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

Exelixis

Status and phase: Terminated; Phase 1

Conditions: Solid Tumor Cancer; Urothelial Cancer (Urinary Bladder, Ureters, or Renal Pelvis Cancer); Solid Tumor Malignancy; Locally Advanced Solid Tumor; Solid Cancers; Urothelial Cancer of Renal Pelvis; Metastatic Solid Tumor

Treatments: Drug: ADC cytotoxic agents; Drug: XL495

Study type: Interventional

Funder types: Industry

Identifiers

NCT06630247

XL495-101

Details and patient eligibility

About

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.

Enrollment: 9 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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9 participants in 3 patient groups

Dose Escalation XL495

Experimental group

Description:

Group(s) of participants with advanced metastatic tumors who will receive increasing doses of XL495.

Treatment:

Drug: XL495

Dose Finding XL495 + ADC cytotoxic agents

Experimental group

Description:

Group(s) of participants with advanced metastatic tumors who will receive XL495 and Antibody drug conjugate (ADC) cytotoxic agents together at increasing doses.

Treatment:

Drug: XL495

Drug: ADC cytotoxic agents

Expansion XL495 + ADC cytotoxic agents

Experimental group

Description:

Group(s) of participants with urothelial cancer who will receive XL495 and ADC cytotoxic agents at the recommended dosage(s) of expansion (RDE \[s\]) determined during the dose-escalation and dose-finding stages.

Treatment:

Drug: XL495

Drug: ADC cytotoxic agents