Company Decision

The goal of this study is to obtain safety, tolerability, PK, and preliminary clinical antitumor activity for XL495 as a single agent and in combination with select cytotoxic agents in participants with locally advanced or metastatic tumors for whom life-prolonging therapies do not exist or available therapies are intolerable/no longer effective.

Inclusion Criteria

• For All Participants

  • Have received at least one standard therapy unless it does not exist, or available therapies are intolerable or no longer effective.
  • For participants, who qualify for approved molecularly selected therapies such as RAS inhibitors, they must have progressed on, relapsed from, been intolerant to, ineligible, or refused those therapies.

• Expansion Stage

  • Diagnosis of metastatic advanced UC (primary tumor: renal pelvis, ureter, urinary bladder, or urethra).
  • At least one measurable lesion as defined by RECIST, version 1.1.
  • Participants must be eligible for sacituzumab govitecan treatment as their next line of therapy.

• At least one but no more than 3 prior lines of therapy.

• Eastern Cooperative Oncology Group (ECOG) Performance Status (0-2 for monotherapy; 0-1 for combo)

Exclusion Criteria

• Prior anticancer treatment, including:

  • Radiation therapy within 2 weeks before first dose of study treatment.

• Known brain metastases or cranial epidural disease

• Current or recent severe illness

• Known history or positive test for human immunodeficiency virus (HIV) unless meets specific criteria.

• Active infection with hepatitis B virus or hepatitis C virus.

• Malabsorption syndrome.

• History of solid organ, autologous or allogenic stem cell transplant.

• Diagnosis of another cancer 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 standard therapy.

• Active autoimmune disease with skin involvement.