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

Inclusion Criteria:

• Histologically confirmed nccRCC that is unresectable, advanced or metastatic.Histologic subtypes including papillary, unclassified, and translocation-associatedare allowed. Among the eligible histologic subtypes, sarcomatoid features areallowed.

• 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 priortreatments unless AE(s) are deemed clinically nonsignificant by the Investigatorand/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 highlyeffective 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 subtypesof nccRCC.

• Prior systemic anticancer therapy for unresectable locally advanced or metastaticnccRCC including investigational agents.

• Note: One prior systemic adjuvant therapy, including immune checkpointinhibitor therapy and excluding sunitinib, is allowed for completely resectedRCC and if recurrence occurred at least 6 months after the last dose ofadjuvant therapy.

• Radiation therapy for bone metastases within 2 weeks, any other radiation therapywithin 4 weeks prior to randomization.

• Known brain metastases or cranial epidural disease unless adequately treated withradiotherapy (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 betransitioned to LMWH prior to randomization. Subjects who require treatment withplatelet inhibitors are not eligible.

• Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeksprior to randomization. Prior laparoscopic nephrectomy within 4 weeks prior torandomization. Minor surgery (eg, simple excision, tooth extraction) within 10 daysbefore randomization. Complete wound healing from major or minor surgery must haveoccurred at least prior to randomization.

• Note: Fresh tumor biopsies should be performed at least 7 days beforerandomization. Subjects with clinically relevant ongoing complications fromprior surgical procedures, including biopsies, are not eligible.

• Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms perelectrocardiogram (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 beadministered at least 2 weeks before randomization.