A Phase I/II Study of AK129 (Bispecific Antibody Targeting LAG-3 and PD-1) Monotherapy or in Combination With AK117 (Anti-CD47 Monoclonal Antibody) in Relapse or Refractory Classic Hodgkin Lymphoma With PD-1/L1 Inhibitor Treatment Failure
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 280
- 试验地点
- 1
- 主要终点
- Phase I: Number of participants with dose limiting toxicity (DLT)
研究概览
简要总结
This is a phase I/II study. All subjects are patients diagnosed with relapse or refractory (R/R) classic Hodgkin lymphoma (cHL) and has progressed on treatment with PD-1/L1 inhibitor therapy. The purpose of this study is to evaluate the safety and efficacy of AK129 (bispecific antibody targeting LAG-3 and PD-1) monotherapy or in combination with AK117 (anti-CD47 monoclonal antibody) in R/R cHL with PD-1/L1 inhibitor treatment failure.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Age ≥ 18 years old at the time of enrolment.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Expected Survival of ≥ 12 weeks.
- •Diagnosed as R/R cHL according to Lugano 2014 criteria.
- •Has progressed on treatment with PD-1/L1 inhibitior therapy.
- •Has adequate organ function.
- •All female and male subjects of reproductive potential must agree to use an effective method of contraception from the start of screening until 120 days after the last dose of study treatment.
排除标准
- •Diagnosed with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) or gray zone lymphoma.
- •Central nervous system (CNS) lymphoma involvement.
- •Known history of human T-cell leukemia virus type 1 (HTLV-1) infection.
- •Autologous hematopoietic stem cell transplantation (auto-HSCT) or chimeric antigen receptor T cell immunotherapy (CAR-T) within 90 days prior to the first dose of study treatment.
- •Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation (allo-HSCT).
- •Previous use of any agents targeting the CD47-SIRPα pathway, LAG-3 pathway, or similar targets.
- •Has other malignancies within 3 years prior to the first dose or residual lesions from other malignancies diagnosed more than 3 years ago.
- •Has an active autoimmune disease requiring systemic treatment within 2 years prior to the first dose.
- •History of active or previously confirmed inflammatory bowel disease.
- •History of interstitial lung disease requiring corticosteroid therapy, or current interstitial lung disease.
- •Has known active Hepatitis B or Hepatitis C.
- •Unresolved toxicity from previous anti-tumor treatment.
- •Uncontrolled comorbidities.
研究组 & 干预措施
AK129
Phase Ia: Subjects will receive AK129: different doses on every 2 weeks.
干预措施: AK129 (Drug)
AK129+AK117
Phase Ib: Subjects will receive: AK129: different doses on every 2 weeks, AK117: 30mg/kg on every 2 weeks.
Phase II: Subjects will receive: AK129: recommended phase II dose (RP2D) from phase Ib on every 2 weeks, AK117: 30mg/kg on every 2 weeks.
干预措施: AK129 (Drug)
AK129+AK117
Phase Ib: Subjects will receive: AK129: different doses on every 2 weeks, AK117: 30mg/kg on every 2 weeks.
Phase II: Subjects will receive: AK129: recommended phase II dose (RP2D) from phase Ib on every 2 weeks, AK117: 30mg/kg on every 2 weeks.
干预措施: AK117 (Drug)
结局指标
主要结局
Phase I: Number of participants with dose limiting toxicity (DLT)
时间窗: Within the first 28 days following the first dose of study treatment.
Any untoward medical occurrence in a subject within the first 28 days following the first dose, considered related to the study treatment.
Phase I/II: Incidence and severity of adverse events (AEs)
时间窗: Up to approximately 2 years.
Any untoward medical occurrence in a subject, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Phase I/II: Objective response rate (ORR)
时间窗: Up to approximately 2 years
The proportion of subjects achieving complete response (CR) or partial response (PR) assessed by investigator per Lugano 2014 criteria.
次要结局
- Disease control rate (DCR)(Up to approximately 2 years)
- Time to response (TTR)(Up to approximately 2 years)
- Duration of response (DoR)(Up to approximately 2 years)
- Progression-free survival (PFS)(Up to approximately 2 years)
- Overall survival (OS)(Up to approximately 2 years)
- Maximum concentration (Cmax)(Up to approximately 2 years)
- Time to maximum concentration (Tmax)(Up to approximately 2 years)
- Area under the curve (AUC)(Up to approximately 2 years)
- Half-life (T1/2)(Up to approximately 2 years)
- Anti-drug antibody (ADA)(Up to approximately 2 years)