|
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 |
|
|
|
|
|
Tumor tissue material |
|
|
|
|
|
Fluoropyrimidine, irinotecan and oxaliplatin, with or without an anti-VEGF monoclonal antibody (bevacizumab) |
|
|
|
|
|
Subjects in the non-biomarker cohort provide archival, if available, or fresh tumor tissue if it can be safely obtained |
|
|
|
|
|
Anti-EGFR monoclonal antibody (cetuximab or panitumumab) |
|
|
|
|
|
Expansion Cohort J (UC, ICI-refractory): Subjects with histologically confirmed, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra) who progressed on or after PD-1/PD-L1 targeting ICI therapy |
|
|
|
|
|
Expansion Cohort K (UC, platinum-refractory): Subjects with histologically confirmed, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra) who progressed on or after first-line platinum-based combination therapy |
|
|
|
|
|
BRAF inhibitor (in combination with cetuximab +/- binimetinib) for subjects with BRAF V600E mutations |
|
|
|
|
|
Expansion Cohort I (UC, Maintenance Therapy): Subjects with histologically confirmed |
|
|
|
|
|
Expansion Cohorts: Subjects must have measurable disease per RECIST 1.1, with exception of Cohort I (UC, Maintenance Therapy) |
|
|
|
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 |
|
|
|
|
|
unresectable, locally advanced or metastatic transitional cell carcinoma of |
|
|
|
|
|
the urothelium (including the renal pelvis, ureter, urinary bladder, or |
|
|
|
|
|
Adequate organ and marrow function |
|
|
|
|
|
urethra) who received first-line chemotherapy of gemcitabine + cisplatin |
|
|
|
|
|
and/or gemcitabine + carboplatin |
|
|
|
|
|
Recovery to baseline or ≤ Grade 1 severity (CTCAE v5) from adverse events (AEs) |
|
|
|
|
Female subjects of childbearing potential must not be pregnant at screening |
|
|
|
|
|
including immune-related adverse events (irAEs), related to any prior |
|
|
|
|
|
treatments, unless AE(s) are clinically nonsignificant and/or stable on |
|
|
|
|
|
supportive therapy |
|
|
|
|
|
Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception |
|
|
|
|
|
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
|
|
|
|
|
|
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
|
|
|
|
|
|
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), prior treatment with avelumab (Cohort J only), or prior treatment with regorafenib and/or TAS-102 (Cohort H only)
|
|
|
|
|
|
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
|
|
|
|
|
|
Corrected QT interval calculated by the Fridericia formula (QTcF) > 450 ms for males and > 470 ms for females. Single ECGs are no longer permitted
|
|
|
|
|
|
Administration of a live, attenuated vaccine within 30 days before first dose of study treatment
|
|
|
|