A Dose-Escalation and Expansion Study of the Safety and Pharmacokinetics of XL092 as Single-Agent and Combination Therapy in Subjects with Inoperable Locally Advanced or Metastatic Solid Tumors

This is a Phase 1, open-label, dose-escalation and expansion study, evaluating the safety,
tolerability, pharmacokinetics (PK), preliminary antitumor activity, and effect on biomarkers
of XL092 administered alone, in combination with atezolizumab, and in combination with
avelumab to subjects with advanced solid tumors.

Inclusion Criteria:

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

- Dose-escalation (single-agent and combination therapy): 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 A (ccRCC): Subjects with previously treated advanced RCC with clear
cell histology (including those with a sarcomatoid component) who have
radiographically progressed following treatment with at least one prior systemic
anticancer regimen for inoperable locally advanced or metastatic disease.

- Expansion Cohorts B and E (nccRCC): Subjects with previously treated advanced RCC with
non-clear cell histology who have radiographically progressed following treatment with
at least one prior systemic anticancer regimen for inoperable locally advanced or
metastatic disease.

- Expansion Cohorts C and F (HR+ BC): Subjects with breast cancer that is hormone
receptor positive (ER+ and/or PR+) and negative for human epidermal growth factor
receptor 2 (HER-2) and who have radiographically progressed during or following
treatment with at least one prior systemic anticancer regimen for inoperable locally
advanced or metastatic disease.

- Expansion Cohorts D and G (mCRPC): Subjects with metastatic CRPC (adenocarcinoma of
the prostate). Neuroendocrine differentiation and other features permitted if
adenocarcinoma is the primary histology.

- Expansion Cohort H (CRC): Subjects with histologically confirmed unresectable, locally
advanced, or metastatic adenocarcinoma of the colon or rectum, KRAS/NRAS wild-type
(confirmed via local testing report) and determined NOT to have microsatellite
instability high (MSI-high) or mismatch repair deficient (dMMR) by local testing, who
received the following standard of care chemotherapy regimens as prior therapy for
metastatic CRC:

- Fluoropyrimidine, irinotecan and oxaliplatin, with or without an anti-VEGF
monoclonal antibody (bevacizumab)

- Anti-EGFR monoclonal antibody (cetuximab or panitumumab)

- BRAF inhibitor (in combination with cetuximab +/- binimetinib) for subjects with
BRAF V600E mutations

- Expansion Cohorts: Subjects must have measurable disease per RECIST 1.1.

- Tumor tissue material:

- Subjects in the non-biomarker cohort provide archival, if available, or fresh
tumor tissue if it can be safely obtained.

- Recovery to baseline or ≤ Grade 1 severity (CTCAE v5) from adverse events (AEs),
including immune-related adverse events (irAEs), related to any prior treatments,
unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.

- 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:

- Prior treatment with XL092 (all cohorts), prior treatment with PD-L1/PD-1 targeting
immune checkpoint inhibitor (Cohorts E, F, G, and H only), or prior treatment with
regorafenib and/or TAS-102 (Cohort H only).

- Receipt of any type of small molecule kinase inhibitor within 2 weeks before first
dose of study treatment.

- Receipt of any type of anticancer antibody, systemic chemotherapy, or hormonal
anticancer therapy within 4 weeks before first dose of study treatment.

- Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy
within 4 weeks before first dose of study treatment. Subjects with clinically relevant
ongoing complications from prior radiation therapy are not eligible.

- Known brain metastases or cranial epidural disease unless adequately treated with
radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks
before first dose of study treatment.

- Uncontrolled, significant intercurrent or recent illness.

- Concomitant use of certain medications.

- Corrected QT interval calculated by the Fridericia formula (QTcF) > 450 ms for males
and > 470 ms for females. Single ECGs are no longer permitted.

- Pregnant or lactating females.

- Diagnosis of another malignancy within 2 years before first dose of study treatment,
except for superficial skin cancers, or localized, low grade tumors deemed cured and
not treated with systemic therapy.

Additional Exclusion Criteria for XL092 + Atezolizumab Combination Therapy Cohorts ONLY:

- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other
form of immunosuppressive therapy within 2 weeks prior to first dose of study
treatment.

- Administration of a live, attenuated vaccine within 30 days before first dose of study
treatment.

Additional Exclusion Criteria for XL092 + Avelumab Combination Therapy Cohorts ONLY:

- Active autoimmune disease that might deteriorate when receiving an immunostimulatory
agent.

- Administration of a live, attenuated vaccine within 30 days before first dose of study
treatment.