FORAGER-1: A Study of LOXO-435 (LY3866288) in Participants With Cancer With a Change in a Gene Called FGFR3 (FORAGER-1)

May 18, 2026 updated by: Eli Lilly and Company

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

The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-435 by itself or when it is combined with other standard medicines that treat cancer. 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is an open-label, multi-center, phase 1 study in participants with FGFR3-altered advanced solid tumor malignancy including metastatic urothelial cancer (UC). The study will be conducted in 2 phases: Phase 1a dose escalation (Cohort A1) and dose optimization (Cohort A2) and Phase 1b dose expansion. Phase 1a will assess safety, tolerability, and pharmacokinetics of LOXO-435 to determine the optimal dose for further expansion.

Phase 1b will include 6 dose expansion cohorts to evaluate the efficacy and safety of LOXO-435 as monotherapy or in combinations with pembrolizumab with or without enfortumab vedotin.

Study Type

Interventional

Enrollment (Estimated)

535

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

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

Study Contact Backup

Study Locations

  • Australia
      • Darlinghurst, Australia, NSW 2010
        • Recruiting
        • St Vincent's Hospital
      • Hunter Region, NSW, Australia, 2310
        • Recruiting
        • Calvary Mater Newcastle
      • St Leonards, Australia, 2065
        • Recruiting
        • GenesisCare North Shore
      • Sydney, Australia, 2109
        • Recruiting
        • Macquarie University
  • Canada
      • Toronto, Canada, M5G 2M9
        • Recruiting
        • Princess Margaret Hospital
      • Vancouver, Canada, V5Z 1J3
        • Recruiting
        • British Columbia Cancer Agency
  • China
      • Beijing, China, 100142
        • Recruiting
        • Beijing Cancer hospital
        • Contact:
          • Ben Wan
      • Beijing, China, 100730
        • Recruiting
        • Beijing Hospital
      • Guangdong, China, 510060
        • Recruiting
        • Sun Yat-Sen University- Cancer Center
      • Hangzhou, China, 310002
        • Recruiting
        • Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
      • Shanghai, China, 200000
        • Recruiting
        • Renji Hospital, Shanghai Jiaotong University School of Medicine
      • Tianjin, China, 300060
        • Recruiting
        • Tianjin Medical University Cancer Institute & Hospital
        • Contact:
          • Xin Yao
      • Xi'an, China, 710061
        • Recruiting
        • The First Affiliated Hospital of Xi'an Jiaotong University
      • Zhejiang, China, 310003
        • Recruiting
        • Zhejiang Provincial People's Hospital
  • France
      • Bordeaux, France, 33076
        • Recruiting
        • Institut Bergonie
      • Lyon, France, 69373
        • Recruiting
        • Centre Leon Berard
      • Villejuif, France, 94805
        • Recruiting
        • Institut Gustave Roussy
  • Germany
      • München, Germany, 81675
        • Recruiting
        • Klinikum der Technischen Universitaet Muenchen (TUM Klinikum)
      • Tübingen, Germany, 72016
        • Recruiting
        • Universitaetsklinikum Tuebingen
  • Israel
      • Petah Tikva, Israel, 49100
        • Recruiting
        • Rabin Medical Center, Beilinson Hospital
      • Tel Litwinsky, Israel, 5265601
        • Recruiting
        • Sheba Medical Center
  • Italy
      • Milan, Italy, 20132
        • Recruiting
        • Irccs Ospedale San Raffaele
      • Roma, Italy, 00168
        • Recruiting
        • UOC Fase I - Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
        • Contact:
          • Gennaro Daniele
  • Japan
      • Chiba, Japan, 277-8577
        • Recruiting
        • National Cancer Center Hospital East
        • Contact:
          • Phone Number: 855-569-6305
      • Nagoya, Japan, 464-8681
        • Recruiting
        • Aichi Cancer Center Hospital
      • Tokyo, Japan, 104-0045
        • Recruiting
        • National Cancer Center Hospital
      • Tokyo, Japan, 135-8550
        • Recruiting
        • Cancer Institute Hospital Of JFCR
  • Netherlands
      • GE Rotterdam, Netherlands, 3015
        • Recruiting
        • Erasmus MC
  • Norway
      • Bergen, Norway, 5021
        • Recruiting
        • Haukeland University Hospital
        • Contact:
          • Nina Louise Jebsen
      • Oslo, Norway, 0450
        • Recruiting
        • Oslo University Hospital
  • South Korea
      • Seoul, South Korea, 05505
        • Recruiting
        • Asan Medical Center
      • Seoul, South Korea, 03080
        • Recruiting
        • Seoul National University Hospital
      • Seoul, South Korea, 03722
        • Recruiting
        • Severance Hospital, Yonsei University Health System
      • Seoul, South Korea, 06351
        • Recruiting
        • Samsung Medical Center
  • Spain
      • Barcelona, Spain, 08908
        • Recruiting
        • Institut Català d'Oncologia - L'Hospitalet
      • Madrid, Spain, 28041
        • Recruiting
        • Hospital Universitario 12 de Octubre
        • Contact:
          • Daniel Ernesto Castellano
      • Madrid, Spain, 28050
        • Recruiting
        • South Texas Accelerated Research Therapeutics (START) Madrid - CIOCC
      • Madrid, Spain, 28033
        • Recruiting
        • Fundacion MD Anderson International Espana
      • Santander, Spain, 39008
        • Recruiting
        • Hospital Universitario Marques de Valdecilla
        • Contact:
          • Ignacio Duran Martinez
  • United Kingdom
      • Manchester, United Kingdom, M20 4BX
        • Recruiting
        • The Christie NHS Foundation Trust
        • Contact:
          • Natalie Cook
      • Sheffield, United Kingdom, S10 2SB
        • Recruiting
        • Sheffield Teaching Hospitals NHS Foundation Trust
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85719
        • Recruiting
        • University of Arizona - Cancer Center
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope
      • Los Angeles, California, United States, 90095
        • Recruiting
        • University of California, Los Angeles (UCLA) - Division of Hematology-Oncology
      • Orange, California, United States, 92868
        • Recruiting
        • University of California - Irvine
      • Sacramento, California, United States, 95817
        • Recruiting
        • University of California (UC) Davis Comprehensive Cancer Center
      • Stanford, California, United States, 94305
        • Recruiting
        • Stanford Medicine Cancer Center
    • Florida
      • Orlando, Florida, United States, 32804
        • Recruiting
        • Advent Health
        • Contact:
          • Phone Number: 855-569-6305
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University Hospital
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • The University of Chicago Medical Center (UCMC)
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Indiana University (IU) Melvin and Bren Simon Cancer Center
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70809
        • Recruiting
        • Mary Bird Perkins Cancer Center
      • New Orleans, Louisiana, United States, 70121
        • Recruiting
        • Ochsner Clinic Foundation
    • Maryland
      • Baltimore, Maryland, United States, 21231-2410
        • Recruiting
        • Johns Hopkins Kimmel Cancer Center
        • Contact:
          • Phone Number: 855-569-6305
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
          • Xin Gao
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Barbara Ann Karmanos Cancer Institute
        • Contact:
          • Phone Number: 855-569-6305
    • Missouri
      • St Louis, Missouri, United States, 63108
        • Recruiting
        • Washington University in St. Louis
    • New York
      • New York, New York, United States, 10029
        • Recruiting
        • Icahn School of Medicine at Mount Sinai
        • Contact:
          • Matthew Galsky
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University
      • New York, New York, United States, 10065
        • Recruiting
        • David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
        • Contact:
          • Phone Number: 855-569-6305
      • New York, New York, United States, 10021
        • Not yet recruiting
        • Weill Cornell Medicine
        • Contact:
          • Rohit Jain
      • New York, New York, United States, 10016
        • Recruiting
        • New York University (NYU)
      • Rochester, New York, United States, 14642
        • Recruiting
        • University of Rochester - Wilmot Cancer Institute
      • The Bronx, New York, United States, 10467
        • Recruiting
        • Montefiore Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Recruiting
        • University of North Carolina (UNC) - Chapel Hill
    • Ohio
      • Cincinnati, Ohio, United States, 45267
        • Recruiting
        • University of Cincinnati Medical Center (UCMC)
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • The Ohio State University (OSU)
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma - Health Sciences Center
    • Pennsylvania
      • Lancaster, Pennsylvania, United States, 17601
        • Recruiting
        • Penn Medicine Lancaster General Hospital - Ann B. Barshinger Cancer Institute
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • University of Pennsylvania
        • Contact:
          • Ronac Mamtani
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Thomas Jefferson University
      • Pittsburgh, Pennsylvania, United States, 15213
        • Recruiting
        • University of Pittsburgh Medical Center
      • Pittsburgh, Pennsylvania, United States, 15212
        • Recruiting
        • Allegheny General Hospital
    • South Carolina
      • Myrtle Beach, South Carolina, United States, 29572
        • Recruiting
        • Carolina Urologic Research Center
        • Contact:
          • Neal Shore
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Tennessee Oncology
      • Nashville, Tennessee, United States, 37212
        • Recruiting
        • Vanderbilt University Medical Center
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Sarah Cannon and HCA Research Institute
        • Contact:
          • Phone Number: 855-569-6305
    • Texas
      • Dallas, Texas, United States, 75244
        • Recruiting
        • University of Texas Southwestern
      • Dallas, Texas, United States, 75251
        • Recruiting
        • Texas Oncology, P.A
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • Recruiting
        • University of Utah
        • Contact:
          • Phone Number: 855-569-6305
    • Vermont
      • Burlington, Vermont, United States, 05401
        • Recruiting
        • University of Vermont Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 1a: Cohort A1 LOXO-435 Monotherapy Dose Escalation
LOXO-435 administered orally
Drug: LOXO-435
Oral
Other Names:
  • LY3866288
Experimental: Phase 1a: Cohort A2 LOXO-435 Monotherapy Dose Optimization
LOXO-435 administered orally
Drug: LOXO-435
Oral
Other Names:
  • LY3866288
Experimental: Phase 1b: Cohort B1, B2, B4, and C1 LOXO-435 Monotherapy Dose Expansion
LOXO-435 administered orally
Drug: LOXO-435
Oral
Other Names:
  • LY3866288
Experimental: Phase 1b: Cohort B3 LOXO-435 Plus Pembrolizumab
LOXO-435 administered orally in combination with pembrolizumab administered intravenously (IV)
Drug: Pembrolizumab
IV
Other Names:
  • KEYTRUDA®
Drug: LOXO-435
Oral
Other Names:
  • LY3866288
Experimental: Phase 1b: Cohort B5 LOXO-435 Plus Pembrolizumab Plus Enfortumab Vedotin
LOXO-435 administered orally in combination with pembrolizumab administered IV and enfortumab vedotin administered IV
Drug: Pembrolizumab
IV
Other Names:
  • KEYTRUDA®
Drug: LOXO-435
Oral
Other Names:
  • LY3866288
Drug: enfortumab vedotin
IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1b: To evaluate the preliminary antitumor activity of LOXO-435: Overall response rate (ORR)
Time Frame: Up to approximately 30 months or 2.5 years
ORR per investigator assessed RECIST v1.1
Up to approximately 30 months or 2.5 years
Phase 1a: To determine the recommended dose of LOXO-435: Safety, number of participants with dose-limiting toxicities (DLTs)
Time Frame: Minimum of the first 21-day cycle of LOXO-435 treatment
Number of participants with DLTs
Minimum of the first 21-day cycle of LOXO-435 treatment
Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
Time Frame: Up to approximately 30 months or 2.5 years
A summary of TEAEs and SAEs regardless of causality, will be reported in the Reported Adverse Events module
Up to approximately 30 months or 2.5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To assess the pharmacokinetics (PK) of LOXO-435: Area under the concentration versus time curve (AUC)
Time Frame: Up to 2 months
PK of LOXO-435: AUC
Up to 2 months
To assess the PK of LOXO-435: Minimum plasma concentration (Cmin)
Time Frame: Up to 2 months
PK of LOXO-435: Cmin
Up to 2 months
To evaluate the preliminary antitumor activity of LOXO-435: Duration of response (DoR)
Time Frame: Up to approximately 30 months or 2.5 years
DOR per investigator assessed RECIST 1.1
Up to approximately 30 months or 2.5 years
To evaluate the preliminary antitumor activity of LOXO-435: Time to response (TTR)
Time Frame: Up to approximately 30 months or 2.5 years
TTR
Up to approximately 30 months or 2.5 years
To evaluate the preliminary antitumor activity of LOXO-435: Progression-free survival (PFS)
Time Frame: Up to approximately 30 months or 2.5 years
PFS per investigator assessed RECIST 1.1
Up to approximately 30 months or 2.5 years
To evaluate the preliminary antitumor activity of LOXO-435: Disease control rate (DCR)
Time Frame: Up to approximately 30 months or 2.5 years
DCR per investigator assessed RECIST 1.1
Up to approximately 30 months or 2.5 years
To evaluate the preliminary antitumor activity of LOXO-435: Overall survival (OS)
Time Frame: Up to approximately 30 months or 2.5 years
OS
Up to approximately 30 months or 2.5 years
Change from baseline in bladder-related symptoms, measured by Functional Assessment of Cancer Therapy - Bladder (FACT-Bl) subscale (BlCS)
Time Frame: Cycle 1 Day 1, Cycle 2 Day 1, and Cycle 3 Day 1 (28 day cycles)
The BlCS has 12 items with a total score range of 0 to 48, with higher scores representing better bladder-related symptoms. A ≥ 4-point score change from baseline will be considered as clinically meaningful improvement in bladder-related symptoms
Cycle 1 Day 1, Cycle 2 Day 1, and Cycle 3 Day 1 (28 day cycles)
Change from baseline in physical function, measured by FACT- Physical Well-being Scale (PWB) subscale
Time Frame: Up to approximately 30 months or 2.5 years
The PWB subscale has 7 items with a total score range of 0-28, with higher scores representing better physical function. A ≥ 3-point score change from baseline for a participant will be considered as clinically meaningful improvement in physical function.
Up to approximately 30 months or 2.5 years
To evaluate the preliminary antitumor activity of LOXO-435: Objective response rate (ORR)
Time Frame: Up to approximately 30 months or 2.5 years]
ORR per investigator assessed RECIST 1.1
Up to approximately 30 months or 2.5 years]

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eli Lilly and Company

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 12, 2023

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

June 1, 2027

Study Registration Dates

First Submitted

November 7, 2022

First Submitted That Met QC Criteria

November 7, 2022

First Posted (Actual)

November 14, 2022

Study Record Updates

Last Update Posted (Actual)

May 19, 2026

Last Update Submitted That Met QC Criteria

May 18, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 18594
  • LOXO-FG3-22001 (Other Identifier: Eli Lilly and Company)
  • J4G-OX-JZVA (Other Identifier: Eli Lilly and Company)
  • 2022-502755-59-00 (Other Identifier: EU CTR #)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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