2024-516698-56-00招募中2 期
A Modular Phase I/II Open-label Dose Escalation and Dose Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of AZD9793, a T cell-engaging Antibody Targeting Glypican-3 (GPC3) in Adult Participants with Advanced or Metastatic Solid Tumours (RHEA-1)
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- AEs leading to discontinuation of AZD9793
研究概览
简要总结
To investigate the safety and tolerability, and determine the Maximum Tolerated Dose (MTD), Optimal Biological Dose (OBD), and/or Recommended Dose(s) for Expansion (RDEs), as well as the Recommended Phase 2 Dose(s) (RP2Ds), of AZD9793 monotherapy, and to evaluate its preliminary anti‑tumour activity in participants with advanced or metastatic solid tumours with GPC3 expression
研究设计
- 分配方式
- Na
- 主要目的
- Follow-up period and Survival follow-up period
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 at the time of signing the informed consent
- •Child-Pugh Score class A.
- •Previous therapy: Part A: Patients who have received at least one prior line of standard systemic therapy for HCC as per NCCN or other local scientific guidelines and for which a clinical study is the best option for next treatment based on prior response and/or tolerability and/or patient/investigator decision.
- •Previous therapy: Part B: Patients must not have received more than 1 prior line of systemic therapy in the advanced recurrent and/or metastatic setting.
- •GPC3 positive tumour as determined by a central laboratory using an analytically validated IHC assay. Patients who previously received any therapy targeting GPC3 must undergo central laboratory GPC3 testing on tumour tissue collected after completion of the prior GPC3‑targeted therapy
- •Must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- •Eastern Cooperative Oncology Group Performance status (ECOG PS): 0-1 at screening
- •Predicted life expectancy of ≥ 12 weeks.
- •Adequate organ and bone marrow function measured within 28 days prior to first dose as defined by the protocol.
- •Contraceptive use by men or women should be consistent with local regulations, as defined by the protocol.
- •Confirmed advanced recurrent and/or metastatic and/or unresectable HCC, which is histopathologically proven based on the criteria established by the World Health Organization.
- •Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional therapy) or stage C.
排除标准
- •Unresolved toxicity from prior anticancer therapy, including irAEs, of Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 2 except for vitiligo, peripheral neuropathy related to prior anti-cancer therapy, alopecia, endocrine disorders that are controlled with replacement hormone therapy and asymptomatic laboratory abnormalities.
- •Cardiac conditions as defined by the protocol.
- •History of thromboembolic event within the past 3 months prior to the scheduled first dose of study intervention
- •Central nervous system (CNS) pathology or symptomatic or clinically unstable CNS metastases, as defined by the protocol, within 3 months prior to consent.
- •Infectious disease including active human immunodeficiency virus (HIV), and uncontrolled active systemic fungal, bacterial or other infection.
- •Prior to enrolment, participation in another clinical study with an investigational product administered in the last 21 days or 5 half-lives whichever is shorter.
- •CAR-T cell therapy within the last 6 months prior to enrolment on this study.
- •Known allergy or hypersensitivity to AZD9793 or any of the excipients of the product as outlined in the IB.
- •Requires chronic immunosuppressive therapy (including steroids > 10 mg prednisone/day or equivalent)
- •Received radiation within 14 days prior to first dose of study treatment; palliative radiation to reduce the risk of tumour lysis syndrome (TLS) or CRS/neurotoxicity in participants with bulky disease is permitted
- •Undergone a major surgical procedure within 14 days to allow adequate healing
- •Experienced unacceptable cytokine release syndrome (CRS) or Immune Effector Cell Associated Neurotoxicity (ICANS) following prior T cell engagers (TCE) or chimeric antigen receptor T (CAR-T) cell therapy.
- •Known fibrolamellar HCC, sarcomatoid HCC, or combined hepatocellular malignant cholangiocarcinoma
- •Previous history of hemophagocytic lymphohistiocytosis (HLH) / macrophage activation syndrome (MAS).
- •Active or prior documented autoimmune or inflammatory disorders within 3 years of start of treatment.
研究组 & 干预措施
AZD9793
Test
干预措施: AZD9793 (Drug)
结局指标
主要结局
AEs leading to discontinuation of AZD9793
AEs leading to discontinuation of AZD9793
Assess clinically significant alterations in vital signs and abnormal laboratory parameters
Assess clinically significant alterations in vital signs and abnormal laboratory parameters
Incidence of DLTs (only for Dose Escalation).
Incidence of DLTs (only for Dose Escalation).
Incidence of AEs, SAEs, and AESIs.
Incidence of AEs, SAEs, and AESIs.
Objective Response Rate (ORR) (For dose expansion only)
Objective Response Rate (ORR) (For dose expansion only)
次要结局
- Number and percentage of participants who develop anti-drug antibodies (ADAs) measured in serum
- Change in target lesion (TL) tumour size
- CD8+ T cell infiltration in tumours pre- and post- treatment measured by immunohistochemistry
- Objective Response Rate (ORR) (For dose escalation only)
- Best overall response (BOR)
- Disease Control Rate (DCR) at 12 weeks
- Durable response rate (DRR)
- Duration of response (DoR)
- Time To Response (TTR)
- % change in tumour size
- Progression free Survival (PFS)
- Overall Survival (OS) [Dose expansion only]
- Pharmacokinetics of AZD9793: Maximum serum concentration of the study drug (Cmax), serum concentrations of AZD9793, Area Under the concentration-time curve (AUC), Clearance, Terminal elimination half-life (t1/2)
- Number and percentage of participants who develop ADAs, measured in serum
- CD8+ T cell infiltration in tumours pre- and post- treatment
研究者
AstraZeneca Clinical Study Information Center
Scientific
AstraZeneca AB
研究点 (2)
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