Study of XL092 in Combination With Immuno-Oncology Agents in Subjects With Solid Tumors

Inclusion Criteria:

   - Cytologically or histologically confirmed solid tumor that is unresectable, locally
   advanced or metastatic.

   - Dose-Escalation Cohorts: Subjects with a solid tumor that is unresectable or
   metastatic and for which life-prolonging therapies do not exist or available therapies
   are intolerable or no longer effective.

   - Expansion Cohort 1 (ccRCC): Subjects with unresectable advanced or metastatic RCC with
   a clear cell component who have not received prior systemic therapy.

      - Note: Prior non-VEGF targeted adjuvant or neoadjuvant is allowed if disease
      recurrence occurred 6 months after the last dose.

   - Expansion Cohort 2 (ccRCC): Subjects with unresectable advanced or metastatic RCC with
   a clear cell component.

      - Must have radiographically progressed after a combination therapy consisting of a
      PD-1/PD-L1 targeting mAb with a VEGFR-TKI or a PD-1 targeting mAb with a CTLA-4
      mAb as the preceding line of therapy.

      - Must have received no more than one prior systemic anticancer therapy for
      unresectable advanced or metastatic renal cell carcinoma.

   - Expansion Cohort 3 (mCRPC): Men with metastatic adenocarcinoma of the prostate.

      - Must have progressed during or after one NHT given for castration-sensitive
      locally advanced (T3 or T4) or metastatic castration-sensitive prostate cancer
      (CSPC), M0 CRPC, or mCRPC.

   - Expansion Cohort 4 (UC, ICI-naive): Subjects with histologically confirmed
   unresectable, locally advanced or metastatic transitional cell carcinoma of the
   urothelium (including the renal pelvis, ureter, urinary bladder, or urethra).

      - Must have progressed during or after prior first-line platinum-based combination
      therapy, including subjects who received prior neoadjuvant or adjuvant
      platinum-containing therapy with disease recurrence < 12 months from the end of
      last therapy.

      - Must have received no more than 1 prior line of systemic anticancer therapy for
      unresectable, locally advanced or metastatic disease.

   - Expansion Cohort 5 (UC, ICI-experienced): Subjects with histologically confirmed
   unresectable, locally advanced or metastatic transitional cell carcinoma of the
   urothelium (including the renal pelvis, ureter, urinary bladder, or urethra).

      - Must have progressed during or after prior PD-1/PD-L1 targeting ICI therapy given
      as monotherapy, combination therapy, maintenance therapy or adjuvant therapy.

      - Must have received no more than 2 prior lines of systemic anticancer therapy for
      unresectable advanced or metastatic disease.

   - Expansion Cohort 6 (nccRCC): Subjects with unresectable advanced or metastatic nccRCC
   of the following subtypes: Papillary RCC (any type), unclassified RCC, and
   translocation-associated. Among the eligible histologic subtypes, sarcomatoid features
   are allowed.

      - No prior systemic anticancer therapy is allowed except adjuvant or neoadjuvant
      therapy if disease recurrence occurred at least 6 months after the last dose.

   - Expansion Cohort 7 (HCC): Subjects with inoperable locally advanced, recurrent, or
   metastatic HCC that is not amenable to curative treatment or locoregional therapy.

   - Expansion Cohort 8 (NSCLC): Subjects with Stage IV non-squamous NSCLC with positive
   PD-L1 expression (tumor proportion score [TPS] 1-49%) and without prior systemic
   anticancer therapy for metastatic disease.

   - Expansion Cohort 9 (NSCLC): Subjects with Stage IV non-squamous NSCLC who have
   radiologically progressed following treatment with one prior immune checkpoint
   inhibitor (anti-PD-1 or anti-PD-L1) for metastatic disease.

   - Expansion Cohort 10 (CRC): Subjects with histologically confirmed unresectable,
   locally advanced, or metastatic adenocarcinoma of the colon or rectum.

   - Expansion Cohort 11 (HNSCC): Subject with inoperable, refractory, recurrent or
   metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, and larynx. PD-L1
   combined positive score (CPS) ≥1.

   - For all Expansion Cohorts except Cohort 3: Measurable disease per RECIST 1.1 as
   determined by the Investigator.

   - For expansion cohorts only: Archival tumor tissue material, if available, or fresh
   tumor tissue if it can be safely obtained.

   - Recovery to baseline or ≤ Grade 1 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%.

   - Adequate organ and marrow function.

   - 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:

   - For all Dose-Escalation cohorts: Prior treatment with XL092. For all Expansion
   Cohorts: Prior treatment with XL092, nivolumab, ipilimumab or relatlimab with the
   following exceptions: Prior PD-1/PD-L1, LAG-3 and CTLA-4 targeting therapy for locally
   advanced or metastatic disease is allowed for Cohort 2 (ccRCC), Cohort 5 (UC), Cohort
   9 (NSCLC).

   - For all Dose-Escalation Cohorts and Expansion Cohort 2 (ccRCC), 3 (mCRPC), Cohort 5
   (UC), Cohort 9 (NSCLC) and Cohort 10 (CRC): Receipt of any type of small molecule
   kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before
   first dose of study treatment.

   - For Cohort 3 (mCRPC): Receipt of abiraterone within 1 week; cyproterone within 10
   days; or receipt of flutamide, nilutamide, bicalutamide, enzalutamide, or other
   androgen receptor inhibitors within 2 weeks before first dose of study treatment.

   - For all Dose-Escalation Cohorts and Expansion Cohort 2 (ccRCC), Cohort 3 (mCRPC),
   Cohort 5 (UC), Cohort 9 (NSCLC) and Cohort 10 (CRC): Receipt of any type of anticancer
   antibody or systemic chemotherapy within 4 weeks before first dose of study treatment.

   - Any complementary medications (eg, herbal supplements or traditional Chinese
   medicines) to treat the disease under study within 2 weeks before first dose of study
   treatment.

   - Prior external radiation therapy for bone metastasis within 2 weeks, for other tumor
   sites within 4 weeks, and prior radium-223 therapy within 6 weeks before first dose of
   study treatment, unless otherwise specified.

   - 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 first dose of study treatment.

   - Concomitant anticoagulation with oral anticoagulants and platelet inhibitors.

   - Administration of a live, attenuated vaccine within 30 days prior to enrollment.

   - Uncontrolled, significant intercurrent or recent illness.

   - Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per
   electrocardiogram (ECG) within 14 days before first dose of study treatment.

   - Subjects with inadequately treated adrenal insufficiency.

   - Pregnant or lactating females.

   - Any other active malignancy within two years before first dose of study treatment,
   except for locally curable cancers that have been apparently cured such as basal or
   squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the
   prostate, cervix, or breast.

   - For Cohort 2 (ccRCC, 2L): Receipt of a prior triplet therapy including a VEGFR-TKI, a
   PD1 targeting mAb, and a CTLA-4 mAb.

   - For Cohort 3 (mCRPC): Receipt of a taxane-based chemotherapy for mCRPC.

   - For Cohort 4 (UC, ICI-naïve): Subjects who have had recurrence within the 6 months of
   completing adjuvant anti-PD-(L)1 treatment.

   - For Cohort 6 (nccRCC, 1L): Subjects with chromophobe, renal medullary carcinoma, or
   pure collecting duct nccRCC.

   - For Cohort 7 (HCC):

      - Documented hepatic encephalopathy (HE) within 6 months before randomization (see
      Section 6.5.2 for a case definition of HE).

      - Clinically meaningful ascites (ie, ascites requiring paracentesis or escalation
      in diuretics) within 6 months before randomization.

      - Subjects who have received any local anticancer therapy including surgery, PEI,
      RFA, MWA, transarterial chemoembolization (TACE), or transarterial
      radioembolization (TARE) within 28 days prior to randomization.

      - Subjects with known fibrolamellar carcinoma, sarcomatoid HCC, or mixed
      hepatocellular cholangiocarcinoma

   - For Cohort 10 (CRC, 2L+): Receipt of prior therapy with regorafenib and/or TAS-102.

   - For Cohort 11 (HNSCC): Primary tumor site of the nasopharyngeal area.

   - For Cohorts 1 (ccRCC, 1L), 2 (ccRCC, 2L), 4, 5 (UC), 7 (HCC), 8 (NSCLC 1L PD-L1 low),
   9 (NSCLC, 2L+), 10 (CRC, MSS, 2L+), and 11 (HNSCC):

      - Troponin T (TnT) or I (TnI) > 2 × institutional ULN.

Note: Additional Inclusion and Exclusion criteria may apply.