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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
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:
The primary objectives of the study are 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 and/or 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 investigator assessment of EFS.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 18 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2023-11-14
Primary completion: 2028-03-29
Study completion finish: 2030-08-28
Study type
TREATMENT
Phase
PHASE3
Trial ID
NCT06112379
Intervention or treatment
DRUG: Dato-DXd
DRUG: Durvalumab
DRUG: Pembrolizumab
DRUG: Doxorubicin
DRUG: Epirubicin
DRUG: Cyclophosphamide
DRUG: Paclitaxel
DRUG: Carboplatin
DRUG: Capecitabine
DRUG: Olaparib
Conditions
- • Breast Cancer
Find a site
Closest Location:
Research Site
Research sites nearby
Select from list below to view details:
Research Site
Darlinghurst, Not Specified, Australia
Research Site
East Melbourne, Not Specified, Australia
Research Site
Heidelberg, Not Specified, Australia
Research Site
Herston, Not Specified, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: Dato-DXd plus durvalumab
| DRUG: Dato-DXd
|
ACTIVE_COMPARATOR: Pembrolizumab plus chemotherapy
| DRUG: Pembrolizumab
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
Pathologic Complete Response (pCR) in the experimental vs control arms | pCR rate is defined as the proportion of participants who have no evidence by haematoxylin and eosin staining of residual invasive disease at the time of definitive surgery in the complete resected breast specimen and all sampled regional lymph nodes (ypT0/Tis ypN0) by blinded central evaluation. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy. The measure of interest will be the difference between the pCR rates. | At the time of definitive surgery |
Event-free survival (EFS) in the experimental vs control arms | EFS is defined as the time from the date of randomisation until the date of the first occurrence of any of the following events: disease progression precluding surgery, disease recurrence (local, regional, distant, or contralateral), second primary non-breast invasive cancer (other than squamous or basal cell skin cancer), or death by any cause (in the absence of recurrence). The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy. The measure of interest will be the Hazard Ratio of EFS. | Date of randomization to date of the EFS event, up to 68 months after the first subject randomized |
Secondary outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
Overall Survival (OS) in the experimental vs control arms | OS is defined as the time from the date of randomisation until the date of death due to any cause. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy. The measure of interest will be the Hazard Ratio of OS. | Date of randomization to date of death due to any cause, up to 82 months after the first subject randomized |
Distant disease-free survival (DDFS) in the experimental vs control arms | 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). The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy. The measure of interest will be the Hazard Ratio of DDFS. | Date of randomization to date of the DDFS event, up to 68 months after the first subject randomized |
Participant-reported breast and arm symptoms in the experimental vs. control arms | Breast and arm symptoms measured by the EORTC IL116. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy. The measure of interest is the mean between-arm difference in breast and arm symptom scores. | From Cycle 1 Day 1 of neoadjuvant treatment until pre-surgery safety FU visit (for approximately 24 weeks) or EOT - whichever occurs first. |
Participant-reported physical function in the experimental vs. control arms | Physical function measured by the PROMIS Physical Function Short Form 8c. The analysis will include all dosed participants. The measure of interest is the mean between-arm difference in physical function scores. | From Cycle 1 Day 1 of neoadjuvant treatment until pre-surgery safety FU visit (for approximately 24 weeks) or EOT - whichever occurs first, and then from Cycle 1 Day 1 of adjuvant treatment until EOT (for approximately 27 weeks). |
Participant-reported fatigue in the experimental vs. control arms | Fatigue measured by the PROMIS Fatigue Short Form 7a. The analysis will include all dosed participants. The measure of interest will be the difference on the proportions of participants reporting different levels of fatigue and mean between-arm difference in the fatigue scores. | From Cycle 1 Day 1 of neoadjuvant treatment until pre-surgery safety FU visit (for approximately 24 weeks) or EOT - whichever occurs first, and then from Cycle 1 Day 1 of adjuvant treatment until EOT (for approximately 27 weeks). |
Participant-reported Global health status/Quality of life (GHS/QoL)in the experimental vs. control arms | Global health status/Quality of life measured by EORTC IL172. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy. The measure of interest is the mean between-arm difference in GHS/QoL scores. | From Cycle 1 Day 1 of neoadjuvant treatment until pre-surgery safety FU visit (for approximately 24 weeks) or EOT - whichever occurs first, and then from Cycle 1 Day 1 of adjuvant treatment until EOT (for approximately 27 weeks). |
Pharmacokinetics of Dato-DXd (in combination with durvalumab) | Plasma concentrations of Dato-DXd (ug/ml ) | Day 1 of cycles 1,2,4,8 (Each cycle is 21 days) and at pre-surgery safety follow up visit |
Pharmacokinetics of Dato-DXd (in combination with durvalumab) | Plasma concentrations of total anti-TROP2 antibody (ug/ml ) | Day 1 of cycles 1,2,4,8 (Each cycle is 21 days) and at pre-surgery safety follow up visit |
Pharmacokinetics of Dato-DXd (in combination with durvalumab) | Plasma concentrations of DXd (MAAA-1181a) (ng/ml) | Day 1 of cycles 1,2,4,8 (Each cycle is 21 days) and at pre-surgery safety follow up visit |
Immunogenicity of Dato-DXd (in combination with durvalumab) | Presence of antidrug antibodies (ADAs) for Dato-DXd (confirmatory results: positive or negative, titres). | Day 1 of cycles 1,2,4,8 (Each cycle is 21 days) and at pre-surgery safety follow up visit |
Safety of Dato-DXd (in combination with durvalumab) | Safety and tolerability will be evaluated in terms of AEs graded by CTCAE version 5.0 | Randomization to final safety follow-up visit, either 90 days after last dose of study intervention for those who complete planned study intervention or 90 days after date of discontinuation for those who discontinue study intervention prematurely |
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