CTRI/2024/04/065322Active, not recruitingPhase 3
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)
Trial Snapshot
- Phase
- Phase 3
- Status
- Active, not recruiting
- Sponsor
- AstraZeneca AB
- Enrollment
- 1,728
- Locations
- 12
- Primary Endpoint
- To demonstrate superiority of neoadjuvant Dato DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy relative to neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab with or without chemotherapy in participants with previously untreated TNBC or hormone receptor-low HER2-negative breast cancer, by central assessment of pCR.
Study Overview
Brief Summary
Brief Summary This is a Phase III, 2-arm, randomised, open-label, multicentre, global study assessing the efficacy and safety of neoadjuvant Dato-DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy compared with neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab with or without chemotherapy in participants with previously untreated TNBC or hormone receptor-low/HER2-negative breast cancer. Study details include: • The study duration will be up to 82 months after the first participant has been randomised. • The treatment duration will be approximately 57 weeks (24 weeks of treatment in the neoadjuvant setting followed by surgery 25 days to 6 weeks after conclusion of neoadjuvant treatment or following early discontinuation, then 27 weeks of treatment in the adjuvant setting). Treatment duration will be longer for participants receiving up to 1 year of adjuvant olaparib treatment. Adjuvant radiotherapy may be given concurrently with adjuvant durvalumab or pembrolizumab monotherapy but not concurrently with adjuvant chemotherapy. Adjuvant endocrine therapy for hormone receptor-low tumours is permitted per investigator’s discretion (Note: participants cannot receive adjuvant CDK4/6 inhibitor therapy, including abemaciclib and ribociclib). All participants will receive study intervention in the neoadjuvant and adjuvant setting. Note, endocrine therapy is not considered study intervention and as such will not be provided by AstraZeneca. • The on-treatment visit frequency will be weekly to Q3W.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Masking
- None
Eligibility Criteria
- Ages
- 18.00 Year(s) to 99.00 Year(s) (—)
- Sex
- All
Inclusion Criteria
- •Inclusion criteria Informed consent Age
- •Participant must be 18 years, at the time of signing the ICF.
- •Type of Participant and Disease Characteristics
- •Histologically confirmed Stage II or III unilateral or bilateral primary invasive TNBC or hormone receptor-low/HER2-negative breast cancer defined as the following combined primary tumour T and regional lymph node N staging per AJCC for breast cancer staging system edition 8 as assessed by the investigator based on radiological and/or clinical assessment.
- •Negative for ER with 1 of tumour cells positive for ER on IHC and negative for PR with of tumour cells positive for PR on IHC, or hormone receptor-low and TNBC or hormone receptor-low/HER2-negative breast cancer is defined as:
- •Negative for HER2 with 0 or 1 intensity on IHC, or 2 intensity on IHC and no evidence of amplification on ISH.
- •ECOG PS of 0 or
- •Provision of acceptable tumour sample prior to randomisation as defined in the Laboratory Manual.
- •Note: Sample collected in China will comply with local regulatory approval.
- •Adequate bone marrow reserve and organ function within 7 days before randomisation, Sex and Contraceptive/Barrier Requirements
- •Male and/or female Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •Informed Consent
- •Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this CSP.
- •Provision of signed and dated written optional genetic research information informed consent prior to collection of samples for optional genetic research that supports the Genomic Initiative.
- •Other Inclusion Criteria
- •All races, gender and ethnic groups are eligible for this study.
Exclusion Criteria
- •Exclusion criteria Medical conditions Participants are excluded from the study if any of the following criteria apply: Medical Conditions
- •As judged by the investigator, any evidence of diseases such as severe or uncontrolled systemic diseases, which, in the investigator’s opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol.
- •Refractory nausea and vomiting, inability to swallow a formulated product, or previous significant bowel resection, that would preclude adequate absorption, distribution, metabolism, or excretion of capecitabine or olaparib.
- •History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before randomisation and of low potential risk for recurrence.
- •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.
- •Are HBsAg-positive with chronic HBV infection
- •Known HIV infection that is not well controlled.
- •Uncontrolled infection requiring i.v. antibiotics, antivirals or antifungals; suspected infections.
- •Known to have active tuberculosis infection
- •Resting ECG with clinically significant abnormal findings.
- •History of non-infectious ILD pneumonitis including radiation pneumonitis that required steroids, has current ILD pneumonitis, or has suspected ILD pneumonitis that cannot be ruled out by imaging at screening.
- •Has severe pulmonary function compromise.
- •Prior/Concomitant Therapy
- •Any concomitant medication known to be associated with torsades de pointes.
- •Any prior or concurrent surgery, radiotherapy or systemic anticancer therapy for TNBC or hormone receptor-low/HER2-negative breast cancer.
- •Prior exposure to chloroquine/hydroxychloroquine without an adequate treatment washout period of 14 days before randomisation.
- •Current or prior use of immunosuppressive medication within 14 days before the first dose of study intervention.
- •Receipt of live, attenuated vaccine within 30 days prior to the first dose of study intervention.
Outcomes
Primary Outcomes
To demonstrate superiority of neoadjuvant Dato DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy relative to neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab with or without chemotherapy in participants with previously untreated TNBC or hormone receptor-low HER2-negative breast cancer, by central assessment of pCR.
Time Frame: To demonstrate superiority of neoadjuvant Dato DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy relative to neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab with or without chemotherapy in participants with previously untreated TNBC or hormone receptor-low HER2-negative breast cancer, by central assessment of pCR. | Baseline and 6 Months ( Post surgery) and 18 Months (Completion of adjuvant treatment)
Secondary Outcomes
- To demonstrate superiority of neoadjuvant Dato DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy relative to neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab with or without chemotherapy in participants with previously untreated TNBC or hormone receptor-low/HER2-negative breast cancer, by assessment of OS.(OS is defined as the time from the date of randomisation until the date of death due to any cause.)
- To assess effectiveness of neoadjuvant Dato DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy relative to neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab with or without chemotherapy in participants with previously untreated TNBC or hormone receptor-low HER2-negative breast cancer, by assessment of DDFS.(DDFS is defined as the time from the date of randomisation until the date of the first occurrence of any of the following events: distant metastasis, occurrence of second primary non-breast invasive cancer other than squamous or basal cell skin cancer, or death by any cause (in the absence of recurrence. DDFS will be determined by the investigator based on all available clinical assessments.)
- To assess participant-reported breast and arm symptoms in participants with previously untreated TNBC or hormone receptor-low/HER2-negative breast cancer treated with neoadjuvant Dato DXd plus durvalumab relative to neoadjuvant pembrolizumab plus chemotherapy.(Actual scores at Weeks 12 and 24 of the neoadjuvant period in breast and arm symptoms as measured by the EORTC IL116.)
- To assess participant reported physical function in participants with previously untreated TNBC or hormone receptor-low/HER2-negative breast cancer treated with neoadjuvant Dato DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy relative to neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab with or without chemotherapy.(Actual scores at Weeks 12 and 24 of the neoadjuvant period, and Weeks 12, 27, and Year 1 of the adjuvant period in physical function as measured by the PROMIS Physical Function Short Form 8c.)
- To assess participant reported fatigue in participants with previously untreated TNBC or hormone receptor low/HER2-negative breast cancer treated with neoadjuvant Dato DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy relative to neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab with or without chemotherapy.(Proportion of participants experiencing different levels of fatigue and actual scores at 12 and 24 weeks during the neoadjuvant phase and at 12 and 27 weeks during the adjuvant phase as measured by the PROMIS Fatigue Short Form 7a.)
- To assess participant-reported GHS/QoL in participants with previously untreated TNBC or hormone receptor low/HER2-negative breast cancer treated with neoadjuvant Dato DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy relative to neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab with or without chemotherapy.(Actual scores at Weeks 12 and 24 of the neoadjuvant period, and Weeks 12, 27, and Year 1 of the adjuvant period in GHS/QoL as measured by the GHS/QoL scale from EORTC IL172.)
- To assess the PK of Dato DXd, total anti TROP2 antibody and DXd (in combination with durvalumab).(Plasma concentrations of Dato-DXd, total anti-TROP2 antibody, and DXd.)
- To investigate the immunogenicity of Dato DXd (in combination with durvalumab).(Presence of ADAs for Dato-DXd (confirmatory results: positive or negative, titres).)
- To assess the safety and tolerability of neoadjuvant Dato DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy relative to neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab with or without chemotherapy in participants with previously untreated TNBC or hormone receptor-low/HER2-negative breast cancer.(Safety and tolerability will be evaluated in terms of AEs graded by CTCAE version 5.0) and in assessments including:)
Investigators
Sandeep AV
AstraZeneca Pharma India Ltd
Study Sites (12)
Loading locations...
Similar Trials
Recruiting
Phase 1
An open-label, prospective, randomised, cross-over trial to assess the pharmacokinetics of an amorphous formulation of sorafenib in mesoporous magnesium carbonate (DPH001) compared to Nexavar® (sorafenib) in healthy volunteers2024-514496-18-01Disruptive Pharma AB12
Recruiting
Phase 3
A Study Comparing AZD0120, a Dual-targeted CAR-T Against B-cell Maturation Antigen (BCMA) and CD19, Versus Standard Regimens in Participants With Relapsed Refractory Multiple Myeloma (DURGA-4)NCT07391657AstraZeneca508
Recruiting
Phase 1
A Multicentre, Randomised Phase Ib Trial to evaluate Neoadjuvant Immunotherapy Combination of Nivolumab alone or plus Ipilimumab with the IL-2 Superkine MDNA11 alone or with Tocilizumab in Patients with High-Risk, Surgically Resectable Melanoma – NEO-CYT2024-519010-31-00Fondazione Melanoma Onlus80
Not yet recruiting
Phase 3
A study to check the safety and effectiveness of a collagen eye matrix in people with corneal ulcersCTRI/2026/01/100616ACRO Biomedical Co Ltd150
Recruiting
Unknown
To evaluate the safety and effectiveness of GolimuRel in patients with Rheumatoid Arthritis, Psoriatic Arthritis and Ulcerative Colitis. Golimurel will be administered in a total of 225 patients of these three indications and safety profile will be be evaluated as primary outcome in these patients.CTRI/2025/08/092889Reliance Life Sciences Pvt Ltd225