DS-8201a for trEatment of aBc, BRain Mets, And Her2[+] Disease

NCT04420598 | Completed Phase 2 Results

• 2 other identifiers: MEDOPP2432019-001739-29
• Study Type: interventional
• Target: 41
• Locations: 2 countries
• Sites: 16

Brief Summary

This is a multicenter, international, open-label, single-arm, multicohort, two-stage optimal Simon's design, phase II clinical trial

Conditions

Advanced Breast Cancer; HER2-positive Breast Cancer; Brain Metastases; Leptomeningeal Metastasis

Keywords

Breast cancer; HER2; Brain metastases; Metastatic; unresectable; pretreated

Outcome Measures

Primary Outcomes (3)

• 16 Weeks PFS Per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) (Cohort 1)

  This outcome measure evaluates progression-free survival (PFS) in Cohort 1 over a 16-week period, using the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria.

  From baseline up to 16 weeks

• Objective Response Rate According RANO-BM (Cohorts 2, 3 and 4)

  The proportion of patients achieving either Complete Response (CR) or Partial Response (PR) at any assessment time point, based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria

  Each participant was assessed from baseline until the last tumor response evaluation, up to 16 months.

• Overall Survival in Cohort 5

  Median of OS rate for patients

  Each participant was assessed from baseline until the last tumor response evaluation, up to 16 months.

Secondary Outcomes (4)

• Intra-cranial Evaluation According to RANO-BM

  Each participant was assessed from baseline until the last tumor response evaluation, up to 16 months.

• Extra-cranial Evaluation According to RECIST v1.1

  Each participant was assessed from baseline until the last tumor response evaluation, up to 16 months.

• Global Evaluation According to RECIST v1.1

  Each participant was assessed from baseline until the last tumor response evaluation, up to 16 months.

• Unconfirmed Clinical Benefit Rate According to RANO-BM and RECIST v1.1

  Each participant was assessed from baseline until the last tumor response evaluation, up to 16 months.

Study Arms (1)

Trastuzumab deruxtecan (DS-8201a)

EXPERIMENTAL

* Cohort 1: HER2-positive BC with non-progressing BM (after WBRT and/or SRS and or surgery.); * Cohort 2: HER2-positive or HER2-low BC with asymptomatic untreated BM; * Cohort 3: HER2-positive BC with progressing BMs after local treatment; * Cohort 4: HER2-low expressing BC with progressing BMs after local treatment; * Cohort 5: HER2-positive or HER2-low expressing BC with LMC.

Drug: Trastuzumab deruxtecan

Interventions

Trastuzumab deruxtecan DRUG

After having confirmed eligibility and entered into the clinical trial, patients will be treated with trastuzumab deruxtecan (DS-8201a) at 5.4 mg/Kg administered as an intravenous (IV) infusion on Day of 21-day cycle (Q3W), initially for at least 90 minutes, then, if there is no infusion-related reaction, for a minimum of 30 minutes. In patients with hormone receptor (HR)-positive status (estrogen receptor \[ER\] and/or progesterone receptor \[PgR\]) administration of endocrine therapy is not allowed. In patients allocated in study cohort 5, administration of intrathecal therapy is not allowed

Also known as: (DS-8201a)

Trastuzumab deruxtecan (DS-8201a)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent Form (ICF) prior to participation in any study-related activities.
• Male or female patients ≥ 18 years at the time of signing ICF.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 for Cohorts 1 to 4 and 0-2 for cohort 5.
• Life expectancy ≥ 12 weeks.
• Histologically confirmed invasive breast cancer based on local testing on the most recent analyzed biopsy of the following breast cancer (BC) subtypes per 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) criteria:
• Cohort 1 and 3: HER2 positive status
• Cohort 4: HER2-low expressing status
• Cohort 2 and 5: both HER2 positive and HER2-low expressing status
• Note 1: According to the 2018 ASCO-CAP guidelines, HER2- positive status is defined as HER2 immunohistochemistry (IHC) 3+, in situ hybridization (ISH) ≥ 2.0, or average HER2 copy number ≥ 6.0 signals. HER2-low expressing status defined as IHC 2+ / ISH-negative or IHC 1+ (ISH-negative or untested).
• Note 2: Central confirmation of HER2 is not required for study entry. However, tissue blocks, or slides, must be submitted to confirm BC subtype by a Sponsor-designated central laboratory retrospectively.
• Unresectable locally advanced or metastatic disease documented by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to resection with curative intent.
• At least one brain lesion needed to be measurable (≥10 mm on T1-weighted, gadolinium-enhanced MRI) (study cohorts 2 to 4) or leptomeningeal carcinomatosis (LMC) with positive cerebrospinal fluid (CSF) cytology (study cohort 5).
• Study cohort 1: History of BM that are non-progressing after WBRT and/or SRS and or surgery.
• Study cohort 2: Presence of asymptomatic BM without clinical requirement for local intervention (WBRT and/or SRS and/or surgery).
• Study cohorts 3 and 4: Evidence of new and/or progressive BM following previous WBRT and/or SRS and/or surgery.

You may not qualify if:

• Patients will be excluded from the study if they meet ANY of the following criteria:
• Inability to comply with study and follow-up procedures.
• Previous treatment with trastuzumab deruxtecan (DS-8201a) or any other antibody drug conjugate (ADC) which consists of an exatecan derivative that is a topoisomerase 1 inhibitor.
• Medical history of myocardial infarction within 6 months before enrollment, symptomatic congestive heart failure (New York Heart Association Class II to IV), troponin levels consistent with myocardial infarction within 28 days prior to enrollment.
• Corrected QT interval (QTc) prolongation to \> 470 ms (females) or \>450 ms (males) based on average of the screening triplicate12- lead ECG.
• History of (non-infectious) interstitial lung disease (ILD) that required steroids, has current ILD, or where suspected ILD cannot be ruled out by imaging at screening.
• Clinically significant corneal disease in the opinion of the Investigator.
• Spinal cord compression.
• Multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, other solid tumors curatively treated, or contralateral breast cancer.
• History of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product.
• History of severe hypersensitivity reactions to other monoclonal antibodies.
• Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
• Patients with substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results.
• Known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection. Subjects should be tested for HIV prior to enrollment if required by local regulations or institutional review board (IRB)/ethics committee (EC).
• Female patients who are pregnant or breastfeeding or planning to become pregnant.

Sponsors & Collaborators

• MedSIR: lead
• Daiichi Sankyo: collaborator

Study Sites (16)

Champalimaud Center for the Unknown

Lisbon, Portugal

Location

Instituto Português de Oncologia do Porto Francisco Gentil, EPE (IPO Porto)

Porto, Portugal

Location

Institut Català d'Oncologica ICO Badalona

Badalona, Spain

Location

Hospital Universitari Dexeus

Barcelona, 08028, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

Institut Oncologic Baselga-Hospital Quiron Salud Barcelona

Barcelona, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, Spain

Location

Institut Catala d'Oncologia ICO Hospitalet

L'Hospitalet de Llobregat, Spain

Location

Hospital Clínico San Carlos

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, Spain

Location

IOB- Complejo Hospitalario Ruber Juan Bravo

Madrid, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, Spain

Location

Fundación Instituto Valenciano de Oncología (IVO)

Valencia, 46009, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, Spain

Location

Hospital Universitario Migue Servet

Zaragoza, Spain

Location

Related Publications (2)

• Vaz Batista M, Perez-Garcia JM, Garrigos L, Garcia-Saenz JA, Cortez P, Racca F, Blanch S, Ruiz-Borrego M, Fernandez-Ortega A, Fernandez-Abad M, Iranzo V, Gion M, Martrat G, Alcala-Lopez D, Perez-Escuredo J, Sampayo-Cordero M, Llombart-Cussac A, Braga S, Cortes J. The DEBBRAH trial: Trastuzumab deruxtecan in HER2-positive and HER2-low breast cancer patients with leptomeningeal carcinomatosis. Med. 2025 Jan 10;6(1):100502. doi: 10.1016/j.medj.2024.08.001. Epub 2024 Sep 11.

  PMID: 39265579 DERIVED

• Vaz Batista M, Perez-Garcia JM, Cortez P, Garrigos L, Fernandez-Abad M, Gion M, Martinez-Bueno A, Saavedra C, Teruel I, Fernandez-Ortega A, Servitja S, Ruiz-Borrego M, de la Haba-Rodriguez J, Martrat G, Perez-Escuredo J, Alcala-Lopez D, Sampayo-Cordero M, Braga S, Cortes J, Llombart-Cussac A. Trastuzumab deruxtecan in patients with previously treated HER2-low advanced breast cancer and active brain metastases: the DEBBRAH trial. ESMO Open. 2024 Sep;9(9):103699. doi: 10.1016/j.esmoop.2024.103699. Epub 2024 Sep 9.

  PMID: 39255534 DERIVED

MeSH Terms

Conditions

Brain Neoplasms; Meningeal Carcinomatosis; Breast Neoplasms; Neoplasm Metastasis

Interventions

trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Meningeal Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Alicia García Sanz PhD
• Organization: Medica Scientia Innovation Research (Medsir)

contact.trials@medsir.org

611261467

Study Officials

• Marta Vaz Batista, MD

  MedSIR

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a multicenter, international, open-label, single-arm, multicohort, two-stage optimal Simon's design, phase II clinical trial. After confirmed eligibility, patients will be assigned to one of the following five study cohorts: * Cohort 1: HER2-positive BC with non-progressing BM (after WBRT and/or SRS and or surgery.); * Cohort 2: HER2-positive or HER2-low BC with asymptomatic untreated BM; * Cohort 3: HER2-positive BC with progressing BMs after local treatment; * Cohort 4: HER2-low expressing BC with progressing BMs after local treatment; * Cohort 5: HER2-positive or HER2-low expressing BC with LMC

Study Record Dates

• First Submitted: May 25, 2020
• First Posted: June 9, 2020
• Study Start: May 25, 2020
• Primary Completion: September 30, 2021
• Study Completion: April 4, 2023
• Last Updated: June 24, 2025
• Results First Posted: June 24, 2025

Record last verified: 2025-06

Locations

PT (2); ES (14)