs HR- tumors	Describe the proportion of patients with HR+ vs HR- tumors	Baseline
Distribution by smoking status	Describe the patients' smoking status. Includes electronic cigarettes/vapes	Baseline
Type and proportion of comorbidities	Comorbidities (including cardiovascular diseases, pulmonary disorders, hepatic disorders, renal disorders, blood and lymphatic system disorders, metabolism and nutrition disorders, gastrointestinal disorders, hepatobiliary disorders, central nervous system [CNS] disorders, eye disorders, skin disorders and musculoskeletal and connective tissue disorders, infections and infestations and other relevant	Baseline
Distribution by ECOG status	Describe patients' ECOG PS at index date	Baseline
mean (SD) duration of disease (at index), measured in months or years	Describe patients' mean duration of disease through date of initial diagnosis and date of diagnosis of unresectable or metastatic breast cancer, as applicable	Baseline
HER2-low status and type and proportion of metastatic sites	Describe patients' HER2-low status and type and proportion of metastatic sites through most recent HER2-low status, new metastatic sites since the time of mBC diagnosis, disease burden (all disease sites, including the presence/absence of brain metastases [stable/active]	Baseline
rwTTNT1 by Number of Prior of Therapy Lines for Metastatic Disease (median, 95% CI, measured in months, 1 vs 2 vs 3+ Lines)	Describe rwTTNT1 stratified by the number of prior therapy lines in the metastatic setting.	Baseline up to 19 months
rwTTNT1 by HR-status (median, 95% CI, measured in months, HR+ vs HR-)	Describe rwTTNT1 stratified by hormone receptor (HR) status.	Baseline up to 19 months
Real-world Time to Treatment Discontinuation (rwTTD1, median, 95% CI, measured in months)	Evaluate the duration from the start of T-DXd treatment until its discontinuation or death, whichever occurs first.	Baseline up to 19 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Real-world Progression-Free Survival (rwPFS1, median, 95% CI, measured in months)	Evaluate the duration from the start of T-DXd treatment until disease progression or death, whichever occurs first.	Baseline up to 19 months
Real-world Time to Second Next Treatment (rwTTNT2, median, 95% CI, in months)		Baseline up to 19 months
Real-world Time to Subsequent Treatment Discontinuation (rwTTD2, median, 95% CI, measured in months)		Baseline up to 19 months
Real-world progression free survival 2 (rwPFS2, median, 95% CI, measured in months)		Baseline up to 19 months
Biopsy Patterns (number of biopsies conducted prior to the start of T-DXd treatment)	Describe the number of biopsies conducted prior to the start of T-DXd treatment.	Baseline, assessed for the past 10 years
Biopsy Patterns (the time from the last fresh biopsy to the start of T-DXd treatment, measured in months or years)	Describe the time from the last fresh biopsy to the start of T-DXd treatment.	Baseline, assessed for the past 10 years
Reasons for Discontinuation (rwTTNT1 and rwTTNT2)	Evaluate the reasons for discontinuation of T-DXd treatment and subsequent therapy due to disease progression, adverse events, or other reasons.	Baseline up to 19 months
T-DXd Treatment Changes Over Time	Proportion of patients with dose changes, proportion of patients with dose reductions, interruption(s), or treatment discontinuation	Baseline up to 19 months

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2025
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: November 20, 2024
• First Submitted That Met QC Criteria: December 6, 2024
• First Posted (Actual): December 10, 2024

Study Record Updates

• Last Update Posted (Estimated): July 1, 2025
• Last Update Submitted That Met QC Criteria: June 30, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Immunoconjugates; Trastuzumab; Trastuzumab deruxtecan
• Other Study ID Numbers: D9673R00055

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (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
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org.

Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No