Study with Datopotamab Deruxtecan (Dato-DXd) plus Durvalumab before surgery followed by Durvalumab with or without chemotherapy after surgery compared to Pembrolizumab plus chemotherapy before surgery followed by Pembrolizumab with or without chemotherapy after surgery for the treatment of adult patients with previously untreated triple-negative or hormone receptor-low/HER2-negative breast cancer (D926QC00001; TROPION-Breast04)
Résumé de l'étude
This study will examine an investigational substance, Datopotamab Deruxtecan (Dato-DXd), in combination with Durvalumab in previously untreated triple-negative or hormone receptor-low/HER2-negative breast cancer. The aim is to determine how effective (for example, by reducing the growth or spread of breast cancer) and safe Datopotamab Deruxtecan is when administered in combination with Durvalumab. This combination therapy will be compared to a standard treatment for this type of breast cancer (Pembrolizumab plus chemotherapy). Each chemotherapy will be selected by the investigator (from a selection of Doxorubicin/Epirubicin, Cyclophosphamide, Paclitaxel, Carboplatin, or Capecitabine or a combination of these), depending on the type of breast cancer and how the cancer responded to the treatment given before surgery. If the breast cancer has a certain type of mutation (the so-called BRCA mutation) and if cancer cells are still found at the time of surgery, Olaparib may also be administered.
(BASEC)
Intervention étudiée
All participants will be randomly assigned in a 1:1 ratio to the following groups:
A) Dato-DXd and Durvalumab as neoadjuvant therapy (before surgery), administered intravenously every 3 weeks over a period of 24 weeks. After surgery (adjuvant therapy), Durvalumab will be administered every 3 weeks for an additional 24 weeks.
B) Neoadjuvant therapy: Pembrolizumab together with Carboplatin and Paclitaxel administered intravenously weekly over a period of 12 weeks. Then every 3 weeks Pembrolizumab and Cyclophosphamide plus either Doxorubicin or Epirubicin for an additional 12 weeks before surgery. After surgery, Pembrolizumab will be administered alone for an additional 27 weeks.
If cancer cells are still detected after surgery, chemotherapy may be combined. If the tumor has a BRCA mutation, Olaparib (tablet, oral) may be administered for 1 year, but not simultaneously with chemotherapy.
(BASEC)
Maladie en cours d'investigation
Untreated triple-negative or hormone receptor-low/HER2-negative breast cancer (TNBC)
(BASEC)
• Male and female patients (≥18 years) with a histologically confirmed previously untreated triple-negative or hormone receptor-low/HER2-negative breast cancer, with an available tumor sample • ECOG performance status 0-1 • Adequate organ and bone marrow function (BASEC)
Critères d'exclusion
• Clinically significant corneal disease, severe impairment of lung function or uncontrolled infection, heart disease, immune disorders, systemic diseases • Previous surgery, radiation, systemic therapy for TNBC/HR-2-low breast cancer • No metastases; no previous cancer within 3 years prior to inclusion. Exceptions: resected skin cancer that is not melanoma, as well as curatively treated in-situ carcinoma (precursor to cancer) (BASEC)
Lieu de l’étude
Bâle, Berne, Autre
(BASEC)
Rennaz (Hopital Riviera-Chablais Vaud Valais): closed Frauenfeld (Spital Thurgau AG) Genolier (Hopital de Genolier)
(BASEC)
Sponsor
AstraZeneca AG
(BASEC)
Contact pour plus d'informations sur l'étude
Personne de contact en Suisse
Clinical Trials Schweiz
+41 41 725 75 75
clinical-trials@clutterastrazeneca.comAstraZeneca AG
(BASEC)
Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)
Ethikkommission Nordwest- und Zentralschweiz EKNZ
(BASEC)
Date d'approbation du comité d'éthique
18.01.2024
(BASEC)
Identifiant de l'essai ICTRP
NCT06112379 (ICTRP)
Titre officiel (approuvé par le comité d'éthique)
A Phase III, Open-label, Randomised Study of Neoadjuvant Datopotamab Deruxtecan (Dato DXd) Plus Durvalumab Followed by Adjuvant Durvalumab with or Without Chemotherapy Versus Neoadjuvant Pembrolizumab Plus Chemotherapy Followed by Adjuvant Pembrolizumab With or Without Chemotherapy for the Treatment of Adult Patients with Untreated Triple-Negative or Hormone Receptor low/HER2-negative Breast Cancer (D926QC00001; TROPION Breast04) (BASEC)
Titre académique
A Phase III, Open-label, Randomised Study of Neoadjuvant Datopotamab Deruxtecan (Dato-DXd) Plus Durvalumab Followed by Adjuvant Durvalumab With or Without Chemotherapy Versus Neoadjuvant Pembrolizumab Plus Chemotherapy Followed by Adjuvant Pembrolizumab With or Without Chemotherapy for the Treatment of Adult Patients With Previously Untreated Triple-Negative or Hormone Receptor-low/HER2-negative Breast Cancer (D926QC00001 TROPION-Breast04) (ICTRP)
Titre public
A Phase III Randomised Study to Evaluate Dato-DXd and Durvalumab for Neoadjuvant/Adjuvant Treatment of Triple-Negative or Hormone Receptor-low/HER2-negative Breast Cancer (ICTRP)
Maladie en cours d'investigation
Breast Cancer (ICTRP)
Intervention étudiée
Drug: Dato-DXdDrug: DurvalumabDrug: PembrolizumabDrug: DoxorubicinDrug: EpirubicinDrug: CyclophosphamideDrug: PaclitaxelDrug: CarboplatinDrug: CapecitabineDrug: Olaparib (ICTRP)
Type d'essai
Interventional (ICTRP)
Plan de l'étude
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Critères d'inclusion/exclusion
Inclusion Criteria:
- Participant must be = 18 years, at the time of signing the ICF.
- Histologically confirmed Stage II or III unilateral or bilateral primary invasive
TNBC or hormone receptor-low/HER2-negative breast cancer
- ECOG PS of 0 or 1
- Provision of acceptable tumor sample
- Adequate bone marrow reserve and organ function
- Contraceptive use by males or females should be consistent with local regulations
regarding the methods of contraception for those participating in clinical studies
and aligned with protocol requirements.
Exclusion criteria:
- History of any prior invasive breast malignancy
- History of another primary malignancy except for malignancy treated with curative
intent with no known active disease within 5 years before randomization.
- active or prior documented autoimmune or inflammatory disorders.
- Evidence of distant disease.
- Clinically significant corneal disease.
- Has active or uncontrolled hepatitis B or C virus infection.
- Known HIV infection that is not well controlled.
- Uncontrolled infection requiring i.v. antibiotics, antivirals or antifungals
suspected infections or inability to rule out infections.
- Known to have active tuberculosis infection
- Mean resting corrected QTcF interval > 470 ms obtained from ECG
- Uncontrolled or significant cardiac disease.
- History of non-infectious ILD/pneumonitis
- Has severe pulmonary function compromise
- Any prior or concurrent surgery, radiotherapy or systemic anticancer therapy for
TNBC or hormone receptor-low/HER2-negative breast cancer
- For females only: is pregnant (confirmed with positive serum pregnancy test) or
breastfeeding, or planning to become pregnant.
- Female participants should refrain from breastfeeding from enrolment throughout the
study and for at least 7 months after last dose of study intervention, or as
dictated by local PI for SoC if longer.
- Concurrent use of systemic hormone replacement therapy or oral hormonal
contraception (ICTRP)
non disponible
Critères d'évaluation principaux et secondaires
Pathologic Complete Response (pCR) in the experimental vs control arms;Event-free survival (EFS) in the experimental vs control arms (ICTRP)
Overall Survival (OS) in the experimental vs control arms;Distant disease-free survival (DDFS) in the experimental vs control arms;Participant-reported breast and arm symptoms in the experimental vs. control arms;Participant-reported physical function in the experimental vs. control arms;Participant-reported fatigue in the experimental vs. control arms;Participant-reported Global health status/Quality of life (GHS/QoL)in the experimental vs. control arms;Pharmacokinetics of Dato-DXd (in combination with durvalumab);Pharmacokinetics of Dato-DXd (in combination with durvalumab);Pharmacokinetics of Dato-DXd (in combination with durvalumab);Immunogenicity of Dato-DXd (in combination with durvalumab);Safety of Dato-DXd (in combination with durvalumab) (ICTRP)
Date d'enregistrement
12.10.2023 (ICTRP)
Inclusion du premier participant
non disponible
Sponsors secondaires
Daiichi Sankyo (ICTRP)
Contacts supplémentaires
AstraZeneca Clinical Study Information Center, information.center@astrazeneca.com, 1-877-240-9479 (ICTRP)
ID secondaires
2023-505928-59-00, D926QC00001 (ICTRP)
Résultats-Données individuelles des participants
non disponible
Informations complémentaires sur l'essai
https://clinicaltrials.gov/ct2/show/NCT06112379 (ICTRP)
Résultats de l'essai
Résumé des résultats
non disponible
Lien vers les résultats dans le registre primaire
non disponible