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Brief Title: LOXO-435 in Patients With Cancer With a Change in a Gene Called FGFR3

An Open-Label, Multicenter Study of LOXO-435 (LY3866288) In Advanced Solid Tumor Malignancies With FGFR3 Alterations

INTRODUCTION

  • Org Study ID: LOXO-FG3-22001
  • Secondary ID: N/A
  • NCT ID: NCT05614739
  • Sponsor: Eli Lilly and Company

DESCRIPTION

Learn more about LOXO-435 for patients who have the FGFR3 gene in their advanced bladder cancer. Click this link: Loxo-435_Plain_Language_Summary NCT05614739

BRIEF SUMMARY

The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-435. LOXO-435 may be used to treat cancer of the cells that line the urinary system and other solid tumor cancers that have a change in a particular gene (known as the FGFR3 gene). Participation could last up to 30 months (2.5 years) and possibly longer if the disease does not get worse.

DETAILED DESCRIPTION

This is an open-label, multi-center, phase 1a/b study in participants with FGFR3-altered advanced solid tumors, including metastatic urothelial cancer (UC). The study will be conducted in 2 phases: Dose escalation and dose optimization (1a) and dose expansion (1b). Phase 1a will include up to 2 cohorts to assess safety, tolerability, and pharmacokinetics of LOXO-435 to determine the recommended phase 2 dose (RP2D) (or optimal dose). Phase 1b will include 4 dose expansion cohorts of participants with prespecified activating FGFR3 alterations to evaluate the efficacy and safety of LOXO-435 at the RP2D. Cohort B will enroll pts with metastatic UC and includes three cohorts to evaluate LOXO-435 as monotherapy (B1, B2) and in combination with pembrolizumab (B3). Cohort C will enroll pts with non-UC advanced solid tumors and includes a cohort to evaluate LOXO-435 as monotherapy (C1).

  • Overall Status
    Recruiting
  • Start Date
    January 12, 2023
  • Phase
    Phase 1
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Phase 1a: To determine the recommended phase 2 dose (RP2D)/optimal dose of LOXO-435: Safety

Primary Outcome 1 - Timeframe: Minimum of the first 21-day cycle of LOXO-435 treatment

Primary Outcome 2 - Measure: number of participants with dose-limiting toxicities (DLTs)

Primary Outcome 2 - Timeframe: Up to approximately 30 months or 2.5 years

Primary Outcome 3 - Measure: Phase 1b: To evaluate the preliminary antitumor activity of LOXO-435: Overall response rate (ORR)

Primary Outcome 3 - Timeframe: N/A

CONDITION

  • Urinary Bladder Neoplasms
  • Neoplasm Metastasis
  • Ureteral Neoplasms

ELIGIBILITY

Inclusion Criteria:
* Have solid tumor cancer with an FGFR3 pathway alteration on molecular testing in tumor or blood sample that is deemed as actionable.
* Cohort A1 (Dose Escalation): Presence of an alteration in FGFR3 or its ligands.

- * Cohort A2 (Dose Optimization): Histological diagnosis of urothelial cancer (UC) that is locally advanced or metastatic with a qualifying FGFR3 alteration.

- * Cohorts B1, B2 and B3 (Dose Expansion): Histological diagnosis of urothelial cancer that is locally advanced or metastatic with a prespecified activating FGFR3 alteration.

- * Cohort C (Dose Expansion): Must have histological diagnosis of a non-urothelial solid tumor malignancy that is locally advanced or metastatic with a prespecified activating FGFR3 alteration.

- * Measurability of disease:
* Cohort A1: Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1)

- * Cohorts A2, B1, B2, B3, and C1: Measurable disease required as defined by RECIST v1.1

- * Have adequate archival tumor tissue sample available or undergo a screening biopsy if allowed per country-specific regulations.

- * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

- * Prior Systemic Therapy Criteria:
* Cohort A1/C1: Participant has received all standard therapies for which the participant was deemed to be an appropriate candidate by the treating Investigator; OR the participant is refusing the remaining most appropriate standard of care treatment; OR there is no standard therapy available for the disease. There is no restriction on number of prior therapies.

- * Cohort A2/B1/B2/B3: Participants must have received at least one prior regimen in the advanced or metastatic setting. There is no restriction on number of prior therapies.

- * FGFR inhibitor specific requirements:
* Cohort A1/A2: Prior FGFR inhibitor treatment is permitted, but not required.

- * Cohort B1: Participants must have been previously treated with a FGFR inhibitor.

- * Cohort B2, B3, C1: Participants must be FGFR inhibitor naïve.
Exclusion Criteria:
* Participants with primary central nervous system (CNS) malignancy.

- * Known or suspected history of uncontrolled CNS metastases.

- * Current evidence of corneal keratopathy or retinal disorder.

- * Have a history and/or current evidence of extensive tissue calcification.

- * Any serious unresolved toxicities from prior therapy.

- * Significant cardiovascular disease.

- * Prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF).

- * Active uncontrolled systemic infection or other clinically significant medical conditions.

- * Participants who are pregnant, lactating, or plan to breastfeed during the study or within 6 months of the last dose of study treatment. Participants who have stopped breastfeeding may be enrolled.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Ryan Widau, PhD

Role: Study Director

Affiliation: Eli Lilly and Company

Overall Contact

Name: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

Phone: 13176154559

Email: [email protected]

LOCATION

Facility Status Contact
Facility: City of Hope Medical Center
Duarte, California 91010
United States
Status: Recruiting Contact: N/A
Facility: UCLA Department of Medicine-Hematology/Oncology
Santa Monica, California 90095
United States
Status: Recruiting Contact: N/A
Facility: Advent Health Hematology and Oncology
Celebration, Florida 34747
United States
Status: Recruiting Contact: N/A
Facility: Winship Cancer Institute, Emory University
Atlanta, Georgia 30322
United States
Status: Recruiting Contact: N/A
Facility: The University of Chicago Medical Center
Chicago, Illinois 60637
United States
Status: Recruiting Contact: N/A
Facility: SKCCC at Johns Hopkins
Baltimore, Maryland 21287
United States
Status: Recruiting Contact: N/A
Facility: Massachusetts General Hospital
Boston, Massachusetts 02144
United States
Status: Recruiting Contact: N/A
Facility: Karmanos Cancer Institute
Detroit, Michigan 48201
United States
Status: Recruiting Contact: N/A
Facility: Washington University School of Medicine
Saint Louis, Missouri 63110
United States
Status: Recruiting Contact: N/A
Facility: Laura and Isaac Perlmutter Cancer Center
New York, New York 10016
United States
Status: Recruiting Contact: N/A
Facility: Icahn School of Medicine at Mount Sinai
New York, New York 10029
United States
Status: Recruiting Contact: N/A
Facility: Memorial Sloan Kettering Cancer Center
New York, New York 10065
United States
Status: Recruiting Contact: N/A
Facility: University of North Carolina at Chapel Hill
Chapel Hill, North Carolina 27599-7305
United States
Status: Recruiting Contact: N/A
Facility: University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
United States
Status: Recruiting Contact: N/A
Facility: Penn Medicine: University of Pennsylvania Health System/Perelman Center for Advanced Medicine
Philadelphia, Pennsylvania 19104
United States
Status: Recruiting Contact: N/A
Facility: University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania 15232
United States
Status: Recruiting Contact: N/A
Facility: Carolina Urologic Research Center
Myrtle Beach, South Carolina 29572
United States
Status: Recruiting Contact: N/A
Facility: Tennessee Oncology PLLC
Nashville, Tennessee 37204
United States
Status: Recruiting Contact: N/A
Facility: University of Texas Southwestern Medical Center
Dallas, Texas 75390
United States
Status: Recruiting Contact: N/A
Facility: MD Anderson Cancer Center
Houston, Texas 77030-4009
United States
Status: Recruiting Contact: N/A
Facility: Huntsman Cancer Institute
Salt Lake City, Utah 84112
United States
Status: Recruiting Contact: N/A