Clinical trial NCT06630247: A Dose-escalation, Dose-finding, and Expansion Study of XL495 in Participants With Locally Advanced or Metastatic Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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
Keywords: solid tumor
renal tumor
metastatic solid tumor
urothelial carcinoma
Lead sponsor: Exelixis
Sponsor class: INDUSTRY
First posted: 2024-10-08
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This study is divided into three stages:

The first stage is the dose escalation stage that evaluates how much of XL495 alone patients can safely tolerate.

The second is the dose finding stage that evaluates how much of XL495 to give patients in combination with other anti-cancer medications.

The third stage is the expansion stage that evaluates how XL495 performs in patients in combination with other anti-cancer medications.
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Dose-escalation and Dose-finding Stages: Number of Participants with Treatment-Emergent Adverse Events
timeFrame: Up to 18 months
measure: Dose-escalation and Dose-finding Stages: Number of Participants with Dose-limiting Toxicities
timeFrame: Up to 18 months
measure: Expansion Stage: Number of Participants with Treatment-Emergent Adverse Events
timeFrame: Up to 19 months
measure: Expansion Stage: Objective Response Rate (ORR) As Assessed by Investigator Per RECIST 1.1
timeFrame: Until disease progression or death, up to approximately 19 months
Secondary outcomes:
measure: Dose-escalation and Dose-finding Stages: Concentration of XL495 in Plasma
timeFrame: Pre-dose and multiple post-dose time points, up to 18 months
measure: Dose-escalation and Dose-finding Stages: Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Time Curve (AUC) of XL495
timeFrame: Pre-dose and multiple post-dose time points, up to 18 months
measure: Dose-escalation and Dose-finding Stages: PK Parameter Maximum Plasma Concentration of XL495 (Cmax)
timeFrame: Pre-dose and multiple post-dose time points, up to 18 months
measure: Dose-escalation and Dose-finding Stages: PK Parameter Time to Cmax of XL495 (Tmax)
timeFrame: Pre-dose and multiple post-dose time points, up to 18 months
measure: Dose-escalation and Dose-finding Stages: PK Parameter Apparent Clearance with Oral Administration of XL495 (CL/F)
timeFrame: Pre-dose and multiple post-dose time points, up to 18 months
measure: Dose-escalation and Dose-finding Stages: PK Parameter Apparent Terminal Elimination Half-life of XL495 (t1/2)
timeFrame: Pre-dose and multiple post-dose time points, up to 18 months
measure: Expansion Stage: Duration of Response (DOR) As Assessed by Investigator per RECIST 1.1
timeFrame: Until disease progression or death, up to approximately 19 months.
measure: Expansion Stage: Progression-free Survival (PFS), as Assessed by Investigator per RECIST 1.1
timeFrame: Until disease progression or death, up to approximately 19 months.
measure: Expansion Stage: Concentration of XL495 in Plasma
timeFrame: Pre-dose and multiple post-dose time points, up to 18 months
measure: Expansion Stage: Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Time Curve (AUC) of XL495
timeFrame: Pre-dose and multiple post-dose time points, up to 18 months
measure: Expansion Stage: PK Parameter Maximum Plasma Concentration of XL495 (Cmax)
timeFrame: Pre-dose and multiple post-dose time points, up to 18 months
measure: Expansion Stage: PK Parameter Time to Cmax of XL495 (Tmax)
timeFrame: Pre-dose and multiple post-dose time points, up to 18 months
measure: Expansion Stage: PK Parameter Apparent Clearance with Oral Administration of XL495 (CL/F)
timeFrame: Pre-dose and multiple post-dose time points, up to 18 months
measure: Expansion Stage: PK Parameter Apparent Terminal Elimination Half-life of XL495 (t1/2)
timeFrame: Pre-dose and multiple post-dose time points, up to 18 months
Other outcomes:
Locations:
city: Denver
country: United States
facility: Exelixis Clinical Site #4
state: Colorado
city: New Haven
country: United States
facility: Exelixis Clinical Site #9
state: Connecticut
city: Washington
country: United States
facility: Exelixis Clinical Site #8
state: District of Columbia
city: Jefferson
country: United States
facility: Exelixis Clinical Site #10
state: Louisiana
city: New York
country: United States
facility: Exelixis Clinical Site #7
state: New York
city: Huntersville
country: United States
facility: Exelixis Clinical SIte #2
state: North Carolina
city: Nashville
country: United States
facility: Exelixis Clinical Site #3
state: Tennessee
city: Nashville
country: United States
facility: Exelixis Clinical Site #5
state: Tennessee
city: Austin
country: United States
facility: Exelixis Clinical Site #1
state: Texas
city: Houston
country: United States
facility: Exelixis Clinical Site #6
state: Texas
Study officials:
References: