A Study of T-DXd in Participants With or Without Brain Metastasis Who Have Previously Treated Advanced or Metastatic HER2 Positive Breast Cancer

Titre officiel

An Open-Label, Multinational, Multicentre, Phase 3b/4 Study of Trastuzumab Deruxtecan in Patients With or Without Baseline Brain Metastasis With Previously Treated Advanced/Metastatic HER2-Positive Breast Cancer (DESTINY-Breast12).

Sommaire:

This is open-label, multicentre, international study, assessing the efficacy and safety of Trastuzumab deruxtecan (T-DXd) in participants with or without brain metastasis (BMs), with previously-treated advanced/metastatic HER2-positive breast cancer whose disease has progressed on prior anti-HER2-based regimens and who received no more than 2 lines/regimens of therapy in the metastatic setting (excluding tucatinib).

Description de l'essai

Primary Outcome:

• Objective Response Rate (ORR) in Participants without BM at Baseline (Cohort 1)
• Progression-free Survival (PFS) in Participants with BM at Baseline (Cohort 2)

Secondary Outcome:

• Overall Survival (OS) in Months
• Duration of Response (DoR)
• Time to Progression
• Duration of Treatment on Subsequent Lines of Therapy
• Time to Second Progression or Death (PFS2)
• Incidence of new Symptomatic Central Nervous System (CNS) Metastasis During Treatment in Participants without BM at Baseline (Cohort 1)
• Time to Next Progression (CNS or extracranial) or Death
• Site (CNS vs extracranial vs both) of Next Progression
• Objective Response Rate in Participants with BM at Baseline (Cohort 2)
• Central Nervous System Progression-free Survival in Participants with BM at Baseline (Cohort 2)
• Time to new CNS Lesions in Participants with BM at Baseline (Cohort 2)
• Central Nervous System Objective Response Rate in Participants with BM at Baseline by ICR (Cohort 2)
• Central Nervous System Duration of Response in Participants with BM at Baseline (Cohort 2)
• European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
• Neurologic Assessment in Neuro-Oncology Scale
• Cognitive Functions Tests
• MD Anderson Symptom Inventory Brain Tumour-specific Items
• St. George's Respiratory Questionnaire - idiopathic pulmonary fibrosis version in Participants with Interstitial Lung Disease (ILD)/Pneumonitis
• Number of Participants with Adverse Events
• Number of Participants with Investigator-assessed ILD/Pneumonitis or Rate of Investigator-assessed ILD/Pneumonitis
• Number of Participants with Adverse Events with BM at Baseline

Approximately 500 eligible participants will be enrolled into 1 of 2 cohorts (250 participants in each cohort) according to the presence or absence of BMs at baseline. Cohort 1 will include participants without BM at baseline and Cohort 2 will consist of participants with BM at baseline. After study intervention discontinuation, all participants will undergo an end-of-treatment visit (within 7 days of discontinuation) and will be followed up for safety assessments 40 (+ up to 7) days after the discontinuation of all study intervention. All participants will be followed up for survival status and duration of treatment on subsequent therapies after intervention discontinuation every 3 months (± 14 days) from the date of the safety follow-up until death, withdrawal of consent, or the end of the study, as per defined in the protocol.

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