Share
Save
A Phase III Study of Dato-DXd With or Without Durvalumab Compared With Investigator's Choice of Chemotherapy in Combination With Pembrolizumab in Patients With PD-L1 Positive Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer
This is a Phase III, randomised, open-label, 3-arm, multicentre, international study assessing the efficacy and safety of Dato-DXd with or without durvalumab compared with investigator's choice chemotherapy in combination with pembrolizumab in participants with PD-L1 positive locally recurrent inoperable or metastatic TNBC.
Study details:
The primary objective of the study is to demonstrate superiority of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of PFS as assessed by BICR in participants with PD-L1 positive locally recurrent inoperable or metastatic TNBC. The study will be stratified based on geographic location (US/Canada/Europe vs. Dato-DXd monotherapy enrolling countries vs.
rest of world), disease-free interval (DFI) history (de novo vs. prior DFI 6 to 12 months vs. prior DFI \> 12 months), and prior PD-1/PD-L1 treatment for early stage TNBC (yes vs.
no). This study aims to see if Dato-DXd with durvalumab allows patients to live longer without their breast cancer getting worse, or simply to live longer, compared to patients receiving standard of care chemotherapy and pembrolizumab. This study is also looking to see how the treatment and the breast cancer affects patients' quality of life.
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: 2023-11-23
Primary completion: 2026-09-01
Study completion finish: 2029-04-23
Study type
TREATMENT
Phase
PHASE3
Trial ID
NCT06103864
Intervention or treatment
DRUG: Dato-DXd
DRUG: Durvalumab
DRUG: Paclitaxel
DRUG: Nab-paclitaxel
DRUG: Gemcitabine
DRUG: Carboplatin
DRUG: Pembrolizumab
Conditions
- • Breast Cancer
Find a site
Closest Location:
Research Site
Research sites nearby
Select from list below to view details:
Research Site
Camperdown, Not Specified, Australia
Research Site
Darlinghurst, Not Specified, Australia
Research Site
Heidelberg, Not Specified, Australia
Research Site
Melbourne, 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 + durvalumab
| DRUG: Dato-DXd
|
ACTIVE_COMPARATOR: Investigator's Choice of Chemotherapy (ICC) in combination with pembrolizumab
| DRUG: Paclitaxel
|
EXPERIMENTAL: Dato-DXd
| DRUG: Dato-DXd
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
Progression Free Survival (PFS) | PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause. The comparison will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy, receives another anticancer therapy or clinically progresses prior to RECIST 1.1 progression. However, if the participant progresses or dies immediately after 2 or more consecutive missed visits, the participant will be censored at the time of the latest evaluable assessment prior to the 2 missed visits. The measure of interest is the HR of PFS. | From randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause (anticipated to be up to 33 months). |
Secondary outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
Overall Survival (OS) | OS is defined as the time from randomisation until the date of death due to any cause. | From randomisation until the date of death due to any cause (anticipated to be up to 64 months). |
Objective Response Rate (ORR) | ORR is defined as the proportion of participants who have a CR or PR, as determined by the BICR/investigator assessment, per RECIST 1.1. | From randomisation up until progression (anticipated to be up to 33 months). |
Duration of Response (DoR) | DoR is defined as the time from the date of first documented response until date of documented progression per RECIST 1.1, as assessed by BICR/investigator assessment or death due to any cause. | From the date of first documented response until date of documented progression per RECIST 1.1, as assessed by BICR/investigator assessment or death due to any cause (anticipated to be up to 33 months). |
Progression-Free Survival (PFS) by Investigator assessment | PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by investigator, or death due to any cause. | From randomisation until progression per RECIST 1.1 as assessed by the investigator, or death due to any cause (anticipated to be up to 33 months). |
Clinical Benefit Rate (CBR) at 24 weeks | CBR at 24 weeks is defined as the percentage of participants who have a CR or PR or who have SD, per RECIST 1.1, as assessed by BICR/per investigator assessment and derived from the raw tumour data for at least 23 weeks after randomisation. | From randomisation up until progression, or the last evaluable assessment in the absence of progression (anticipated to be up to 33 months). |
Time to deterioration (TTD) in breast and arm symptoms in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab | TTD in breast symptoms and arm symptoms as measured by the arm symptoms scale from EORTC IL116 TTD is defined as time from the date of randomisation to the date of deterioration. Deterioration is defined as change from baseline that reaches a clinically meaningful deterioration threshold. | From the date of randomisation to the date of deterioration (from randomization to 18 weeks post-progression). |
Time to deterioration (TTD) in pain in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab | TTD in pain as measured by the EORTC IL199. | Time from the date of randomisation to the date of deterioration (from randomization to 18 weeks post-progression). |
Time to deterioration (TTD) in physical functioning in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab | TTD in physical function as measured by the PROMIS Short Form v2.0 - Physical Function 8c. | From the date of randomisation to the date of deterioration (from randomization to 18 weeks post-progression). |
Time to deterioration (TTD) in GHS/QoL in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab | TTD in GHS/QoL as measured by the GHS/QoL scale from EORTC IL172. | From the date of randomisation to the date of deterioration (from randomization to 18 weeks post-progression). |
Time to First Subsequent Therapy (TFST) | TFST is defined as the time from randomisation until the start date of the first subsequent anticancer therapy after discontinuation of randomised treatment, or death due to any cause. | From randomisation until the start date of the first subsequent anticancer therapy after discontinuation of randomised treatment, or death due to any cause (anticipated to be up to 64 months). |
Time to Second Subsequent Therapy (TSST) | TSST is defined as the time from randomisation until the start date of the second subsequent anticancer therapy after discontinuation of first subsequent treatment, or death due to any cause. | From randomisation until the start date of the second subsequent anti cancer therapy after discontinuation of first subsequent treatment, or death due to any cause (anticipated to be up to 64 months). |
Progression Free Survival 2 (PFS2) | PFS2 will be defined as the time from the randomisation to the earliest progression event (following the initial progression), subsequent to first subsequent therapy, or death. The date of second progression will be recorded by the investigator in the eCRF and defined according to local standard clinical practice based on radiological or clinical progression. | From the randomisation to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy, or death (anticipated to be up to 64 months). |
Pharmacokinetics of Dato-DXd in combination with durvalumab | Concentration of Dato-DXd, total anti-TROP2 antibody, and DXd (payload) in plasma. | From first dose to end of treatment (anticipated to be up to 33 months). |
Immunogenicity of Dato-DXd in combination with durvalumab | Presence of antidrug antibodies for Dato-DXd (confirmatory results: positive or negative, titres). | From first dose to end of treatment safety follow-up (anticipated to be up to 33 months). |
Safety and tolerability of Dato-DXd + durvalumab as compared with ICC + pembrolizumab | Safety and tolerability will be evaluated in the safety population in terms of AEs. | From first dose to end of treatment safety follow-up (anticipated to be up to 33 months). |
Frequently Asked Questions
Please note: some questions and answers are submitted by anonymous patients or using AI, and have not been verified by Clinrol
No questions submitted. Be the first to ask a question!