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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: J4G-OX-JZVA, 2022-502755-59-00
  • NTC ID: NCT05614739
  • Sponsor: Eli Lilly and Company
A Study of LOXO-435 in Patients With Cancer With a Change in a Gene Called FGFR3

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 (mUC). The study will be conducted in 2 phases: Dose escalation (1a) and dose expansion (1b). Phase 1a will assess safety, tolerability, and pharmacokinetics of LOXO-435 to determine the recommended phase 2 dose (RP2D). Phase 1b will include 4 dose expansion cohorts of patients with prespecified activating FGFR3 alterations to evaluate the efficacy and safety of LOXO-435 at the RP2D. Cohort B will enroll pts with mUC 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 19, 2023
  • Phase
    Phase 1
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Phase 1a: To determine the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) of LOXO-435: Number of patients with dose-limiting toxicities (DLTs)

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

Primary Outcome 2 - Measure: Phase 1b: To evaluate the preliminary antitumor activity of LOXO-435: Overall response rate (ORR)

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

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 A (Dose Escalation): Presence of an alteration in FGFR3 or its ligands deemed as a clinically or potentially clinically relevant alteration by the treating Investigator.

- 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:
Phase 1a: measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1)

- Phase 1b: 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.
Patient has received all standard therapies for which the patient was deemed to be an appropriate candidate by the treating Investigator; OR the patient 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 B1: Patients must have been previously treated with a FGFR inhibitor.

- Cohort B2, B3, C1: Patients must be FGFR inhibitor naïve.
Exclusion Criteria:
Patients 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

- Patients who are pregnant, lactating, or plan to breastfeed during the study or within 6 months of the last dose of study treatment

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Ryan Widau, PhD

Role: Study Director

Affiliation: Loxo Oncology, Inc.

Overall Contact

Name: Ryan Widau, PhD

Phone: 855-569-6305

Email: clinicaltrials@loxooncology.com

LOCATION

Facility Status Contact
Facility: Massachusetts General Hospital
Boston, Massachusetts 02114
United States
Status: Recruiting Contact: Contact

855-569-6305
Facility: Washington University School of Medicine
Saint Louis, Missouri 63110
United States
Status: Recruiting Contact: Contact

855-569-6305
Facility: David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
New York, New York 10065
United States
Status: Recruiting Contact: Contact

855-569-6305
Facility: Carolina Urologic Research Center
Myrtle Beach, South Carolina 29572
United States
Status: Recruiting Contact: Contact

855-569-6305
Facility: Sarah Cannon and HCA Research Institute
Nashville, Tennessee 37203
United States
Status: Recruiting Contact: Contact

855-569-6305