NeoadjuVAnt muLti-agENT Chemotherapy or Patritumab Deruxtecan With or Without endocrINE Therapy for High-risk HR+/HER2- Breast Cancer - VALENTINE Trial

NCT05569811 | Active Not Recruiting Phase 2

• 2 other identifiers: SOLTI-21032022-001181-36
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 25

Brief Summary

VALENTINE is a parallel, non-comparative, three-arm, randomized 1:2:2 open-label, multicenter, exploratory study in women or men with primary operable HR+/HER2-negative breast cancer with ki67 ≥ 20% and/or high genomic risk (defined by gene signature) aiming at evaluating the clinical benefit and biological effects of HER3-DXd with/without letrozole as a neoadjuvant treatment regimen. The primary aim is to evaluate the ability of each treatment strategy to achieve a pCR at surgery. This study is exploratory and no formal comparison between treatment arms is intended. The inclusion of a chemotherapy treatment arm serves as an internal response control instead of using historical data as comparators. In addition, the chemotherapy control arm is the standard of care appropriate treatment in these patients, to include this arm will ensure the recruitment of the target patient population (patients should have indication for neoadjuvant chemotherapy) and allowing comparison of secondary endpoint such as safety and/or HrQoL.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Rate of pCRBL (ypT0/is ypN0) at surgery

  complete absence of invasive carcinoma in the breast and axillary lymph nodes on histological examination.

  before treatment and surgery

Secondary Outcomes (10)

• Rate of Residual cancer burden (RCB) category status (0, I, II, III)

  before treatment and surgery

• pCRB (pathological complete response in the breast)

  before treatment and surgery

• Tumor overall objective response rate (ORR)

  before treatment and pre-surgery

• iDFS rate

  3 years follow-up and 5 years follow-up

• CelTIL score changes

  from baseline to C2D1

Study Arms (3)

CHEMOTHERAPY

ACTIVE COMPARATOR

Drug: Chemotherapy

HER3-DXd + Endocrine therapy (ET)

EXPERIMENTAL

Drug: Patritumab deruxtecan; Drug: Letrozole

HER3-DXd

EXPERIMENTAL

Drug: Patritumab deruxtecan

Interventions

Patritumab deruxtecan DRUG

HER3-DXd will be administered as Lyo-DP, a sterile lyophilized powder in a dose of 5.6 mg/kg

HER3-DXd; HER3-DXd + Endocrine therapy (ET)

Chemotherapy DRUG

Anthracycline/taxane-based neoadjuvant regimen recommended by the NCCN or local guidelines. i.e. EC or AC (epirubicin 90 mg/m2 or doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 14 or 21 days) followed by weekly paclitaxel 80mg/m2 during 12 weeks

CHEMOTHERAPY

Letrozole DRUG

Letrozole and LHRH will be used following SmPC specifications, according to standard therapy and clinical studies

HER3-DXd + Endocrine therapy (ET)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast untreated and recently diagnosed
• ER-positive and/or PgR-positive and HER2-negative tumor
• Ki67% ≥ 20% locally assessed and/or high genomic risk (defined by gene signature):
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Breast cancer eligible for primary surgery.
• Availability of pre-treatment tumor tissue sample of FFPE tumor block from primary tumor for biomarker analysis.
• Participants must be deemed eligible for neoadjuvant chemotherapy
• Participants must be deemed eligible for surgery.
• Adequate hematologic and end-organ function, defined by the following laboratory results
• Baseline LVEF ≥ 50% measured by echocardiography (ECHO) or Multiple Gate Acquisition (MUGA) scan

You may not qualify if:

• Metastatic (Stage IV) breast cancer.
• Bilateral invasive breast cancer.
• Any treatment, local or systemic, including prior chemotherapy, ET, targeted therapy, and/or radiation therapy for the currently diagnosed BC prior to enrollment.
• Patients in whom a primary tumor excisional biopsy was performed.
• Prior treatment with a HER3 antibody, topoisomerase I inhibitor, with an ADC which consists of an exatecan derivative that is a topoisomerase I inhibitor (e.g., DS-8201) and with a govitecan derivative (e.g., IMMU-132).
• Patient has active cardiac disease or a history of cardiac dysfunction.
• Medical history of clinically significant lung diseases (e.g., interstitial pneumonia, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis) or who are suspected to have these diseases by imaging at screening period.
• Patients with a history of any malignancy are ineligible except specific cases
• Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary or metabolic disease; wound healing disorders; ulcers; bone fractures, psychiatric illness/social situations, geographical factors, substance abuse) or other factors which in the Investigator's opinion makes it undesirable for the subject to participate in the study or which would jeopardize compliance with the protocol
• Concurrent, serious, uncontrolled infections or current known infection with HIV or active hepatitis B and/or hepatitis C.
• History of significant co-morbidities that, in the judgment of the investigator, may interfere with the conduction of the study, the evaluation of response, or with ICF.
• Known hypersensitivity to either the drug substance components (including an antibody, a drug-linker, or a topoisomerase I inhibitor) or inactive ingredients in the drug product or history of severe hypersensitivity reactions to other monoclonal antibodies.
• History of exposure to cumulative anthracycline doses greater than follows: a. Adriamycin \> 100 mg/m2; Epirubicin \> 180 mg/m2; Mitoxantrone \> 40 mg/m2; Idarubicin \> 22.5 mg/m2. If another anthracycline or more than one anthracycline has been used, the cumulative dose must not exceed the equivalent of 100 mg/m2 of adriamycin.
• Any history of interstitial lung disease (ILD) (including pulmonary fibrosis or radiation pneumonitis), has current ILD, or is suspected to have such disease by imaging during screening.
• Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e. pulmonary emboli within three months of the study enrollment, severe asthma, severe COPD, restrictive lung disease, pleural effusion etc.), and any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement (i.e. rheumatoid arthritis, Sjögren's syndrome, sarcoidosis etc.), or prior pneumonectomy.

Sponsors & Collaborators

• SOLTI Breast Cancer Research Group: lead
• Daiichi Sankyo: collaborator

Study Sites (25)

ICO Badalona

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitario de Canarias

Santa Cruz de Tenerife, Canary Islands, 38320, Spain

Location

Complejo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, La Coruña, 15006, Spain

Location

Hospital Universitario de Fuenlabrada

Fuenlabrada, Madrid, Spain

Location

Hospital Universitario Rey Juan Carlos

Móstoles, Madrid, 28933, Spain

Location

Hospital Universitario de Badajoz

Badajoz, 06080, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital General de Catalunya

Barcelona, Spain

Location

Hospital Universitari Vall d' Hebrón

Barcelona, Spain

Location

Hospital de Basurto

Bilbao, Spain

Location

Complejo Hospitalario San Pedro de Alcántara

Cáceres, 10003, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

Location

Hospital Universitario Virgen de las Nieves

Granada, 18014, Spain

Location

H.Univ. Arnau de Vilanova de Lleida

Lleida, Spain

Location

Hospital Universitario Puerta de Hierro de Majadahonda

Madrid, 28222, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

HAU de Manresa

Manresa, Spain

Location

Hospital Universitario Virgen de la Arrixaca

Murcia, 30120, Spain

Location

Hospital Son Espases

Palma de Mallorca, Spain

Location

Hospital Sant Joan de Reus

Reus, 43204, Spain

Location

HU Parc Tauli

Sabadell, Spain

Location

Comp. Hosp.Univ. Santiago (Chus)

Santiago de Compostela, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, Spain

Location

H La Fe

Valencia, Spain

Location

Hospital Clínico de Valencia

Valencia, Spain

Location

Related Links

• Related Info

MeSH Terms

Conditions

Breast Neoplasms

Interventions

patritumab deruxtecan; Drug Therapy; Letrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

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

Study Record Dates

• First Submitted: September 27, 2022
• First Posted: October 6, 2022
• Study Start: November 25, 2022
• Primary Completion: March 31, 2025
• Study Completion (Estimated): July 31, 2030
• Last Updated: September 21, 2023

Record last verified: 2023-09

Locations

ES (25)