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

Phase 1
Recruiting
Conditions
Solid Cancers
Solid Tumor Cancer
Solid Tumor Malignancy
Urothelial Cancer (Urinary Bladder, Ureters, or Renal Pelvis Cancer)
Metastatic Solid Tumor
Locally Advanced Solid Tumor
Urothelial Cancer of Renal Pelvis
Interventions
Drug: ADC cytotoxic agents
Registration Number
NCT06630247
Lead Sponsor
Exelixis
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
124
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Expansion XL495 + ADC cytotoxic agentsXL495Group(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.
Dose Escalation XL495XL495Group(s) of participants with advanced metastatic tumors who will receive increasing doses of XL495.
Dose Finding XL495 + ADC cytotoxic agentsXL495Group(s) of participants with advanced metastatic tumors who will receive XL495 and Antibody drug conjugate (ADC) cytotoxic agents together at increasing doses.
Dose Finding XL495 + ADC cytotoxic agentsADC cytotoxic agentsGroup(s) of participants with advanced metastatic tumors who will receive XL495 and Antibody drug conjugate (ADC) cytotoxic agents together at increasing doses.
Expansion XL495 + ADC cytotoxic agentsADC cytotoxic agentsGroup(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.
Primary Outcome Measures
NameTimeMethod
Dose-escalation and Dose-finding Stages: Number of Participants with Treatment-Emergent Adverse EventsUp to 18 months
Dose-escalation and Dose-finding Stages: Number of Participants with Dose-limiting ToxicitiesUp to 18 months
Expansion Stage: Number of Participants with Treatment-Emergent Adverse EventsUp to 19 months
Expansion Stage: Objective Response Rate (ORR) As Assessed by Investigator Per RECIST 1.1Until 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.

Secondary Outcome Measures
NameTimeMethod
Dose-escalation and Dose-finding Stages: Concentration of XL495 in PlasmaPre-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 XL495Pre-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 1.1Until 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.

Expansion Stage: Progression-free Survival (PFS), as Assessed by Investigator per RECIST 1.1Until 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.

Expansion Stage: Concentration of XL495 in PlasmaPre-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 XL495Pre-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

Trial Locations

Locations (10)

Exelixis Clinical Site #10

🇺🇸

Jefferson, Louisiana, United States

Exelixis Clinical Site #4

🇺🇸

Denver, Colorado, United States

Exelixis Clinical Site #9

🇺🇸

New Haven, Connecticut, United States

Exelixis Clinical Site #8

🇺🇸

Washington, District of Columbia, United States

Exelixis Clinical Site #7

🇺🇸

New York, New York, United States

Exelixis Clinical SIte #2

🇺🇸

Huntersville, North Carolina, United States

Exelixis Clinical Site #3

🇺🇸

Nashville, Tennessee, United States

Exelixis Clinical Site #5

🇺🇸

Nashville, Tennessee, United States

Exelixis Clinical Site #1

🇺🇸

Austin, Texas, United States

Exelixis Clinical Site #6

🇺🇸

Houston, Texas, United States

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