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)
Zusammenfassung der Studie
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)
Untersuchte Intervention
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)
Untersuchte Krankheit(en)
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)
Ausschlusskriterien
• 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)
Studienstandort
Basel, Bern, Andere
(BASEC)
Rennaz (Hopital Riviera-Chablais Vaud Valais): closed Frauenfeld (Spital Thurgau AG) Genolier (Hopital de Genolier)
(BASEC)
Sponsor
AstraZeneca AG
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Clinical Trials Schweiz
+41 41 725 75 75
clinical-trials@clutterastrazeneca.comAstraZeneca AG
(BASEC)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Nordwest- und Zentralschweiz EKNZ
(BASEC)
Datum der Bewilligung durch die Ethikkommission
18.01.2024
(BASEC)
ICTRP Studien-ID
NCT06112379 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
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)
Wissenschaftlicher Titel
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)
Öffentlicher Titel
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)
Untersuchte Krankheit(en)
Breast Cancer (ICTRP)
Untersuchte Intervention
Drug: Dato-DXdDrug: DurvalumabDrug: PembrolizumabDrug: DoxorubicinDrug: EpirubicinDrug: CyclophosphamideDrug: PaclitaxelDrug: CarboplatinDrug: CapecitabineDrug: Olaparib (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Ein-/Ausschlusskriterien
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)
nicht verfügbar
Primäre und sekundäre Endpunkte
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)
Registrierungsdatum
12.10.2023 (ICTRP)
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
Daiichi Sankyo (ICTRP)
Weitere Kontakte
AstraZeneca Clinical Study Information Center, information.center@astrazeneca.com, 1-877-240-9479 (ICTRP)
Sekundäre IDs
2023-505928-59-00, D926QC00001 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT06112379 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar