A Phase II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-tumor Efficacy of AK146D1 Combined With AK112 in Patients With Advanced Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Number of participants with dose limiting toxicities (DLTs)
研究概览
简要总结
This is a Phase II clinical study aimed at evaluating the safety, tolerability, antitumor efficacy, PK and immunogenicity of AK146D1 combined with AK112 in advanced breast cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be able to understand and voluntarily sign the written informed consent form.
- •Aged of ≥ 18 years and ≤75 years.
- •ECOG PS 0 or
- •The expected lifespan is ≥3 months.
- •Patients with histologically confirmed locally advanced, recurrent, or metastatic breast cancer who are not eligible for curative surgical resection; and who have histologically or cytologically confirmed HER2-negative disease.
- •At least one measurable lesion according to RECIST v1.
- •Patients with only bone lesions or cutaneous lesions are not ineligible for enrollment.
- •Have sufficient organ function.
- •Females patients must not be pregnant at screening or have evidence of non-childbearing potential. Agree to use medically accepted methods of contraception.
排除标准
- •Patients had breast cancer amenable to curative treatment at study enrollment.
- •Concurrent other histopathological types confirmed by tumor histology or cytology.
- •Having other active malignancies within 3 years.
- •Currently participating in another interventional clinical study.
- •Presence of active metastases to the central nervous system. For patients with asymptomatic brain metastasis or stable symptoms after treatment can be included.
- •Prior treatment with any therapy targeting Trop-2 or Nectin-4, or any chemotherapy agent targeting topoisomerase I.
- •Receipt of systemic anti-tumor therapy (including chemotherapy, immunotherapy, biological agents, etc.) within 4 weeks prior to the first dose.
- •Toxicity of previous antineoplastic therapy has not resolved to NCI CTCAE 6.0 grade 1 or lower.
- •Patients with clinically significant cardiovascular or cerebrovascular diseases or risks.
- •Patients with active autoimmune diseases requiring systemic treatment within 2 years.
- •Receipt of systemic anti-infective therapy within 2 weeks prior to the first dose.
- •Known to be positive for HIV and other infections.
- •Previous history of severe hypersensitivity reactions.
- •Live attenuated vaccines were received within 4 weeks.
- •Patients with a history of mental illness and incapacitated or limited capacity.
- •Any disease or condition that, in the opinion of the investigator, would compromise patient safety or interfere with study assessments.
研究组 & 干预措施
Arm A
Participants in this group will receive AK146D1 combined with AK112 as i.v. infusion.
干预措施: AK146D1 for injection (Drug)
Arm A
Participants in this group will receive AK146D1 combined with AK112 as i.v. infusion.
干预措施: AK112 Injection (Drug)
Arm B
Participants in this group will receive AK146D1 as i.v. infusion.
干预措施: AK146D1 for injection (Drug)
结局指标
主要结局
Number of participants with dose limiting toxicities (DLTs)
时间窗: During the first 3 weeks of treatment in Safety Run-in Phase.
DLTs are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected relationship to study drug.
Number of participants with adverse events (AEs)
时间窗: From the time of signing informed consent form through 30 days(for AEs) or 90 days(for SAEs) after the last dose of study drug.
AEs refer to any untoward medical occurrence or deterioration of existing medical events after the participants sign the ICFs, whether or not considered related to the study treatment.
Objective Response Rate (ORR) assessed by investigator per RECIST v1.1
时间窗: Up to approximately 2 years.
ORR is the proportion of participants with complete response(CR) or partial response(PR) , assessed based on RECIST v1.1.
次要结局
- Progression Free Survival (PFS) assessed by investigator per RECIST v1.1(Up to approximately 2 years.)
- Disease Control Rate (DCR) assessed per RECIST v1.1(Up to approximately 2 years.)
- Duration of response (DoR) assessed by the investigator per RECIST v1.1(Up to approximately 2 years.)
- Time to response (TTR) assessed by the investigator per RECIST v1.1(Up to approximately 2 years.)
- Overall survival (OS)(Up to approximately 2 years.)
- Serum PK concentration of AK146D1 and AK112(From pre-dose to the end of the last dose, an average of 6 months.)
- Anti-drug antibodies (ADA)(From pre-dose to 30 days post end of treatment.)