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

NCT ID: NCT05614739

Last Updated: 2025-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

535 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-01-12

Study Completion Date

2027-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Urinary Bladder Neoplasms Neoplasm Metastasis Ureteral Neoplasms

Keywords

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Bladder Cancer Bladder Urothelial Carcinoma Urinary Bladder Cancer Urinary Tract Cancer Renal Pelvis Cancer Ureter Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Cohort A2 is randomized

Study Groups

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Phase 1a: Cohort A1 LOXO-435 Monotherapy Dose Escalation

LOXO-435 administered orally

Group Type EXPERIMENTAL

LOXO-435

Intervention Type DRUG

Oral

Phase 1a: Cohort A2 LOXO-435 Monotherapy Dose Optimization

LOXO-435 administered orally

Group Type EXPERIMENTAL

LOXO-435

Intervention Type DRUG

Oral

Phase 1b: Cohort B1, B2, B4, and C1 LOXO-435 Monotherapy Dose Expansion

LOXO-435 administered orally

Group Type EXPERIMENTAL

LOXO-435

Intervention Type DRUG

Oral

Phase 1b: Cohort B3 LOXO-435 Plus Pembrolizumab

LOXO-435 administered orally in combination with pembrolizumab administered intravenously (IV)

Group Type EXPERIMENTAL

LOXO-435

Intervention Type DRUG

Oral

Pembrolizumab

Intervention Type DRUG

IV

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

Group Type EXPERIMENTAL

LOXO-435

Intervention Type DRUG

Oral

Pembrolizumab

Intervention Type DRUG

IV

enfortumab vedotin

Intervention Type DRUG

IV

Interventions

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LOXO-435

Oral

Intervention Type DRUG

Pembrolizumab

IV

Intervention Type DRUG

enfortumab vedotin

IV

Intervention Type DRUG

Other Intervention Names

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LY3866288

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eli Lilly and Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

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University of Arizona - Cancer Center

Tucson, Arizona, United States

Site Status RECRUITING

City of Hope

Duarte, California, United States

Site Status RECRUITING

University of California, Los Angeles (UCLA) - Division of Hematology-Oncology

Los Angeles, California, United States

Site Status RECRUITING

University of California - Irvine

Orange, California, United States

Site Status RECRUITING

University of California (UC) Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status RECRUITING

Stanford Cancer Center

Stanford, California, United States

Site Status RECRUITING

Advent Health

Orlando, Florida, United States

Site Status RECRUITING

Emory University Hospital

Atlanta, Georgia, United States

Site Status RECRUITING

The University of Chicago Medical Center (UCMC)

Chicago, Illinois, United States

Site Status RECRUITING

Indiana University (IU) Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status RECRUITING

Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, United States

Site Status RECRUITING

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status RECRUITING

Johns Hopkins Kimmel Cancer Center

Baltimore, Maryland, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status RECRUITING

Washington University in St. Louis

St Louis, Missouri, United States

Site Status RECRUITING

New York University (NYU)

New York, New York, United States

Site Status RECRUITING

Weill Cornell Medicine

New York, New York, United States

Site Status NOT_YET_RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status RECRUITING

Columbia University

New York, New York, United States

Site Status RECRUITING

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

University of Rochester - Wilmot Cancer Institute

Rochester, New York, United States

Site Status RECRUITING

Montefiore Medical Center

The Bronx, New York, United States

Site Status RECRUITING

University of North Carolina (UNC) - Chapel Hill

Chapel Hill, North Carolina, United States

Site Status RECRUITING

University of Cincinnati Medical Center (UCMC)

Cincinnati, Ohio, United States

Site Status RECRUITING

The Ohio State University (OSU)

Columbus, Ohio, United States

Site Status RECRUITING

University of Oklahoma - Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status RECRUITING

Penn Medicine Lancaster General Hospital - Ann B. Barshinger Cancer Institute

Lancaster, Pennsylvania, United States

Site Status RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status NOT_YET_RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States

Site Status RECRUITING

Sarah Cannon and HCA Research Institute

Nashville, Tennessee, United States

Site Status RECRUITING

Tennessee Oncology

Nashville, Tennessee, United States

Site Status RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status NOT_YET_RECRUITING

University of Texas Southwestern

Dallas, Texas, United States

Site Status RECRUITING

Texas Oncology, P.A

Dallas, Texas, United States

Site Status RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

University of Utah

Salt Lake City, Utah, United States

Site Status RECRUITING

University of Vermont Medical Center

Burlington, Vermont, United States

Site Status NOT_YET_RECRUITING

Inova Schar Cancer Institute

Falls Church, Virginia, United States

Site Status NOT_YET_RECRUITING

St Vincent's Hospital

Darlinghurst, , Australia

Site Status RECRUITING

Calvary Mater Newcastle

Hunter Region, NSW, , Australia

Site Status RECRUITING

GenesisCare North Shore

St Leonards, , Australia

Site Status RECRUITING

Macquarie University

Sydney, , Australia

Site Status RECRUITING

Princess Margaret Hospital

Toronto, , Canada

Site Status RECRUITING

British Columbia Cancer Agency

Vancouver, , Canada

Site Status RECRUITING

Beijing Cancer hospital

Beijing, , China

Site Status RECRUITING

Beijing Hospital

Beijing, , China

Site Status RECRUITING

Sun Yat-Sen University- Cancer Center

Guangdong, , China

Site Status RECRUITING

Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University

Hangzhou, , China

Site Status RECRUITING

Renji Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, , China

Site Status RECRUITING

Tianjin Medical University Cancer Institute & Hospital

Tianjin, , China

Site Status RECRUITING

First Affiliated Hospital of Medical College of Xian jiaotong University

Xi'an, , China

Site Status RECRUITING

Zhejiang Provincial People's Hospital

Zhejiang, , China

Site Status RECRUITING

Institut Bergonie

Bordeaux, , France

Site Status RECRUITING

Centre Leon Berard

Lyon, , France

Site Status RECRUITING

Institut Gustave Roussy

Villejuif, , France

Site Status RECRUITING

Universitaetsklinikum Schleswig-Holstein - Campus Luebeck

Lübeck, , Germany

Site Status NOT_YET_RECRUITING

Klinikum der Technischen Universitaet Muenchen (TUM Klinikum)

München, , Germany

Site Status RECRUITING

Universitaetsklinikum Tuebingen

Tübingen, , Germany

Site Status RECRUITING

Rabin Medical Center, Beilinson Hospital

Petah Tikva, , Israel

Site Status RECRUITING

Sheba Medical Center

Tel Litwinsky, , Israel

Site Status RECRUITING

IRCCS Ospedale San Raffaele

Milan, , Italy

Site Status RECRUITING

UOC Fase I - Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore

Roma, , Italy

Site Status RECRUITING

National Cancer Center Hospital East

Chiba, , Japan

Site Status RECRUITING

Aichi Cancer Center Hospital

Nagoya, , Japan

Site Status RECRUITING

National Cancer Center Hospital

Tokyo, , Japan

Site Status RECRUITING

Cancer Institute Hospital of JFCR

Tokyo, , Japan

Site Status RECRUITING

Erasmus MC

GE Rotterdam, , Netherlands

Site Status RECRUITING

Haukeland University Hospital

Bergen, , Norway

Site Status RECRUITING

Oslo University Hospital

Oslo, , Norway

Site Status RECRUITING

Seoul National University Hospital

Seoul, , South Korea

Site Status RECRUITING

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status RECRUITING

Asan Medical Center

Seoul, , South Korea

Site Status RECRUITING

Samsung Medical Center

Seoul, , South Korea

Site Status RECRUITING

Institut Catala d'Oncologia - L'Hospitalet

Barcelona, , Spain

Site Status RECRUITING

Fundacion MD Anderson International Espana

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status RECRUITING

South Texas Accelerated Research Therapeutics (START) Madrid - CIOCC

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario Marques De Valdecilla

Santander, , Spain

Site Status RECRUITING

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status RECRUITING

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia Canada China France Germany Israel Italy Japan Netherlands Norway South Korea Spain United Kingdom

Central Contacts

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Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

Role: CONTACT

Phone: 1-317-615-4559

Email: [email protected]

Physicians interested in becoming principal investigators please contact

Role: CONTACT

Email: [email protected]

Related Links

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https://trials.lilly.com/en-US/trial/367675

A Study of LOXO-435 in Patients With Cancer With a Change in a Gene Called FGFR3

Other Identifiers

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J4G-OX-JZVA

Identifier Type: OTHER

Identifier Source: secondary_id

2022-502755-59-00

Identifier Type: OTHER

Identifier Source: secondary_id

LOXO-FG3-22001

Identifier Type: OTHER

Identifier Source: secondary_id

18594

Identifier Type: -

Identifier Source: org_study_id