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

NCT06630247 | Terminated Phase 1 FDA Drug

• 1 other identifier: XL495-101
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 10

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.

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

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (14)

• 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

Study Arms (3)

Dose Escalation XL495

EXPERIMENTAL

Group(s) of participants with advanced metastatic tumors who will receive increasing doses of XL495.

Drug: XL495

Dose Finding XL495 + ADC cytotoxic agents

EXPERIMENTAL

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; Drug: ADC cytotoxic agents

Expansion XL495 + ADC cytotoxic agents

EXPERIMENTAL

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; Drug: ADC cytotoxic agents

Interventions

XL495 DRUG

oral doses of XL495

Dose Escalation XL495; Dose Finding XL495 + ADC cytotoxic agents; Expansion XL495 + ADC cytotoxic agents

ADC cytotoxic agents DRUG

intravenous infusion of anti-cancer combination agent

Dose Finding XL495 + ADC cytotoxic agents; Expansion XL495 + ADC cytotoxic agents

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Exelixis: lead

Study Sites (10)

Exelixis Clinical Site #4

Denver, Colorado, 80218, United States

Location

Exelixis Clinical Site #9

New Haven, Connecticut, 06511, United States

Location

Exelixis Clinical Site #8

Washington D.C., District of Columbia, 20007, United States

Location

Exelixis Clinical Site #10

Jefferson, Louisiana, 70121, United States

Location

Exelixis Clinical Site #7

New York, New York, 10029, United States

Location

Exelixis Clinical SIte #2

Huntersville, North Carolina, 28078, United States

Location

Exelixis Clinical Site #3

Nashville, Tennessee, 37203, United States

Location

Exelixis Clinical Site #5

Nashville, Tennessee, 37203, United States

Location

Exelixis Clinical Site #1

Austin, Texas, 78758, United States

Location

Exelixis Clinical Site #6

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Carcinoma, Renal Cell; Carcinoma, Transitional Cell

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 4, 2024
• First Posted: October 8, 2024
• Study Start: October 17, 2024
• Primary Completion: May 7, 2025
• Study Completion: May 7, 2025
• Last Updated: June 25, 2025

Record last verified: 2025-06

Locations

US (10)