A Dose-escalation, Dose-finding, and Expansion Study of XL495 in Participants With Locally Advanced or Metastatic Solid Tumors

A Dose-escalation, Dose-finding, and Expansion Study of XL495 as a Single Agent and in Combination Therapy in Participants With Locally Advanced or Metastatic Solid Tumors

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.