STELLAR-001: This phase I study is evaluating how safe, tolerable and effective a new drug (XL092) is alone, or combined with immunotherapy (Atezolizumab or Avelumab) in people with inoperable, locally advanced or metastatic solid cancersA 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

Inclusion

• 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.