A Randomized Open-Label Phase 3 Study of XL092 + Nivolumab vs Sunitinib in Subjects With Advanced or Metastatic Non-Clear Cell Renal Cell Carcinoma
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Exelixis
- 入组人数
- 317
- 试验地点
- 324
- 主要终点
- Duration of Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), by Blinded Independent Radiology Committee (BIRC)
研究概览
简要总结
This is a multicenter, randomized (2:1), open-label, controlled Phase 3 trial of XL092 in combination with nivolumab versus sunitinib in subjects with unresectable, locally advanced or metastatic nccRCC who have not received prior systemic anticancer therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Histologically confirmed nccRCC that is unresectable, advanced or metastatic. Histologic subtypes including papillary, unclassified, and translocation-associated are allowed. Among the eligible histologic subtypes, sarcomatoid features are allowed.
- •Measurable disease according to RECIST v1.1 as determined by the Investigator.
- •Available archival tumor biopsy material.
- •Recovery to baseline or ≤ Grade 1 per 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.
- •Age 18 years or older on the day of consent.
- •Karnofsky Performance Status (KPS) ≥ 70%.
- •Adequate organ and marrow function within 14 days prior to randomization.
- •Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception.
- •Female subjects of childbearing potential must not be pregnant at screening.
排除标准
- •Chromophobe, renal medullary carcinoma, and pure collecting duct histologic subtypes of nccRCC.
- •Prior systemic anticancer therapy for unresectable locally advanced or metastatic nccRCC including investigational agents.
- •Note: One prior systemic adjuvant therapy, including immune checkpoint inhibitor therapy and excluding sunitinib, is allowed for completely resected RCC and if recurrence occurred at least 6 months after the last dose of adjuvant therapy.
- •Radiation therapy for bone metastases within 2 weeks, any other radiation therapy within 4 weeks prior to randomization.
- •Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy (including radiosurgery) or surgically removed and stable for at least 4 weeks before randomization.
- •Concomitant anticoagulation with oral anticoagulants and platelet inhibitors. Subjects who are receiving oral anticoagulants at the time of screening must be transitioned to LMWH prior to randomization. Subjects who require treatment with platelet inhibitors are not eligible.
- •Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks prior to randomization. Prior laparoscopic nephrectomy within 4 weeks prior to randomization. Minor surgery (eg, simple excision, tooth extraction) within 10 days before randomization. Complete wound healing from major or minor surgery must have occurred at least prior to randomization.
- •Note: Fresh tumor biopsies should be performed at least 7 days before randomization. Subjects with clinically relevant ongoing complications from prior surgical procedures, including biopsies, are not eligible.
- •Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per electrocardiogram (ECG) within 14 days before randomization.
- •Pregnant or lactating females.
- •Administration of a live, attenuated vaccine within 30 days before randomization.
- •Note: If feasible, approved non-live vaccines for SARS-CoV-2 should be administered at least 2 weeks before randomization.
研究组 & 干预措施
XL092 + Nivolumab
Subjects with advanced or metastatic nccRCC will receive XL092 + nivolumab
干预措施: XL092 (Drug)
Sunitinib Malate
Subjects with advanced or metastatic nccRCC will receive an active comparator of sunitinib
干预措施: Sunitinib Malate (Drug)
XL092 + Nivolumab
Subjects with advanced or metastatic nccRCC will receive XL092 + nivolumab
干预措施: Nivolumab (Drug)
结局指标
主要结局
Duration of Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), by Blinded Independent Radiology Committee (BIRC)
时间窗: Approximately 27 months after the first subject is randomized
Defined as the time from randomization to the earlier of either radiographic PD per RECIST 1.1 as determined by the BIRC or death from any cause
Objective response rate (ORR) as assessed by BIRC per RECIST 1.1
时间窗: Up to 24 months after the first subject is randomized
Defined as the proportion of subjects with the best overall response of complete response (CR) or partial response (PR) per RECIST 1.1 as determined by the BIRC that is confirmed at a follow-up assessment ≥ 28 days later
次要结局
- Duration of Overall Survival (OS)(Approximately 46 months after the first subject is randomized)