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

June 19, 2025 updated by: Exelixis

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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
9

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Dose-escalation and Dose-finding Stages: Number of Participants with Treatment-Emergent Adverse Events
Time Frame: Up to 18 months
Up to 18 months
Dose-escalation and Dose-finding Stages: Number of Participants with Dose-limiting Toxicities
Time Frame: Up to 18 months
Up to 18 months
Expansion Stage: Number of Participants with Treatment-Emergent Adverse Events
Time Frame: Up to 19 months
Up to 19 months
Expansion Stage: Objective Response Rate (ORR) As Assessed by Investigator Per RECIST 1.1
Time Frame: Until disease progression or death, up to approximately 19 months
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Dose-escalation and Dose-finding Stages: Concentration of XL495 in Plasma
Time Frame: Pre-dose and multiple post-dose time points, up to 18 months
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
Time Frame: Pre-dose and multiple post-dose time points, up to 18 months
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)
Time Frame: Pre-dose and multiple post-dose time points, up to 18 months
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)
Time Frame: Pre-dose and multiple post-dose time points, up to 18 months
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)
Time Frame: Pre-dose and multiple post-dose time points, up to 18 months
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)
Time Frame: Pre-dose and multiple post-dose time points, up to 18 months
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
Time Frame: Until disease progression or death, up to approximately 19 months.
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
Time Frame: Until disease progression or death, up to approximately 19 months.
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
Time Frame: Pre-dose and multiple post-dose time points, up to 18 months
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
Time Frame: Pre-dose and multiple post-dose time points, up to 18 months
Pre-dose and multiple post-dose time points, up to 18 months
Expansion Stage: PK Parameter Maximum Plasma Concentration of XL495 (Cmax)
Time Frame: Pre-dose and multiple post-dose time points, up to 18 months
Pre-dose and multiple post-dose time points, up to 18 months
Expansion Stage: PK Parameter Time to Cmax of XL495 (Tmax)
Time Frame: Pre-dose and multiple post-dose time points, up to 18 months
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)
Time Frame: Pre-dose and multiple post-dose time points, up to 18 months
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)
Time Frame: Pre-dose and multiple post-dose time points, up to 18 months
Pre-dose and multiple post-dose time points, up to 18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Exelixis

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 17, 2024

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 7, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 7, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 4, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 4, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 8, 2024

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 19, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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