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

Phase 1TerminatedNCT06630247

Exelixis9 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Solid Cancers Solid Tumor Cancer Solid Tumor Malignancy Urothelial Cancer (Urinary Bladder, Ureters, or Renal Pelvis Cancer)Metastatic Solid Tumor

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (10)

Exelixis Clinical Site #4

Denver, Colorado, United States

Exelixis Clinical Site #9

New Haven, Connecticut, United States

Exelixis Clinical Site #8

Washington D.C., District of Columbia, United States

Exelixis Clinical Site #10

Jefferson, Louisiana, 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

Outcomes

Primary Outcomes

Dose-escalation and Dose-finding Stages: Number of Participants with Treatment-Emergent Adverse Events

Time frame: Up to 18 months

Dose-escalation and Dose-finding Stages: Number of Participants with Dose-limiting Toxicities

Time frame: Up to 18 months

Expansion Stage: Number of Participants with Treatment-Emergent Adverse Events

Time frame: 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.

Time frame: Until disease progression or death, up to approximately 19 months

Secondary Outcomes

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

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

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

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

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

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

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.

Time frame: 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.

Time frame: 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

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

Expansion Stage: PK Parameter Maximum Plasma Concentration of XL495 (Cmax)

Time frame: 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

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

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

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

Overview

Conditions

Interventions

Eligibility

Locations (10)

Outcomes

Primary Outcomes

Secondary Outcomes