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Evaluating LOXO-435 for treating cancer with FGFR3 gene changes

FORAGER-1: A Phase 1, Open-Label, Multicenter Study of LOXO-435 (LY3866288) in Locally Advanced or Metastatic Solid Tumors Including Urothelial Cancer With FGFR3 Alterations

PHASE1 · Eli Lilly and Company · NCT05614739

This study is testing a new cancer drug called LOXO-435 to see if it can safely help people with advanced tumors that have changes in the FGFR3 gene, either on its own or with standard treatments.

Quick facts

PhasePHASE1
Study typeInterventional
Enrollment535 (estimated)
Ages18 Years and up
SexAll
SponsorEli Lilly and Company (industry)
Drugs / interventionserdafitinib, pembrolizumab, enfortumab
Locations84 sites (Tucson, Arizona and 83 other locations)
Trial IDNCT05614739 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Ideal candidates include individuals with advanced solid tumors, particularly urothelial cancer, that have a specific FGFR3 genetic alteration.

Not a fit: Patients without FGFR3 alterations or those with non-advanced solid tumors may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new targeted therapy option for patients with FGFR3-altered cancers.

How similar studies have performed: Other studies targeting FGFR3 alterations have shown promise, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
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: Presence of an alteration in FGFR3 or its ligands
  * Cohort A2, B2, B3, and B5: Histological diagnosis of urothelial cancer (UC) that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration
  * Cohorts B1 and B4: Histological diagnosis of urothelial cancer that is locally advanced or metastatic
  * Cohort C1: Must have histological diagnosis of a non-urothelial solid tumor malignancy that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration
* Measurability of disease:

  * Cohort A1 and B3: 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, and C1: Measurable disease required as defined by RECIST v1.1
* Have adequate tumor tissue sample available. Participants with inadequate tissue sample availability may still be considered for enrollment upon review
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 for Cohorts A1, A2, B3, and B5

  * Less than or equal to 2 for Cohorts B1, B2, B4, and C1
* 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, B2, B3 participants must have received at least one prior regimen, and cohorts B1 and B4 participants at least 2 prior regimens, in the locally advanced or metastatic setting
  * There is no restriction on number of prior therapies
* Cohort B5: Participants have not received prior systemic therapy for locally advanced or metastatic UC
* FGFR inhibitor specific requirements:

  * Cohort A1/A2/B3: Prior FGFR inhibitor treatment is permitted but not required
  * Cohort B1/B4: Participants must have been previously treated with erdafitinib
  * Cohort B2, B5, and C1: Participants must be FGFR inhibitor naïve

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

Where this trial is running

Tucson, Arizona and 83 other locations

+34 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Urinary Bladder Neoplasms, Neoplasm Metastasis, Ureteral Neoplasms, Bladder Cancer, Bladder Urothelial Carcinoma, Urinary Bladder Cancer, Urinary Tract Cancer, Renal Pelvis Cancer

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.