2025-520582-51-00尚未招募3 期
An Open-label, Randomized, Phase 3 Study to Evaluate Patritumab Deruxtecan Monotherapy versus Treatment of Physician’s Choice in Hormone Receptor-positive, HER2-negative Unresectable Locally Advanced or Metastatic Breast Cancer (HERTHENA-Breast04)
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 211
- 试验地点
- 45
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
- To compare patritumab deruxtecan (HER3-DXd) to TPC with respect to PFS per RECIST 1.1 as assessed by BICR in all participants.
- To compare HER3-DXd to TPC with respect to OS in all participants.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Has a diagnosis of hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) invasive breast carcinoma that is either locally advanced disease not amenable to resection with curative intent (herein called unresectable) or metastatic disease not treatable with curative intent
- •Has centrally-confirmed HR+ and HER2- results and human epidermal growth factor receptor 3 (HER3) evaluable results from a biopsy obtained from a distant metastatic site or a locally advanced lesion on or after the most recent line of therapy (with certain exceptions)
- •Must have had progression or recurrence on prior cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor + endocrine therapy (ET) with one of the following: a. Radiographic disease progression, as assessed by the investigator, on CDK4/6 inhibitor + ET as first line (1L) for treatment of unresectable locally advanced or metastatic HR+/HER2- breast cancer. CDK4/6 inhibitor + ET must be the only line of therapy received in the advanced setting, or b. Disease recurrence, either radiographic and/or confirmed histologically via biopsy as assessed by the investigator, while on adjuvant ET in combination with a CDK4/6 inhibitor or within 24 months from the date of last dose of adjuvant CDK4/6 inhibitor
- •Is determined by the investigator to be a candidate for at least 1 treatment of physician’s choice (TPC) option
- •Has measurable disease per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) as assessed by the local site investigator/radiology
- •Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy
- •Has an Eastern Cooperative Oncology Group performance status of 0 or 1 assessed within 7 days before randomization
排除标准
- •Has breast cancer amenable to treatment with curative intent
- •Has ≥Grade 2 peripheral neuropathy
- •Has received prior treatment with an anti-HER3 antibody and/or antibody-drug conjugate that consists of a topoisomerase I inhibitor (e.g., T-DXd) or any other topoisomerase I inhibitor therapy
- •Has received prior systemic anticancer therapy within 4 weeks (or 5 half-lives, whichever is shorter) before randomization. Participants previously treated with ET plus a CDK4/6 inhibitor may participate as long as at least 2 weeks have elapsed since the last dose of therapy was administered.
- •Has received prior radiotherapy for non-central nervous system disease, or required corticosteroids for radiation-related toxicities, within 14 days of the first dose of study intervention
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
- •Has known additional malignancy that is progressing or has required active treatment within the past 3 years
- •Has severe hypersensitivity (≥Grade 3) to HER3-DXd and/or any of its excipients
- •Has severe hypersensitivity (≥Grade 3) to all the available TPC and/or any of their excipients
- •Is eligible to receive additional endocrine-based treatment in the advanced setting as determined by the investigator. Patients with alterations/mutations in phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PI3KCA), phosphatase and tensin homolog (PTEN), alpha-serine/threonine kinase (AKT), or estrogen receptor 1 (ESR1) who are deemed suitable for second line (2L) treatment with ET in combination with targeted therapy, where available, are not eligible
- •Has a known germline BReast CAncer gene (BRCA) mutation (deleterious or suspected deleterious) where poly adenosine diphosphate-ribose polymerase (PARP) inhibitor(s) is a potential treatment option (i.e., available and not medically contraindicated)
- •Has current visceral crisis or is at risk for impending visceral crisis that has or may cause imminent organ compromise and/or other life-threatening complications
- •Has any of the following: a pulse oximeter reading <92% at rest, or requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
- •Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
- •Has clinically significant corneal disease
- •Has received prior chemotherapy for unresectable locally advanced or metastatic breast cancer
- •Has history of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids, has current pneumonitis/interstitial lung disease, or has suspected ILD/pneumonitis
结局指标
主要结局
Progression Free Survival (PFS)
Progression Free Survival (PFS)
Overall Survival (OS)
Overall Survival (OS)
次要结局
- Objective Response Rate (ORR)
- Duration of Response (DOR)
- Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status-Quality of Life Score
- Change from Baseline in EORTC QLQ-C30 Physical Functioning Score
- Change from Baseline in EORTC QLQ-C30 Emotional Functioning Score
- Change from Baseline in EORTC QLQ-C30 Pain Score
- Time to First Deterioration (TTD) in EORTC QLQ-C30 Global Health Status-Quality of Life Score
- TTD in EORTC QLQ-C30 Physical Functioning Score
- TTD in EORTC QLQ-C30 Emotional Functioning Score
- TTD in EORTC QLQ-C30 Pain Score
- Number of Participants Who Experience an Adverse Event (AE)
- Number of Participants Who Discontinue Study Treatment Due to an AE
研究者
Preeti K Sudheendra
Scientific
Merck Sharp & Dohme LLC
研究点 (45)
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