Overview
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.
Eligibility
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.