2023-508960-31-00招募中3 期
A Phase 3, randomized, open-label, multicenter, controlled study to evaluate the efficacy and safety of zanidatamab in combination with physician’s choice chemotherapy compared to trastuzumab in combination with physician’s choice chemotherapy for the treatment of participants with metastatic HER2-positive breast cancer who have progressed on, or are intolerant to, previous trastuzumab deruxtecan treatment
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 264
- 试验地点
- 63
- 主要终点
- Progression-free survival per RECIST version 1.1, assessed by BICR
研究概览
简要总结
Compare the efficacy of zanidatamab plus chemotherapy versus trastuzumab plus chemotherapy
研究设计
- 分配方式
- Randomized
- 主要目的
- Section 1
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Is 18 years of age or of the legal adult age per local standard at the time of signing the informed consent.
- •Has creatinine clearance ≥ 30 mL/minute as calculated per local institutional guidelines.
- •Has LVEF ≥ 55% as determined by either echocardiogram or MUGA obtained within 4 weeks before the first dose of study intervention.
- •Has ECOG performance status of 0 or
- •Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 7 months after the last dose of study intervention or the contraception period for the combination chemotherapy of choice per local guidance/standard practice. This requirement aligns with the contraception period recommended for trastuzumab and is longer than the recommended contraception period for zanidatamab, which is 5 months, and for all other allowed chemotherapy options.
- •A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: - Is a WONCBP; - Is a WOCBP and using a contraceptive method that is highly effective during the study intervention period and for at least 7 months after the last dose of study intervention. This requirement aligns with the contraception period recommended for trastuzumab and is longer than the recommended contraception period for zanidatamab, which is 5 months, and for all other allowed chemotherapy options. Therefore, 7 months is considered sufficient to collect details of all pregnancies.
- •Is capable of giving signed informed consent
- •Has histologically confirmed HER2-positive breast cancer according to ASCO–CAP Guidelines as evaluated by a central laboratory
- •Participants with unresectable or metastatic HER2 positive breast cancer who have progressed on, or are intolerant to, previous T-DXd treatment.
- •Has measurable disease per RECIST version 1.
- •Is eligible to receive one of the chemotherapy options listed in the physician’s choice of chemotherapy (eribulin, gemcitabine, vinorelbine, or capecitabine).
- •Participants with history of treated or clinically inactive CNS metastases are eligible
- •Has a life expectancy of at least 6 months, in the opinion of the investigator.
- •Has adequate hematologic parameters
- •Has adequate hepatic function
排除标准
- •Has known or suspected leptomeningeal disease.
- •Has uncontrolled or significant cardiovascular disease
- •Has toxicity related to prior cancer therapy that has not resolved to ≤ Grade 1
- •Has uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
- •Has known HIV infection
- •Has active hepatitis B or C infection.
- •Has an active SARS-CoV-2 infection.
- •Has a history of life-threatening hypersensitivity to monoclonal antibodies or to recombinant proteins or excipients in the drug formulation of zanidatamab.
- •Is unable to receive trastuzumab treatment due to medical contraindications
- •Participants known to have a complete lack of the enzyme dihydropyrimidine dehydrogenase who are assigned to receive chemotherapy capecitabine in combination with the study treatment.
- •Has any serious underlying medical or psychiatric condition that would impair the ability of the participant to receive or tolerate the planned treatment at the investigational site.
- •Has any condition that would prevent treatment with the physician’s choice of chemotherapy.
- •Has any issue or condition that in the opinion of the investigator would contraindicate the participant’s participation in the study or confound the results of the study
- •Has a history of prior allogeneic bone marrow, stem cell, or solid organ transplantation.
- •Was treated with any local or systemic antineoplastic therapy (including hormonal therapies for breast cancer) or any investigational therapy within 4 weeks or 5 half-lives (whichever is longer) prior to randomization
- •Has a history of trauma or major surgery within 4 weeks prior to randomization.
- •Has a known hypersensitivity to any components of the study drugs, including chemotherapy.
- •Female participants who are breastfeeding or pregnant, and female and male participants planning a pregnancy.
结局指标
主要结局
Progression-free survival per RECIST version 1.1, assessed by BICR
Progression-free survival per RECIST version 1.1, assessed by BICR
次要结局
- Overall survival
- Confirmed ORR per RECIST version 1.1, assessed by BICR
- DOR per RECIST version 1.1, assessed by BICR
- PFS per RECIST version 1.1, assessed by investigator
- Confirmed ORR per RECIST version 1.1, assessed by investigator
- DOR per RECIST version 1.1, assessed by investigator
- Frequency of TEAEs and SAEs as graded by NCI CTCAE version 5.0
- Frequency of dose reductions
- Frequency of discontinuations of treatment due to TEAEs
- Serum concentrations of zanidatamab as a function of time postdosing
- Frequency, duration, and time of onset of anti-zanidatamab antibodies and neutralizing antibodies, if applicable
- Descriptive summary of the proportion of all treated patients, as treated, reporting symptomatic AEs while on treatment based on the PRO‑CTCAE and EORTC Item Library
- Descriptive summary of the proportion of all treated patients, as treated, reporting overall side-effect bother on the FACIT-GP5
- The proportion of treated patients, as treated, with maintained or improved physical function while on treatment based on the physical functioning subscale of the EORTC QLQ-C30
- The proportion of treated patients, as treated, with maintained or improved role function while on treatment based on the role functioning subscale of the EORTC QLQ-C30
- Change from baseline and time to worsening of select scores from the EORTC QLQC30, EORTC IL341, and PGI-S
研究者
Medical Monitor
Scientific
Jazz Pharmaceuticals Ireland Limited
研究点 (63)
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