A Phase 1a/1b, Multicenter, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, and Anti-tumour Activity of AK127 in Combination With AK104 in Subjects With Advanced or Metastatic Solid Tumours
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 5
- 主要终点
- Incidence and Nature of Adverse Events (AEs)
研究概览
简要总结
A Phase 1 study to evaluate the safety, tolerability, PK, immunogenicity, pharmacodynamics, and preliminary antitumor activity of AK127 in combination with AK104.
详细描述
This is a , Phase 1, first-in-human, multicenter, open label, dose escalation and dose expansion study designed to evaluate the safety, tolerability, PK, immunogenicity, pharmacodynamics, and preliminary antitumor activity of AK127 in combination with AK104 in subjects with advanced and metastatic solid tumours. The study comprises of 2 phases: a dose escalation phase and a dose expansion phase. Dose escalation for AK127 will occur using the 3+3+3 model given with a fixed regimen of AK104. Dose expansion will open at the discretion of the Sponsor.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
None (open Label)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written and signed informed consent
- •In Phase 1a, patients with relapsed or refractory advanced solid malignancies
- •In Phase 1b, patients must have received no more than three prior lines of systemic therapy
- •Subject must have at least one measurable lesion according to RECIST Version1.
- •Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or
- •Available archived or fresh tumor tissue
- •Adequate organ function.
- •For dose-expansion cohorts (Phase 1b), subjects must be willing to provide two fresh biopsy samples (pre-treatment and on treatment), where clinically appropriate.
- •Females of childbearing potential and non-sterilized males who are sexually active must use an effective method of contraception from screening until 120 days after final dose of investigational product.
排除标准
- •History of severe hypersensitivity reactions to other mAbs.
- •Subjects with a condition requiring systemic treatment with either corticosteroid (> 10 mg daily ) or other immunosuppressive medications within 2 weeks of study drug administration.
- •Prior use of approved or investigational anti-TIGIT, anti-PVRIG, or anti-CD96 therapy
- •Receiving any Other anticancer therapy (e.g., chemotherapy, radiotherapy, biologic or hormonal therapy for cancer treatment. etc.) within 4 weeks prior to the first dose of treatment
- •Any major surgery within 4 weeks prior to the first dose of treatment
- •Receiving agents with immunomodulatory effect within 2 weeks prior to the first dose of treatment.
- •Active or prior documented inflammatory bowel disease
- •History of organ transplant.
- •History of interstitial lung disease, noninfectious pneumonitis except for those induced by radiation therapies.
- •Known active hepatitis B or C infections or history of HIV.
- •Receipt of live attenuated vaccines within 4 weeks prior to the first dose of investigational product.
- •Patients with severe heart and lung dysfunction.
研究组 & 干预措施
Intervention/treatment
Experimental
干预措施: AK127 (Drug)
Intervention/treatment
Experimental
干预措施: AK104 (Drug)
结局指标
主要结局
Incidence and Nature of Adverse Events (AEs)
时间窗: From the time of informed consent signed through to 90 days after end of treatment
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Number of participants with a Dose Limiting Toxicity (DLT)
时间窗: Within the first six weeks of treatment
DLTs will be assessed during the first treatment cycle and assessed as having a suspected relationship to study drug according to pre-specific criteria in the protocol.
次要结局
- Objective response rate (ORR)(Up to 2 years)
- Disease control rate (DCR)(Up to 2 years)
- Progression-free survival (PFS)(Up to 2 years)
- Overall survival (OS)(Up to 2 years)
- Area under the curve (AUC) of AK127+AK104 for assessment of pharmacokinetics(From first dose of treatment through to 90 days after end of treatment)
- Maximum observed concentration (Cmax) of AK127 + AK104(From first dose of treatment through to 90 days after end of treatment.)
- Minimum observed concentration (Cmin) of AK127+AK104(From first dose of treatment through to 90 days after end of treatment)
- Number of subjects who develop detectable anti-drug antibodies (ADAs)(From first dose of treatment through to 90 days after end of treatment)