A Phase III, Open-label, Randomised Study of Datopotamab Deruxtecan (Dato-DXd) in combination with 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)

Cancer Categories

Breast

Karmanos Trial ID

2024-049

NCT ID

NCT06103864

Age Group

Adult

Scope

National

Phase

Phase III

Principal Investigator

Jailan
Elayoubi, M.D.
Oncology - Medical View Profile

Objective:

Primary Objectives:

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.

Secondary Objectives:

To demonstrate superiority of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of OS in participants with PD-L1 positive locally recurrent inoperable or metastatic TNBC
To evaluate efficacy of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of ORR in participants with PD-L1 positive locally recurrent inoperable or metastatic TNBC.
To evaluate efficacy of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of DoR in participants with PD-L1 positive locally recurrent inoperable or metastatic TNBC.
To evaluate efficacy of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of PFS as assessed by the investigator in participants with PD-L1 positive locally recurrent inoperable or metastatic TNBC.
To evaluate efficacy of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of CBR at 24 weeks in participants with PD-L1 positive locally recurrent inoperable or metastatic TNBC.
To assess TTD in breast and arm symptoms in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab.
To assess TTD in pain in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab.
To assess TTD in physical functioning in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab.
To assess TTD in GHS/QoL in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab.
To evaluate efficacy of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of TFST in participants with PD-L1 positive locally recurrent inoperable or metastatic TNBC.
To evaluate efficacy of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of TSST in participants with PD-L1 positive locally recurrent inoperable or metastatic TNBC.
To evaluate efficacy of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of PFS2 in participants with PD-L1 positive locally recurrent inoperable or metastatic TNBC.
To assess the pharmacokinetics of Dato-DXd (6 mg/kg IV Q3W) in combination with durvalumab.
To investigate the immunogenicity of Dato-DXd (6 mg/kg IV Q3W) in combination with durvalumab.

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Eligibility

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 tumour sample (primary, metastatic (location excluding bone), or locally recurrent inoperable tumour sample) collected ≤ 3 months prior to signing of informed consent (ie, start of screening).
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.

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.

Locations

Karmanos Cancer Institute - Detroit Headquarters

4100 John R
Detroit, MI 48201
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Phone: 1-800-527-6266

Karmanos Cancer Institute at Weisberg Cancer Center - Farmington Hills

31995 Northwestern Hwy
Farmington Hills, MI 48334
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Phone: 1-800-527-6266

Applicable Disease Site

Therapies, Drugs, Devices