2025-523204-68-00尚未招募2 期
A Phase 2, randomized, multicenter, open-label neoadjuvant study evaluating zanidatamab in combination with chemotherapy in participants with HER2-positive breast cancer
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 25
- 试验地点
- 5
- 主要终点
- Local evaluation of pCR rate in the breast and axilla (defined as ypT0/Tis ypN0 per AJCC), as determined by local site pathologist blinded to treatment assignment
研究概览
简要总结
To determine the pCR rate (ypT0/Tis ypN0) in each treatment arm (Arm A: zanidatamab + paclitaxel, Arm B: zanidatamab + docetaxel + carboplatin, Arm C: trastuzumab + pertuzumab + docetaxel + carboplatin)
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 at least 18 years of age or of the legal adult age per local standard at the time of signing the informed consent.
- •Participant agrees to the following based on sex assigned at birth.
- •Male participants are eligible to participate if they agree to the following during the intervention period and for at least 7 months after the last dose of all study interventions or the contraception period for the chemotherapy per local guidance/standard practice, whichever is longer.
- •A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: o Is a WONCBP as defined in Appendix 5 Contraceptive and Barrier Guidance. OR − Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of < 1% per year), with low user dependency or a highly effective method that is user dependent OR 2 effective nonhormonal contraceptive methods that are user dependent, as described in Table 16 of Appendix 5 Contraceptive and Barrier Guidance, during the study intervention period and for at least 7 months after the last dose of all study interventions. The investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first 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 4 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 as described in Section 10.1.3, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
- •Has Stage II or III (according to AJCC cancer staging manual anatomic staging table, edition 8) histologically confirmed invasive breast carcinoma. A minimum tumor size of 2 cm determined by imaging is required (for participants whose tumors are node negative or node positive). Participants with inflammatory breast cancer (T4d) are eligible.
- •Has histologically confirmed HER2-positive breast cancer according to ASCO/CAP Guidelines
- •Has a known HR status of the primary tumor performed by local immunohistochemical methods according to the institution standard protocol. Participants may have HR-positive or HR-negative disease, as defined by ASCO-CAP guidelines.
- •Participants with multifocal or multicentric disease are eligible if the largest tumor (which must be larger than or equal to 2 cm in diameter) is HER2-positive, and the treating physician has determined the participant should be treated as HER2-positive.
- •Agrees to undergo a mastectomy or BCS after neoadjuvant therapy.
- •Has an ECOG performance status of 0 or
- •The participant meets the baseline laboratory criteria
- •The participant has LVEF ≥ 50% as determined by either ECHO or MUGA obtained within 4 weeks prior to first dose of study intervention.
排除标准
- •Has Stage IV (metastatic) breast cancer.
- •Was treated with chemotherapy, anti-HER2 therapy, radiation therapy, endocrine therapy, or experimental therapy for invasive breast cancer (or DCIS if ipsilateral as the invasive breast cancer).
- •Is planning to receive concurrent therapy with any other investigational agent or anticancer therapy not specified in the protocol prior to the EOT Visit, including chemotherapy; radiotherapy (except for adjuvant radiotherapy for breast cancer after completion of chemotherapy); immunotherapy; or biological, hormonal or targeted anticancer therapy. Estrogen replacement therapy is not permitted in participants with HR-positive tumors.
- •Receipt of a live vaccine within 4 weeks prior to enrollment.
- •Female participants who are breastfeeding or pregnant and female and male participants planning a pregnancy.
- •Has a known hypersensitivity to any components of the study interventions, including chemotherapy.
- •Has bilateral breast cancer.
- •Has a history (≤ 6 months before the start of treatment) of any severe and/or uncontrolled medical conditions or other conditions that, in the opinion of the investigator, could affect the participant’s involvement in the study.
- •Has uncontrolled hypertension (systolic > 180 mm Hg and/or diastolic > 100 mm Hg) or clinically significant (ie, active) cardiovascular disease: cerebrovascular accident/stroke or myocardial infarction within 6 months prior to the first dose of study intervention, ventricular arrhythmia requiring therapy, or congestive heart failure of New York Heart Association (NYHA) Class II or higher.
- •Has significant symptoms (Grade ≥ 2) from peripheral neuropathy.
- •Has an active uncontrolled (febrile within the last 48 hours; no evidence of hypotension; no ongoing systemic sequela) infection (≥ Grade 2).
- •Has a history of life-threatening hypersensitivity to monoclonal antibodies or to recombinant proteins or excipients in the drug formulation of zanidatamab or other study interventions.
- •Known active hepatitis B or C infection.
- •Has another malignancy diagnosed within the last 5 years. Exceptions include previously treated nonmelanomatous skin cancers, carcinoma in-situ, and melanoma in-situ.
结局指标
主要结局
Local evaluation of pCR rate in the breast and axilla (defined as ypT0/Tis ypN0 per AJCC), as determined by local site pathologist blinded to treatment assignment
Local evaluation of pCR rate in the breast and axilla (defined as ypT0/Tis ypN0 per AJCC), as determined by local site pathologist blinded to treatment assignment
次要结局
- Frequency of discontinuations of treatment due to TEAEs
- Pathologic response by RCB classification and score (per NeoSTEEP criteria)
- Incidence, nature, and severity of TEAEs
- Ovarian function in premenopausal women with ovaries as assessed by clinical measures and laboratory biomarkers
- Rate of participants who receive surgery as intended
- Rate of BCS in participants without inflammatory breast cancer
- EFS, defined as time from randomization to disease progression, disease recurrence (local, regional, distant, or contralateral [invasive]), or death from any cause
- Overall Survival, defined as time from randomization to death from any cause
- The frequency and severity of symptomatic AEs as assessed by the PRO-CTCAE and EORTC Item Library prior to first dose of study intervention and during the on-treatment period
- The percentage of all treated participants, as treated, reporting each level of side-effect bother while on treatment, based on the FACIT-GP5
- Serum concentrations of zanidatamab
- Frequency, duration, and time of onset of anti-zanidatamab antibodies and neutralizing antibodies, if applicable
研究者
Medical Monitor
Scientific
Jazz Pharmaceuticals Ireland Limited
研究点 (5)
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