An Exploratory, Multi-cohort Phase II Study of Combination Therapy of AK112 With Chemotherapy and/or Olaparib in Platinum-sensitive Ovarian Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Progression-free survival (PFS) assessed by investigator per RECIST v1.1
研究概览
简要总结
An Exploratory, Multi-cohort Phase II Study of combination therapy of AK112 with chemotherapy and/or olaparib in platinum-sensitive ovarian cancer(PSOC)
详细描述
This is a Phase 2, open label, multicohort, multicenter study designed to evaluate the efficacy and safety of combination of AK112 with chemotherapy and/or olaparib in platinum-sensitive ovarian cancer. AK112 is a bispecific monoclonal antibody targeting VEGF and PD-1.
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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Signs the written informed consent form.
- •Female participants who are at least 18 years of age on the day of signing informed consent with.
- •ECOG of 0 or
- •Life expectancy ≥3 months.
- •Histologically documented epithelial and non-mucinous PSOC. PSOC was defined as radiographic progression greater than 6 months from last dose of platinum-based chemotherapy.
- •If breast cancer susceptibility gene (BRCA) positive participants must have received prior treatment with a poly adenosine phosphate-ribose polymerase inhibitor (PARPi).
- •Ovarian cancer includes ovarian cancer, fallopian tube cancer and primary peritoneal cancer in this study, unless otherwise specified.
- •Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as determined by the site study team.
- •Be able to provide formalin fixed, paraffin-embedded (FFPE) tumor tissue.
- •Has adequate organ function.
- •All subjects of reproductive potential must agree to use an effective method of contraception, during and for 6 months after the last dose of study treatment.
排除标准
- •Other pathological types such as mucinous cancer, sex cord stromal cell tumor, etc.
- •Presence of central nervous system (CNS) metastases or carcinomatous meningitis.
- •Subjects with uncontrollable pleural, pericardial, or peritoneal effusion requiring repeated drainage.
- •Subjects with other active malignancies within 3 years prior to randomization.
- •Received systemic anti-tumor therapy within 2 weeks prior to randomization.
- •Any prior treatments targeting the mechanism of tumor immunity.
- •Major surgical , open biopsy or significant trauma within 4 weeks prior to randomization; or elective major surgical treatment required during the study.
- •Active or potentially recurrent autoimmune disease.
- •Subjects who require systemic treatment with glucocorticoid (>10 mg/day of prednisone or equivalent glucocorticoid) or other immunosuppressive agents within 14 days prior to randomization.
- •Receiving live vaccines within 4 weeks prior to randomization.
- •Known primary or secondary immunodeficiencies, including testing positive for human immunodeficiency virus (HIV) antibodies.
- •Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
- •Known history of interstitial lung disease or non-infectious pneumonitis.
- •Serious infections requiring hospitalization.
- •Presence of active infection requiring systemic therapy.
- •Subjects with active hepatitis B and active viral hepatitis C.
- •Active or documented inflammatory bowel diseases, active diverticulitis.
- •Subjects with clinically significant cardio-cerebrovascular disease.
- •Unresolved toxicities from prior anticancer therapy.
- •History of severe hypersensitivity reactions to other mAbs.
- •Pregnant or lactating women.
- •Any condition that, in the opinion of the Investigator, may result in a risk when receiving the study drug.
- •Exclusion Criteria for combination therapy-Related: For cohort 1: Known contraindications or allergy to paclitaxel or carboplatin. For Cohorts 1-10A, Cohort 1-20A, and Cohort 2: Known contraindications or allergy to Olaparib.
- •Exclusion Criteria for AK112-Related: Known contraindications or allergy to any component of VEGF mABs or any medical conditions that affect the safety of AK112.
研究组 & 干预措施
Cohort 1-10 (BRCAm)
AK112(10mg/kg)+chemo for 4-6 cycles, AK112 (10mg/kg)+Olaparib maintenance
干预措施: AK112 low dose (Drug)
Cohort 1-10 (BRCAm)
AK112(10mg/kg)+chemo for 4-6 cycles, AK112 (10mg/kg)+Olaparib maintenance
干预措施: Chemotherapy (Drug)
Cohort 1-10 (BRCAm)
AK112(10mg/kg)+chemo for 4-6 cycles, AK112 (10mg/kg)+Olaparib maintenance
干预措施: Olaparib (Drug)
Cohort 1-10B (non-BRCAm)
AK112(10mg/kg)+chemo for 4-6cycles, AK112(10mg/kg) maintenance
干预措施: AK112 low dose (Drug)
Cohort 1-10B (non-BRCAm)
AK112(10mg/kg)+chemo for 4-6cycles, AK112(10mg/kg) maintenance
干预措施: Chemotherapy (Drug)
Cohort 1-20A (BRCAm)
AK112(20mg/kg)+chemo for 4-6cycles, AK112(20mg/kg)+Olaparib maintenance
干预措施: Chemotherapy (Drug)
Cohort 1-20A (BRCAm)
AK112(20mg/kg)+chemo for 4-6cycles, AK112(20mg/kg)+Olaparib maintenance
干预措施: Olaparib (Drug)
Cohort 1-20A (BRCAm)
AK112(20mg/kg)+chemo for 4-6cycles, AK112(20mg/kg)+Olaparib maintenance
干预措施: AK112 high dose (Drug)
Cohort 1-20B (non-BRCAm)
AK112(20mg/kg)+chemo for 4-6cycles, AK112(20mg/kg) maintenance
干预措施: Chemotherapy (Drug)
Cohort 1-20B (non-BRCAm)
AK112(20mg/kg)+chemo for 4-6cycles, AK112(20mg/kg) maintenance
干预措施: AK112 high dose (Drug)
Cohort 2 (Prior ≥2L)
AK112(20mg/kg)+Olaparib
干预措施: Olaparib (Drug)
Cohort 2 (Prior ≥2L)
AK112(20mg/kg)+Olaparib
干预措施: AK112 high dose (Drug)
结局指标
主要结局
Progression-free survival (PFS) assessed by investigator per RECIST v1.1
时间窗: up to 2 years
PFS is defined as the time from the date of first dosing till the first documented disease progression Per RECIST v1.1 assessed by the investigator or death due to any cause, whichever occurs first.
次要结局
- Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by investigator(Up to 2 years)
- Disease control rate(DCR)assessed by investigator per RECIST v1.1(Up to 2 years)
- Duration of Response (DOR) assessed by investigator per RECIST v1.1(Up to 2 years)
- Time to Response (TTR) assessed by investigator per RECIST v1.1(Up to 2 years)
- Overall Survival(OS)(Up to 2 years)
- Number of participants with adverse event (AE)(Up to 2 years)