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.

Study Overview

• Status: Terminated
• Conditions: Metastatic Solid Tumor; Solid Tumor Cancer; Urothelial Cancer of Renal Pelvis; Solid Cancers; Locally Advanced Solid Tumor; Solid Tumor Malignancy; Urothelial Cancer (Urinary Bladder, Ureters, or Renal Pelvis Cancer)
• Intervention / Treatment: Drug: XL495; Drug: ADC cytotoxic agents

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Exelixis Clinical Site #4
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Exelixis Clinical Site #9
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Exelixis Clinical Site #8
  • Louisiana
    • Jefferson, Louisiana, United States, 70121
      • Exelixis Clinical Site #10
  • New York
    • New York, New York, United States, 10029
      • Exelixis Clinical Site #7
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Exelixis Clinical Site #2
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Exelixis Clinical Site #3
    • Nashville, Tennessee, United States, 37203
      • Exelixis Clinical Site #5
  • Texas
    • Austin, Texas, United States, 78758
      • Exelixis Clinical Site #1
    • Houston, Texas, United States, 77030
      • Exelixis Clinical Site #6

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation XL495; Group(s) of participants with advanced metastatic tumors who will receive increasing doses of XL495.	Drug: XL495; oral doses of XL495
Experimental: Dose Finding XL495 + ADC cytotoxic agents; Group(s) of participants with advanced metastatic tumors who will receive XL495 and Antibody drug conjugate (ADC) cytotoxic agents together at increasing doses.	Drug: XL495; oral doses of XL495; Drug: ADC cytotoxic agents; intravenous infusion of anti-cancer combination agent
Experimental: Expansion XL495 + ADC cytotoxic agents; 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.	Drug: XL495; oral doses of XL495; Drug: ADC cytotoxic agents; intravenous infusion of anti-cancer combination agent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-escalation and Dose-finding Stages: Number of Participants with Treatment-Emergent Adverse Events		Up to 18 months
Dose-escalation and Dose-finding Stages: Number of Participants with Dose-limiting Toxicities		Up to 18 months
Expansion Stage: Number of Participants with Treatment-Emergent Adverse Events		Up to 19 months
Expansion Stage: Objective Response Rate (ORR) As Assessed by Investigator Per RECIST 1.1	ORR is defined as the percentage of participants with the best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), as assessed by the Investigator per RECIST 1.1.	Until disease progression or death, up to approximately 19 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-escalation and Dose-finding Stages: Concentration of XL495 in Plasma		Pre-dose and multiple post-dose time points, up to 18 months
Dose-escalation and Dose-finding Stages: Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Time Curve (AUC) of XL495		Pre-dose and multiple post-dose time points, up to 18 months
Dose-escalation and Dose-finding Stages: PK Parameter Maximum Plasma Concentration of XL495 (Cmax)		Pre-dose and multiple post-dose time points, up to 18 months
Dose-escalation and Dose-finding Stages: PK Parameter Time to Cmax of XL495 (Tmax)		Pre-dose and multiple post-dose time points, up to 18 months
Dose-escalation and Dose-finding Stages: PK Parameter Apparent Clearance with Oral Administration of XL495 (CL/F)		Pre-dose and multiple post-dose time points, up to 18 months
Dose-escalation and Dose-finding Stages: PK Parameter Apparent Terminal Elimination Half-life of XL495 (t1/2)		Pre-dose and multiple post-dose time points, up to 18 months
Expansion Stage: Duration of Response (DOR) As Assessed by Investigator per RECIST 1.1	DOR is defined as the time from the first documented objective response (CR or PR) until the earlier of radiographic progressive disease (PD) as assessed by the investigator per RECIST 1.1 or censoring due to lack of these events or start of non-protocol anti-cancer therapy.	Until disease progression or death, up to approximately 19 months.
Expansion Stage: Progression-free Survival (PFS), as Assessed by Investigator per RECIST 1.1	PFS is defined as the time from start of study treatment to the earlier of either radiographic PD per RECIST 1.1 or death from any cause.	Until disease progression or death, up to approximately 19 months.
Expansion Stage: Concentration of XL495 in Plasma		Pre-dose and multiple post-dose time points, up to 18 months
Expansion Stage: Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Time Curve (AUC) of XL495		Pre-dose and multiple post-dose time points, up to 18 months
Expansion Stage: PK Parameter Maximum Plasma Concentration of XL495 (Cmax)		Pre-dose and multiple post-dose time points, up to 18 months
Expansion Stage: PK Parameter Time to Cmax of XL495 (Tmax)		Pre-dose and multiple post-dose time points, up to 18 months
Expansion Stage: PK Parameter Apparent Clearance with Oral Administration of XL495 (CL/F)		Pre-dose and multiple post-dose time points, up to 18 months
Expansion Stage: PK Parameter Apparent Terminal Elimination Half-life of XL495 (t1/2)		Pre-dose and multiple post-dose time points, up to 18 months

Collaborators and Investigators

• Sponsor: Exelixis

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2024
• Primary Completion (Actual): May 7, 2025
• Study Completion (Actual): May 7, 2025

Study Registration Dates

• First Submitted: October 4, 2024
• First Submitted That Met QC Criteria: October 4, 2024
• First Posted (Actual): October 8, 2024

Study Record Updates

• Last Update Posted (Estimated): June 25, 2025
• Last Update Submitted That Met QC Criteria: June 19, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: solid tumor; metastatic solid tumor; urothelial carcinoma; renal tumor
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Pelvic Neoplasms
• Other Study ID Numbers: XL495-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No