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 (TROPION-Breast05)

JRCT ID: jRCT2061230102

Registered date:21/02/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Breast Cancer
• Date of first enrollment: 09/05/2024
• Target sample size: 625
• Countries of recruitment: Australia,Japan,Canada,Japan,China,Japan,Germany,Japan,India,Japan,Korea,Japan,Mexico,Japan,Poland,Japan,Singapore,Japan,Spain,Japan,Taiwan,Japan,Thailand,Japan,United Kingdom,Japan,United States,Japan,Vietnam,Japan
• Study type: Interventional

Intervention(s)

Arm 1: Dato-DXd + durvalumab
Arm 2: Investigator's Choice of Chemotherapy (ICC) in combination with pembrolizumab (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin)
Arm 3: Dato-DXd

Outcome(s)

• Primary Outcome: Progression Free Survival (PFS)

Secondary Outcome

Overall Survival (OS)
Objective Response Rate (ORR)
Duration of Response (DoR)
Progression-Free Survival (PFS) by Investigator assessment
Clinical Benefit Rate (CBR) at 24 weeks
Time to deterioration (TTD) in breast and arm symptoms in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab
Time to deterioration (TTD) in pain in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab
Time to deterioration (TTD) in physical functioning in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab
Time to deterioration (TTD) in GHS/QoL in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab
Time to First Subsequent Therapy (TFST)
Time to Second Subsequent Therapy (TSST)
Progression Free Survival 2 (PFS2)
Pharmacokinetics of Dato-DXd in combination with durvalumab
Immunogenicity of Dato-DXd in combination with durvalumab
Safety and tolerability of Dato-DXd + durvalumab as compared with ICC + pembrolizumab

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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.

Exclude 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.

Related Information

• Primary Sponsor: Inoguchi Akihiro
• Secondary Sponsor: AstraZeneca
• Secondary ID(s): NCT06103864