Trial Title:
NeoadjuVAnt muLti-agENT Chemotherapy or Patritumab Deruxtecan With or Without endocrINE Therapy for High-risk HR+/HER2- Breast Cancer - VALENTINE Trial
NCT ID:
NCT05569811
Condition:
Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Letrozole
Patritumab deruxtecan
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Patritumab deruxtecan
Description:
HER3-DXd will be administered as Lyo-DP, a sterile lyophilized powder in a dose of 5.6
mg/kg
Arm group label:
HER3-DXd
Arm group label:
HER3-DXd + Endocrine therapy (ET)
Intervention type:
Drug
Intervention name:
Chemotherapy
Description:
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
Arm group label:
CHEMOTHERAPY
Intervention type:
Drug
Intervention name:
Letrozole
Description:
Letrozole and LHRH will be used following SmPC specifications, according to standard
therapy and clinical studies
Arm group label:
HER3-DXd + Endocrine therapy (ET)
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.
Criteria for eligibility:
Criteria:
Main inclusion criteria
1. Histologically confirmed non-metastatic primary invasive adenocarcinoma of the
breast untreated and recently diagnosed
2. ER-positive and/or PgR-positive and HER2-negative tumor
3. Ki67% ≥ 20% locally assessed and/or high genomic risk (defined by gene signature):
4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
5. Breast cancer eligible for primary surgery.
6. Availability of pre-treatment tumor tissue sample of FFPE tumor block from primary
tumor for biomarker analysis.
7. Participants must be deemed eligible for neoadjuvant chemotherapy
8. Participants must be deemed eligible for surgery.
9. Adequate hematologic and end-organ function, defined by the following laboratory
results
10. Baseline LVEF ≥ 50% measured by echocardiography (ECHO) or Multiple Gate Acquisition
(MUGA) scan
Main exclusion criteria
1. Metastatic (Stage IV) breast cancer.
2. Bilateral invasive breast cancer.
3. Any treatment, local or systemic, including prior chemotherapy, ET, targeted
therapy, and/or radiation therapy for the currently diagnosed BC prior to
enrollment.
4. Patients in whom a primary tumor excisional biopsy was performed.
5. 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).
6. Patient has active cardiac disease or a history of cardiac dysfunction.
7. 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.
8. Patients with a history of any malignancy are ineligible except specific cases
9. 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
10. Concurrent, serious, uncontrolled infections or current known infection with HIV or
active hepatitis B and/or hepatitis C.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. Has unresolved toxicities from previous anticancer therapy, defined as toxicities
(other than alopecia) not yet resolved to National Cancer Institute Common
Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, grade ≤1 or
baseline. Subjects with chronic grade 2 toxicities may be eligible per the
discretion of the Investigator.
17. Non-eligible for taxanes therapy. Previous sensory neuropathy > grade 1, according
to NCI-CTCAE criteria, due to any reason.
18. Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or
equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior
to Cycle 1 Day 1. Subjects who require use of bronchodilators, inhaled or topical
steroids, or local steroid injections may be included in the study.
19. Evidence of any leptomeningeal disease.
20. Has clinically significant corneal disease.
21. Female subject who is pregnant or breastfeeding or intends to become pregnant during
the study.
22. Subjects who are currently receiving chloroquine or hydroxychloroquine. A washout
period of > 14 days is required prior to randomization or Cycle 1 Day 1
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
ICO Badalona
Address:
City:
Badalona
Zip:
08916
Country:
Spain
Facility:
Name:
Hospital Universitario de Canarias
Address:
City:
Tenerife
Zip:
38320
Country:
Spain
Facility:
Name:
Complejo Hospitalario Universitario A Coruña (CHUAC)
Address:
City:
A Coruña
Zip:
15006
Country:
Spain
Facility:
Name:
Hospital Universitario de Fuenlabrada
Address:
City:
Fuenlabrada
Country:
Spain
Facility:
Name:
Hospital Universitario Rey Juan Carlos
Address:
City:
Móstoles
Zip:
28933
Country:
Spain
Facility:
Name:
Hospital Universitario de Badajoz
Address:
City:
Badajoz
Zip:
06080
Country:
Spain
Facility:
Name:
Hospital Clinic de Barcelona
Address:
City:
Barcelona
Zip:
08036
Country:
Spain
Facility:
Name:
Hospital General de Catalunya
Address:
City:
Barcelona
Country:
Spain
Facility:
Name:
Hospital Universitari Vall d' Hebrón
Address:
City:
Barcelona
Country:
Spain
Facility:
Name:
Hospital de Basurto
Address:
City:
Bilbao
Country:
Spain
Facility:
Name:
Complejo Hospitalario San Pedro de Alcántara
Address:
City:
Cáceres
Zip:
10003
Country:
Spain
Facility:
Name:
Hospital Universitario Reina Sofia
Address:
City:
Córdoba
Zip:
14004
Country:
Spain
Facility:
Name:
Hospital Universitario Virgen de las Nieves
Address:
City:
Granada
Zip:
18014
Country:
Spain
Facility:
Name:
H.Univ. Arnau de Vilanova de Lleida
Address:
City:
Lleida
Country:
Spain
Facility:
Name:
Hospital Universitario Puerta de Hierro de Majadahonda
Address:
City:
Madrid
Zip:
28222
Country:
Spain
Facility:
Name:
Hospital Universitario 12 de Octubre
Address:
City:
Madrid
Country:
Spain
Facility:
Name:
HAU de Manresa
Address:
City:
Manresa
Country:
Spain
Facility:
Name:
Hospital Universitario Virgen de la Arrixaca
Address:
City:
Murcia
Zip:
30120
Country:
Spain
Facility:
Name:
Hospital Son Espases
Address:
City:
Palma De Mallorca
Country:
Spain
Facility:
Name:
Hospital Sant Joan de Reus
Address:
City:
Reus
Zip:
43204
Country:
Spain
Facility:
Name:
HU Parc Tauli
Address:
City:
Sabadell
Country:
Spain
Facility:
Name:
Comp. Hosp.Univ. Santiago (Chus)
Address:
City:
Santiago De Compostela
Country:
Spain
Facility:
Name:
Hospital Universitario Virgen del Rocio
Address:
City:
Sevilla
Country:
Spain
Facility:
Name:
H La Fe
Address:
City:
Valencia
Country:
Spain
Facility:
Name:
Hospital Clínico de Valencia
Address:
City:
Valencia
Country:
Spain
Start date:
November 25, 2022
Completion date:
July 31, 2030
Lead sponsor:
Agency:
SOLTI Breast Cancer Research Group
Agency class:
Other
Collaborator:
Agency:
Daiichi Sankyo
Agency class:
Industry
Source:
SOLTI Breast Cancer Research Group
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05569811
https://www.gruposolti.org/
