Evaluating LOXO-435 for treating cancer with FGFR3 gene changes

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This study investigates the safety, side effects, and effectiveness of LOXO-435, both alone and in combination with standard cancer treatments, for patients with advanced solid tumors that have alterations in the FGFR3 gene. It consists of two phases: Phase 1a focuses on determining the optimal dose through dose escalation and safety assessments, while Phase 1b expands to evaluate the efficacy of LOXO-435 in multiple cohorts, including those with metastatic urothelial cancer. Participants may be involved for up to 30 months or longer if their condition does not worsen.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* Cohort A1, C1, D1, and D2: Locally advanced or metastatic solid tumor malignancy with a qualifying FGFR3 alteration.
* Cohort A2, B2, B5 and B7: Urothelial cancer (UC) that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration.
* Cohorts B1 and B4: Urothelial cancer that is locally advanced or metastatic and have received prior erdafitinib.
* Cohort B6: Muscle Invasive Bladder Cancer with a qualifying FGFR3 alteration.
* Cohort B7: Urothelial cancer that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration and expression of human epidermal growth factor receptor 2 (HER2).
* Cohort B8: Low Grade Intermediate Risk Non-Muscle Invasive Bladder cancer and a qualifying FGFR3 genetic alteration.
* Measurability of disease:

  * Cohort A1, D1, and D2: Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1).
  * Cohorts A2, B1, B2, B4, B5, B7, and C1: Measurable disease required as defined by RECIST v1.1.
  * Cohort B8: Baseline disease which includes at least 1 lesion.
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of:

  * 0 or 1 for Cohorts A1, A2, B5, B6, B7, and B8.
  * Less than or equal to 2 for Cohorts B1, B2, B4, C1, DI and D2.
* Cohort B6: Must be eligible for radical cystectomy plus pelvic lymph node dissection and agree to undergo curative intent standard radical cystectomy plus pelvic lymph node dissection.

Exclusion Criteria:

* Participants with primary central nervous system (CNS) malignancy.
* Untreated or uncontrolled CNS metastases.
* Current evidence of corneal keratopathy or retinal disorder. Individuals with asymptomatic ophthalmic conditions may be eligible.
* 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.
* Cohort D1 only:

  * Have had renal transplantation.
  * Have a known history of nephrotic syndrome.
  * Have uncontrolled fluid overload, including clinically significant ascites, pleural effusion, or peripheral edema.
  * Have uncontrolled hypertension.
  * Are on hemodialysis or similar.
* Cohort D2 only:

  * Have a history of:
  * Ventricular tachycardia or ventricular fibrillation.
  * Hypertrophic obstructive cardiomyopathy unless managed concurrently with atrial fibrillation.
  * Wolff-Parkinson-White syndrome.
  * Second- or third-degree atrioventricular block unless a functioning pacemaker is in place.
  * Heart rate less than (\<) 50 bpm.
  * Have any of these medical conditions:
  * Severe respiratory insufficiency.
  * Sleep apnea syndrome.
  * Myasthenia gravis.
  * Acute narrow-angle glaucoma.
  * Active liver disease or clinically significant hepatic impairment.
  * History of myopathy or rhabdomyolysis with any HMG-CoA reductase inhibitor.

Where it's running

• University of Arizona - Cancer Center
  Tucson, Arizona, United States Recruiting
• City of Hope
  Duarte, California, United States Recruiting
• University of California, Los Angeles (UCLA) - Division of Hematology-Oncology
  Los Angeles, California, United States Recruiting
• University of California - Irvine
  Orange, California, United States Recruiting
• University of California (UC) Davis Comprehensive Cancer Center
  Sacramento, California, United States Recruiting
• Stanford Medicine Cancer Center
  Stanford, California, United States Recruiting

+33 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
• Email: LillyTrials@Lilly.com
• Phone: 1-317-615-4559

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.