Phase I/II, Open-label, Dose Escalation and Dose Expansion Study to Evaluate Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of AZD2936 Anti-TIGIT/Anti-PD-1 Bispecific Antibody in Participants With Advanced or Metastatic NSCLC
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 212
- 试验地点
- 40
- 主要终点
- Percentage of participants with adverse events (AEs) and immune mediated AEs (imAEs), serious AEs (SAEs), dose limiting toxicities (DLTs), vital signs, and abnormal laboratory parameters
研究概览
简要总结
This is a Phase I/II study designed to evaluate if experimental anti-TIGIT/anti-PD-1 bispecific antibody rilvegostomig (AZD2936) is safe, tolerable and efficacious in participants with Advanced or Metastatic Non-small Cell Lung Cancer.
详细描述
This is a first-time-in-human (FTIH), open-label, multicenter, multi-part, dose-escalation and dose-expansion study to evaluate the safety, pharmacokinetics (PK), pharmacodynamics, and efficacy of rilvegostomig (AZD2936) in adult participants with stage III unresectable or stage IV NSCLC. The study includes 4 parts: Part A (dose escalation) and Parts B-E (dose expansion).
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 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent
- •Aged 18 or above
- •Part A and Part B: Unresectable stage III or stage IV squamous or non-squamous NSCLC not amenable to curative surgery or radiation. Part C and Part D: Stage IV squamous or non-squamous NSCLC not amenable to curative surgery or radiation. Part E: Stage IV squamous NSCLC not amenable to curative surgery or radiation.
- •Documented PD-L1 expression by PD-L1 IHC per local report.
- •Part A and Part B: Confirmed progression during treatment with a CPI-including regimen.
- •Part C and Part D: No prior I/O treatment for metastatic NSCLC.
- •Part E: No prior treatment for metastatic NSCLC.
- •ECOG performance status of 0 or 1 at enrolment.
- •Life expectancy of ≥ 12 weeks at enrolment.
- •Have at least 1 measurable lesion per RECIST v1.
- •Adequate bone marrow, liver and kidney function
排除标准
- •Sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusion
- •Documented test result for any other known genomic alteration for which a targeted therapy is approved in first line per local standard of care (e.g. ROS1, NTRK fusions, BRAF, V600E mutation)
- •Previous treatment with an anti-TIGIT therapy
- •Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment.
- •Part A and Part B: Primary or secondary resistance after treatment with 2 or more regiments including a CPI.
- •Part C and Part D: Any prior systemic treatment with an immune oncology agent (prior administration of immune-oncology agent for curative intent to treat other invasive malignancy is permitted).
- •Treatment with one previous systemic chemotherapy will be allowed.
- •Part E: Any prior systemic treatment for metastatic NSCLC, including but not limited to chemotherapy, anti-PD-1, anti-PD-L1, anti-CTLA-
- •Symptomatic central nervous system (CNS) metastasis.
- •Thromboembolic event within 3 months prior to enrolment.
- •Other invasive malignancy within 2 years prior to screening.
研究组 & 干预措施
Dose Expansion Part E: treatment Naive Squamous NSCLC
Rilvegostomig IV monotherapy
干预措施: AZD2936 (Drug)
Dose Escalation Part A: Checkpoint inhibitor (CPI) experienced Non-small Cell Lung Cancer (NSCLC)
Rilvegostomig Intravenous (IV) monotherapy
干预措施: AZD2936 (Drug)
Dose Expansion Part B: CPI experienced NSCLC
Rilvegostomig IV monotherapy
干预措施: AZD2936 (Drug)
Dose Expansion Part D: CPI Naive NSCLC
Rilvegostomig IV monotherapy
干预措施: AZD2936 (Drug)
Dose Expansion Part C: CPI Naive NSCLC
Rilvegostomig IV monotherapy
干预措施: AZD2936 (Drug)
结局指标
主要结局
Percentage of participants with adverse events (AEs) and immune mediated AEs (imAEs), serious AEs (SAEs), dose limiting toxicities (DLTs), vital signs, and abnormal laboratory parameters
时间窗: Part A, B, C, D and E: From the time of informed consent until 90 days after the last dose of rilvegostomig
A DLT is a toxicity defined by the study protocol that occurs from the first dose of study intervention up to the end of the DLT evaluation period that is assessed as clearly unrelated to the primary disease or intercurrent illness.
Rate of rilvegostomig discontinuation due to toxicity
时间窗: Part A, B, C, D and E: From first dose to the last dose of rilvegostomig (an average of 6 months)
Percentage of participants with AEs leading to discontinuation of rilvegostomig
Objective Response Rate (ORR)
时间窗: Part B, C, D and E: From first dose of rilvegostomig to progressive disease (PD) or death in the absence of disease progression (approximately 2 years)
Percentage of participants with a confirmed Complete Response (CR) or Partial Response (PR) according to RECIST v1.1
次要结局
- ORR(Part A: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years).)
- Disease control rate (DCR)(Part A, B, C, E: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years). Part D: From randomization to PD or death in the absence of disease progression (approximately 2 years).)
- Duration of response (DoR)(Part A, B, C, D and E: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years).)
- Durable response rate (DRR)(Part A, B, C, D and E: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years).)
- Progression-free survival (PFS)(Part B, C, E: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years). Part D: From randomization to PD or death in the absence of disease progression (approximately 2 years).)
- Measure the receptor occupancy (RO) of TIGIT and PD-1 on peripheral blood(Part A, B: From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B.)
- PK of rilvegostomig: Maximum plasma concentration of the study drug (Cmax)(From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.)
- PK of rilvegostomig: Area under the concentration-time curve (AUC)(From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.)
- PK of rilvegostomig: Clearance(From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.)
- PK of rilvegostomig: Terminal elimination half-life (t 1/2)(From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.)
- Incidence of anti-drug antibodies (ADA) against rilvegostomig in serum(From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.)