This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT06103864
Recruitment Status : Recruiting
First Posted : October 27, 2023
Last Update Posted : April 19, 2024
Sponsor:
Collaborator:
Daiichi Sankyo
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE October 23, 2023
First Posted Date  ICMJE October 27, 2023
Last Update Posted Date April 19, 2024
Actual Study Start Date  ICMJE November 23, 2023
Estimated Primary Completion Date September 1, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 23, 2023)
Progression Free Survival (PFS) [ Time Frame: 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). ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 23, 2023)
  • Overall Survival (OS) [ Time Frame: From randomisation until the date of death due to any cause (anticipated to be up to 64 months). ]
    OS is defined as the time from randomisation until the date of death due to any cause.
  • Objective Response Rate (ORR) [ Time Frame: From randomisation up until progression (anticipated to be up to 33 months). ]
    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.
  • Duration of Response (DoR) [ Time Frame: 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). ]
    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.
  • Progression-Free Survival (PFS) by Investigator assessment [ Time Frame: 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). ]
    PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by investigator, or death due to any cause.
  • Clinical Benefit Rate (CBR) at 24 weeks [ Time Frame: From randomisation up until progression, or the last evaluable assessment in the absence of progression (anticipated to be up to 33 months). ]
    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.
  • Time to deterioration (TTD) in breast and arm symptoms in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab [ Time Frame: From the date of randomisation to the date of deterioration (from randomization to 18 weeks post-progression). ]
    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.
  • Time to deterioration (TTD) in pain in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab [ Time Frame: Time from the date of randomisation to the date of deterioration (from randomization to 18 weeks post-progression). ]
    TTD in pain as measured by the EORTC IL199.
  • Time to deterioration (TTD) in physical functioning in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab [ Time Frame: From the date of randomisation to the date of deterioration (from randomization to 18 weeks post-progression). ]
    TTD in physical function as measured by the PROMIS Short Form v2.0 - Physical Function 8c.
  • Time to deterioration (TTD) in GHS/QoL in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab [ Time Frame: From the date of randomisation to the date of deterioration (from randomization to 18 weeks post-progression). ]
    TTD in GHS/QoL as measured by the GHS/QoL scale from EORTC IL172.
  • Time to First Subsequent Therapy (TFST) [ Time Frame: 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). ]
    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.
  • Time to Second Subsequent Therapy (TSST) [ Time Frame: 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). ]
    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.
  • Progression Free Survival 2 (PFS2) [ Time Frame: 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). ]
    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.
  • Pharmacokinetics of Dato-DXd in combination with durvalumab [ Time Frame: From first dose to end of treatment (anticipated to be up to 33 months). ]
    Concentration of Dato-DXd, total anti-TROP2 antibody, and DXd (payload) in plasma.
  • Immunogenicity of Dato-DXd in combination with durvalumab [ Time Frame: From first dose to end of treatment safety follow-up (anticipated to be up to 33 months). ]
    Presence of antidrug antibodies for Dato-DXd (confirmatory results: positive or negative, titres).
  • Safety and tolerability of Dato-DXd + durvalumab as compared with ICC + pembrolizumab [ Time Frame: From first dose to end of treatment safety follow-up (anticipated to be up to 33 months). ]
    Safety and tolerability will be evaluated in the safety population in terms of AEs.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE A Phase III, Open-label, Randomised Study of Datopotamab Deruxtecan (Dato-DXd) With or Without Durvalumab Compared With Investigator's Choice of Chemotherapy (Paclitaxel, Nab-paclitaxel or Gemcitabine + Carboplatin) in Combination With Pembrolizumab in Patients With PD-L1 Positive Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer (TROPION-Breast05)
Brief Summary 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.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Participants will be randomised either 1:1 to Arm 1 (Dato-DXd + durvalumab) and Arm 2 (ICC + pembrolizumab), or in selected countries, 1:1:1 to Arms 1, 2 and 3 (Dato-DXd monotherapy). Once approximately 75 participants are randomised to Arm 3, this cohort will close, and all countries will continue with a 1:1 randomisation strategy for Arms 1 and 2.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: Dato-DXd
    Provided in 100mg vials. IV infusion. Experimental drug.
    Other Name: Datopotamab deruxtecan (Dato-DXd, DS-1062a)
  • Drug: Durvalumab
    Provided in 500mg vials. IV infusion. Experimental drug.
    Other Name: MEDI4736
  • Drug: Paclitaxel
    IV infusion. Active comparator.
  • Drug: Nab-paclitaxel
    IV infusion. Active comparator.
  • Drug: Gemcitabine
    IV infusion. Active comparator.
  • Drug: Carboplatin
    IV infusion. Active comparator.
  • Drug: Pembrolizumab
    IV infusion. Active comparator.
Study Arms  ICMJE
  • Experimental: Dato-DXd + durvalumab
    Arm 1: Dato-DXd + durvalumab
    Interventions:
    • Drug: Dato-DXd
    • Drug: Durvalumab
  • Active Comparator: Investigator's Choice of Chemotherapy (ICC) in combination with pembrolizumab
    Arm 2: Investigator's Choice of Chemotherapy (ICC) in combination with pembrolizumab (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin)
    Interventions:
    • Drug: Paclitaxel
    • Drug: Nab-paclitaxel
    • Drug: Gemcitabine
    • Drug: Carboplatin
    • Drug: Pembrolizumab
  • Experimental: Dato-DXd
    Arm 3: Dato-DXd
    Intervention: Drug: Dato-DXd
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 23, 2023)
625
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 23, 2029
Estimated Primary Completion Date September 1, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria

  • Histologically or cytologically documented locally recurrent inoperable, which cannot be treated with curative intent, or metastatic TNBC, as defined by the ASCO-CAP guidelines.
  • ECOG PS 0 or 1.
  • All participants must provide a FFPE metastatic or locally recurrent inoperable tumour sample.
  • PD-L1 positive TNBC based on results from an appropriately validated investigational PD-L1 (22C3) assay (CPS ≥ 10) from a sponsor designated central laboratory.
  • No prior chemotherapy or targeted systemic anti-cancer therapy for metastatic or locally recurrent inoperable breast cancer.

    - Patients with recurrent disease will be eligible if they have completed treatment for Stage I-III breast cancer, if indicated, and ≥6 months have elapsed between completion of treatment with curative intent and the first documented recurrence.

  • Eligible for one of the chemotherapy options listed as ICC (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin).
  • Measurable disease as per RECIST 1.1.
  • Adequate bone marrow reserve and organ function.
  • Male and female participants of childbearing potential must agree to use protocol-specified method(s) of contraception.

Key Exclusion Criteria

  • As judged by investigator, severe or uncontrolled medical conditions including systemic diseases, history of allogeneic organ transplant and active bleeding diseases, ongoing or active infection, significant cardiac or psychological conditions.
  • History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before Cycle 1 Day 1 and of low potential risk for recurrence.
  • Neoplastic spinal cord compression or active brain metastases, leptomeningeal carcinomatosis or history of leptomeningeal carcinomatosis.

    - Participants with treated clinically inactive brain metastases that are no longer symptomatic, who require no treatment with corticosteroids or anticonvulsants, may be included in the study if they have recovered from acute toxic effects of radiotherapy.

  • Uncontrolled infection requiring IV antibiotics, antivirals or antifungals.
  • Active or uncontrolled hepatitis B or C virus infection.
  • Known HIV infection that is not well controlled.
  • Uncontrolled or significant cardiac disease.
  • History of non-infectious ILD/pneumonitis (including radiation pneumonitis) that required steroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
  • Severe pulmonary function compromise.
  • Clinically significant corneal disease.
  • Active or prior documented autoimmune or inflammatory disorders.
  • Prior exposure to any treatment including ADC containing a chemotherapeutic agent targeting topoisomerase I and TROP2-targeted therapy.
  • Any concurrent anti-cancer treatment.
  • Participants with a known severe hypersensitivity to PD-1/PD-L1 inhibitors or Dato-DXd.
  • Currently pregnant (confirmed with positive pregnancy test), breastfeeding or planning to become pregnant.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Listed Location Countries  ICMJE Argentina,   Australia,   Brazil,   Canada,   China,   France,   Germany,   India,   Italy,   Japan,   Korea, Republic of,   Mexico,   Philippines,   Poland,   Singapore,   South Africa,   Spain,   Taiwan,   Thailand,   Turkey,   United Kingdom,   United States,   Vietnam
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT06103864
Other Study ID Numbers  ICMJE D7630C00001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

"Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
URL: https://vivli.org/
Current Responsible Party AstraZeneca
Original Responsible Party Same as current
Current Study Sponsor  ICMJE AstraZeneca
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Daiichi Sankyo
Investigators  ICMJE Not Provided
PRS Account AstraZeneca
Verification Date April 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP