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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


  • 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


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.


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
  • Start Date
    January 19, 2023
  • Phase
    Phase 1
  • Study Type


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


  • Urinary Bladder Neoplasms
  • Neoplasm Metastasis
  • Ureteral Neoplasms


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


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


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

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

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

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

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