Study of XL092 + Nivolumab vs Sunitinib in Subjects With Advanced or Metastatic Non-Clear Cell Renal Cell Carcinoma

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized Open-Label Phase 3 Study of XL092 + Nivolumab vs Sunitinib in Subjects With Advanced or Metastatic Non-Clear Cell Renal Cell Carcinoma

Conditions
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Non-Clear Cell Renal Cell Carcinoma

Intervention / Treatment
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* Drug: XL092
* Drug: Nivolumab
* Drug: Sunitinib Malate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XL092 + Nivolumab<br>Subjects with advanced or metastatic nccRCC will receive XL092 + nivolumab | Drug: XL092<br>* Specified doses on specified days<br>Drug: Nivolumab<br>* Specified doses on specified days<br>* Other names: Opdivo®;|
| Active Comparator: Sunitinib Malate<br>Subjects with advanced or metastatic nccRCC will receive an active comparator of sunitinib | Drug: Sunitinib Malate<br>* Specified doses on specified days<br>* Other names: Sutent®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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 | Approximately 27 months after the first subject is randomized | 
| Objective response rate (ORR) as assessed by BIRC per RECIST 1.1 | 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 | Up to 24 months after the first subject is randomized | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Overall Survival (OS) | Defined as the time from randomization to death due to any cause | Approximately 46 months after the first subject is randomized |