A Phase 1b/2 Dose-finding and Expansion Study Evaluating the Safety and Efficacy of Zanzalintinib (XL092) Combined With Either AB521 or AB521 Plus Nivolumab in Subjects With Advanced Clear Cell Renal Cell Carcinoma or Other Advanced Solid Tumors.
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Exelixis
- 入组人数
- 140
- 试验地点
- 14
- 主要终点
- Dose-finding Stage: Number of participants with dose-limiting toxicities (DLTs)
研究概览
简要总结
The goal of this clinical trial is to learn about the safety and preliminary antitumor activity of zanzalintinib in combination with AB521 (doublet) and in combination with AB521 plus nivolumab (triplet) in participants with advanced ccRCC or other advanced solid tumors. The main questions it aims to answer are:
- The recommended doses (RDs)
- The safety and tolerability
- The PK and the preliminary efficacy
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
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with a).unresectable advanced or metastatic solid tumor; b). unresectable advanced or metastatic clear cell renal cell carcinoma and no prior anticancer therapy; or c). unresectable advanced or metastatic clear cell renal cell carcinoma and has received at least one prior anticancer therapy.
- •Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1; Eisenhauer et al, 2009) as determined by the Investigator.
- •For all participants, archival tumor tissue material should be obtained; if archival tissue is not available or is older than 2 years, then a fresh biopsy should be obtained, if medically feasible. Specific requirements for tumor tissue samples will be described in the Laboratory Manual.
- •Recovery to baseline or ≤ Grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) v5 from AE(s) related to any prior treatments unless AE(s) are deemed clinically nonsignificant by the Investigator and/or stable on supportive therapy.
- •Karnofsky Performance Status (KPS) ≥70%.
- •Screening ambulatory oxygen saturation (SpO2) ≥92%.
- •Screening left ventricular ejection fraction (LVEF) above the institutional lower limit of normal.
排除标准
- •Participants who have been previously treated with a HIF-2α targeted therapy and/or zanzalintinib.
- •Radiation therapy for bone metastases within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Participants with clinically-relevant ongoing complications from prior radiation therapy are not eligible.
- •Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment.
- •Concomitant anticoagulation with oral anticoagulants except for a). prophylactic use of low-dose aspirin for cardioprotection or low dose low molecular weight heparins (LMWH) or b). therapeutic doses of LMWH or specified direct factor Xa inhibitors.
- •Administration of a live, attenuated vaccine within 30 days prior to enrollment.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Dose-finding Cohort A: Zanzalintinib + AB521
Participants with solid tumors will receive zanzalintinib + AB521
干预措施: zanzalintinib (Drug)
Dose-finding Cohort A: Zanzalintinib + AB521
Participants with solid tumors will receive zanzalintinib + AB521
干预措施: AB521 (Drug)
Dose-finding Cohort B: zanzalintinib + AB521 + nivolumab
Participants with ccRCC will receive zanzalintinib + AB521 + nivolumab
干预措施: zanzalintinib (Drug)
Dose-finding Cohort B: zanzalintinib + AB521 + nivolumab
Participants with ccRCC will receive zanzalintinib + AB521 + nivolumab
干预措施: AB521 (Drug)
Dose-finding Cohort B: zanzalintinib + AB521 + nivolumab
Participants with ccRCC will receive zanzalintinib + AB521 + nivolumab
干预措施: Nivolumab (Biological)
Expansion Cohort 1: Zanzalintinib + AB521
Participants with ccRCC will receive zanzalintinib + AB521
干预措施: zanzalintinib (Drug)
Expansion Cohort 1: Zanzalintinib + AB521
Participants with ccRCC will receive zanzalintinib + AB521
干预措施: AB521 (Drug)
Expansion Cohort 2: zanzalintinib + AB521 + nivolumab
Participants with ccRCC will receive zanzalintinib + AB521 + nivolumab
干预措施: zanzalintinib (Drug)
Expansion Cohort 2: zanzalintinib + AB521 + nivolumab
Participants with ccRCC will receive zanzalintinib + AB521 + nivolumab
干预措施: AB521 (Drug)
Expansion Cohort 2: zanzalintinib + AB521 + nivolumab
Participants with ccRCC will receive zanzalintinib + AB521 + nivolumab
干预措施: Nivolumab (Biological)
结局指标
主要结局
Dose-finding Stage: Number of participants with dose-limiting toxicities (DLTs)
时间窗: Up to 24 months
Expansion Stage: Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by the Investigator
时间窗: Up to 24 months
次要结局
- Dose-finding Stage: Number of participants with adverse events (AEs), including serious adverse events (SAEs) and immune-mediated adverse events (imAEs)(Up to 24 months)
- Dose-finding Stage: Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by the Investigator(Up to 24 months)
- Expansion Stage: Number of participants with adverse events (AEs), including serious adverse events (SAEs), and immune-mediated adverse events (imAEs)(Up to 24 months)
- Dose-finding Stage: Concentration of study treatments (zanzalintinib and AB521) in plasma at specified time points(Up to 24 months)
- Expansion Stage: Duration of response (DOR) per RECIST 1.1 as assessed by the Investigator(Up to 24 months)
- Expansion Stage: Progression-free survival (PFS) per RECIST 1.1 as assessed by the Investigator(Up to 24 months)
- Expansion Stage: Overall survival (OS)(Up to 24 months)
- Expansion Stage: Concentration of study treatments (zanzalintinib and AB521) in plasma at specified time points(Up to 24 months)