STELLAR-001

Inclusiecriteria: U mag meedoen als

• Cytologically or histologically confirmed solid tumor that is inoperable locally advanced, metastatic, or recurrent:
- Dose-Escalation Stages (single-agent and combination therapy):
a. Subjects with unresectable or metastatic solid tumor for which life-prolonging therapies do not exist or available
therapies are intolerable or no longer effective
- Cohort-Expansion Stages (single-agent and combination therapy):
b. Expansion Cohort A: Subjects with previously treated ccRCC who have progressed after systemic anticancer treatment
c. Expansion Cohorts B and E: Subjects with previously treated advanced nccRCC who have progressed after systemic anticancer treatment
d. Expansion Cohorts C and F: Subjects with HR+ BC who have progressed on or after systemic anticancer treatment
e. Expansion Cohorts D and G: Subjects with mCRPC. Neuroendocrine differentiation and other features permitted if adenocarcinoma is primary histology
f. Expansion Cohort H: Subjects with histologically confirmed unresectable, locally advanced, or metastatic CRC
g. Expansion Cohort I: Subjects with UC (including renal pelvis, ureter, urinary bladder, or urethra) who received first-line chemotherapy of gemcitabine + cisplatin and/or gemcitabine + carboplatin
h. Expansion Cohort J: Subjects with UC (including renal pelvis, ureter, urinary bladder, or urethra) who progressed on or after PD-1/PD-L1 targeting ICI therapy
i. Expansion Cohort K: Subjects with UC (including renal pelvis, ureter, urinary bladder, or urethra) who progressed on or after first-line platinum-based combination therapy
• Expansion Cohorts only: measurable disease per RECIST 1.1 as determined by the investigator. Inclusion requirement does not apply for Cohort I (UC, Maintenance Therapy)
• Tumor tissue material (non-biomarker cohort - provide archival, if available, or fresh tumor tissue if it can be safely obtained; biomarker cohorts -provide fresh tumor and skin biopsies)
• Recovery to baseline or ≤ Grade 1 severity (CTCAE v5) from AEs, including irAEs, related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy
• Age 18 years or older on the day of consent
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
• Adequate organ and marrow function
• Capable of understanding and complying with the protocol requirements and must have signed the informed consent document
• Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception (defined in Appendix L of the protocol)
• Female subjects of childbearing potential must not be pregnant at screening

Exclusiecriteria: U mag niet meedoen als

• Prior treatment with XL092 (all cohorts), prior treatment with PD-L1/PD-1 targeting immune checkpoint inhibitor (Cohorts E, F, G, H, I, and K only) or prior avelumab (Cohort J 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 Metastase Meer informatie over de term "Metastase" Metastase (of uitzaaiing) is de verspreiding van tumorcellen vanuit de oorspronkelijke locatie (de primaire locatie) naar een ander deel van het lichaam. Tumoren kunnen metastaseren (uitzaaien) door nabijgelegen weefsel binnen te dringen of door zich te verspreiden via de circulatie (bloed en lymfestelsel). s or cranial epidural disease unless adequately treated with radiotherapy and/or surgery and stable for at least 4 weeks before first dose of study treatment
• Concomitant anticoagulation with oral anticoagulants and platelet inhibitors
• Use of a strong P450 CYP3A4 inhibitor or inducer within 5 half-lives prior to first dose of study treatment
• Use of a sensitive substrate of CYP3A4, CYP2C19, CYP2C9, or CYP2C8 within 5 half-lives prior to first dose of study treatment
• Use of a sensitive substrate of P-gp or BCRP transporter within 5 half-lives prior to first dose of study treatment
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to an active infection requiring systemic treatment; acute or chronic hepatitis B or C infection, HIV, or AIDS-related illness; positive test for SARS-CoV-2 within one month before enrollment; moderate to severe hepatic impairment (Child-Pugh B or C)
• Major surgery within 8 weeks prior to first dose. Prior laparoscopic nephrectomy within 4 weeks prior to first dose. Minor surgery within 10 days before first dose of study treatment. Complete wound healing from major or minor surgery must have occurred at least prior to first dose
• Corrected QT interval calculated by the Fridericia formula (QTcF) > 460 ms within 10 days per ECG before first dose of study treatment
• History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent
• Pregnant or lactating females
• Inability to swallow study treatment formulation
• Previously identified allergy or hypersensitivity to components of the study treatment formulations
• Any other active malignancy or diagnosis of another malignancy within 2 years before first dose of study treatment. Incidentally diagnosed prostate cancer is allowed if assessed as stage ≤ T2N0M0 and Gleason score ≤ 6
For XL092 + Atezolizumab Combination Therapy Cohorts ONLY
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to active or history of autoimmune disease or immune deficiency, positive test for tuberculosis infection, history of idiopathic pulmonary fibrosis, organizing pneumonia, active pneumonitis, free thyroxine (FT4) outside the laboratory normal reference range
• 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
For XL092 + Avelumab Combination Therapy Cohorts ONLY:
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to active autoimmune disease that might dete

riorate when receiving an immunostimulatory agent
• Administration of a live, attenuated vaccine within 30 days before first dose of study treatment

• UZ Antwerpen
• Cliniques Universitaires Saint-Luc
• UZ Gent