A Phase I, Multicentre, Dose Escalation and Dose Expansion Study to Investigate the Pharmacokinetics and Safety of Subcutaneous Durvalumab in Adult Participants With Solid Tumours
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 40
- 试验地点
- 24
- 主要终点
- Area under the concentration-time curve
研究概览
简要总结
The purpose of the study is to determine a subcutaneous (SC: under the skin) durvalumab + recombinant human hyaluronidase (rHu) dose that yields systemic drug exposure similar to intravenous (IV: into the veins) durvalumab administration and to evaluate the pharmacokinetics and safety of SC durvalumab + rHu injection in participants with different types of solid tumours (cancers).
详细描述
This is a Phase I, multicentre study that will consist of 2 parts -
- Part 1: Dose Escalation
- Part 2: Dose Expansion
Part 1 may include participants with solid tumours - non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC) or limited-stage small cell lung cancer (LS-SCLC). It will further consist of 2 planned dose levels of SC durvalumab - Dose level 1 (DL1) and Dose level 2 (DL2).
Part 2 will include participants with unresectable HCC. It will be initiated once a dose has been identified based on Part 1.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- All
- 接受健康志愿者
- 否
入选标准
- •An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Life expectancy of ≥ 12 weeks at enrolment.
- •Adequate organ and marrow function.
- •Minimum body weight > 30 kg.
- •Part 1 only:
- •Locally Advanced Unresectable (Stage III) NSCLC Participants -
- •Histological or cytological documented evidence of NSCLC (locally advanced, unresectable, Stage III).
- •Must have received at least 2 cycles of platinum-based chemotherapy concurrent with definitive radiation therapy.
- •Have not progressed following definitive concurrent chemoradiation.
- •LS-SCLC Participants -
- •Histologically or cytologically documented LS-SCLC (Stage I-III).
- •Received 4 cycles of chemotherapy concurrent with radiotherapy, which must be completed within 1 to 42 days prior to enrolment.
- •Have not progressed following definitive concurrent chemoradiation.
- •Part 1 and 2:
- •Unresectable HCC Participants -
- •Unresectable HCC based on histopathological confirmation.
- •No prior systemic therapy for unresectable HCC.
- •Must not be eligible for locoregional therapy for unresectable HCC.
- •Child-Pugh Score class A.
- •Measurable disease as defined by RECIST v1.1.
排除标准
- •Active or prior documented autoimmune disease requiring systemic treatment.
- •Uncontrolled infection (including human immunodeficiency virus [HIV], hepatitis B or C).
- •Prior exposure to immune checkpoint inhibitors.
- •Part 1 only:
- •Locally Advanced Unresectable (Stage III) NSCLC Participants -
- •Mixed SCLC and NSCLC histology.
- •Active pneumonitis or interstitial lung disease requiring systemic therapy.
- •LS SCLC Participants -
- •Mixed SCLC and NSCLC histology.
- •Extensive-stage disease.
- •History of Grade ≥ 2 pneumonitis.
- •Part 1 and 2:
- •Unresectable HCC Participants -
- •Hepatic encephalopathy.
- •Uncontrolled ascites.
- •Active gastrointestinal (GI) bleeding.
研究组 & 干预措施
Part 1: SC Durvalumab DL2
Participants will receive DL2 of SC durvalumab + rHu followed by IV durvalumab at predefined intervals.
干预措施: IV durvalumab (Drug)
Part 1: SC Durvalumab DL2
Participants will receive DL2 of SC durvalumab + rHu followed by IV durvalumab at predefined intervals.
干预措施: SC durvalumab + rHu (Drug)
Part 1: SC Durvalumab DL1
Participants will receive DL1 of SC durvalumab + rHu followed by IV durvalumab at predefined intervals.
干预措施: SC durvalumab + rHu (Drug)
Part 1: SC Durvalumab DL1
Participants will receive DL1 of SC durvalumab + rHu followed by IV durvalumab at predefined intervals.
干预措施: IV durvalumab (Drug)
Part 2: Expansion Cohort, SC Durvalumab Dose Level X
Participants will receive dose level X (determined from data analysis in Part 1) of SC durvalumab + rHu followed by IV durvalumab at predefined intervals.
干预措施: SC durvalumab + rHu (Drug)
Part 2: Expansion Cohort, SC Durvalumab Dose Level X
Participants will receive dose level X (determined from data analysis in Part 1) of SC durvalumab + rHu followed by IV durvalumab at predefined intervals.
干预措施: IV durvalumab (Drug)
Part 1: SC Durvalumab DL1
Participants will receive DL1 of SC durvalumab + rHu followed by IV durvalumab at predefined intervals.
干预措施: Tremelimumab (Drug)
Part 2: Expansion Cohort, SC Durvalumab Dose Level X
Participants will receive dose level X (determined from data analysis in Part 1) of SC durvalumab + rHu followed by IV durvalumab at predefined intervals.
干预措施: Tremelimumab (Drug)
Part 1: SC Durvalumab DL2
Participants will receive DL2 of SC durvalumab + rHu followed by IV durvalumab at predefined intervals.
干预措施: Tremelimumab (Drug)
结局指标
主要结局
Area under the concentration-time curve
时间窗: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
To characterise the AUC of SC durvalumab.
Observed lowest concentration before the next dose is administered (Ctrough)
时间窗: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
To characterise the Ctrough of SC durvalumab
次要结局
- Area under the concentration-time curve from time 0 to last quantifiable concentration (AUClast)(From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).)
- Maximum observed concentration (Cmax)(From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).)
- Time to reach maximum concentration following drug administration (tmax)(From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).)
- Terminal elimination half-life (t1/2λz)(From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).)
- Total body clearance/apparent total body clearance (CL[/F])(From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).)
- Apparent volume of distribution based on the terminal phase volume (Vz[/F])(From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).)
- Average drug concentration over a dosing interval (Cavg)(From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).)
- Serum concentration of durvalumab(From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).)
- Number of participants with adverse events (AEs)(Up to Survival Follow-up (approximately 17 months))
- Number of participants with dose-limiting toxicities (DLTs)(Up to Survival Follow-up (approximately 17 months))