FORAGER-1: A Study of LOXO-435 (LY3866288) in Participants With Cancer With a Change in a Gene Called FGFR3
FORAGER-1
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
4 other identifiers
interventional
535
14 countries
82
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jan 2023
Longer than P75 for phase_1
82 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 7, 2022
CompletedFirst Posted
Study publicly available on registry
November 14, 2022
CompletedStudy Start
First participant enrolled
January 12, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2027
May 19, 2026
May 1, 2026
4.4 years
November 7, 2022
May 18, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Phase 1a: To determine the recommended dose of LOXO-435: Safety, number of participants with dose-limiting toxicities (DLTs)
Number of participants with DLTs
Minimum of the first 21-day cycle of LOXO-435 treatment
Phase 1b: To evaluate the preliminary antitumor activity of LOXO-435: Overall response rate (ORR)
ORR per investigator assessed RECIST v1.1
Up to approximately 30 months or 2.5 years
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
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 Outcomes (10)
To assess the pharmacokinetics (PK) of LOXO-435: Area under the concentration versus time curve (AUC)
Up to 2 months
To assess the PK of LOXO-435: Minimum plasma concentration (Cmin)
Up to 2 months
To evaluate the preliminary antitumor activity of LOXO-435: Objective response rate (ORR)
Up to approximately 30 months or 2.5 years]
To evaluate the preliminary antitumor activity of LOXO-435: Duration of response (DoR)
Up to approximately 30 months or 2.5 years
To evaluate the preliminary antitumor activity of LOXO-435: Time to response (TTR)
Up to approximately 30 months or 2.5 years
- +5 more secondary outcomes
Study Arms (5)
Phase 1a: Cohort A1 LOXO-435 Monotherapy Dose Escalation
EXPERIMENTALLOXO-435 administered orally
Phase 1a: Cohort A2 LOXO-435 Monotherapy Dose Optimization
EXPERIMENTALLOXO-435 administered orally
Phase 1b: Cohort B1, B2, B4, and C1 LOXO-435 Monotherapy Dose Expansion
EXPERIMENTALLOXO-435 administered orally
Phase 1b: Cohort B3 LOXO-435 Plus Pembrolizumab
EXPERIMENTALLOXO-435 administered orally in combination with pembrolizumab administered intravenously (IV)
Phase 1b: Cohort B5 LOXO-435 Plus Pembrolizumab Plus Enfortumab Vedotin
EXPERIMENTALLOXO-435 administered orally in combination with pembrolizumab administered IV and enfortumab vedotin administered IV
Interventions
Oral
IV
Eligibility Criteria
You may qualify if:
- 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
- +5 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (82)
University of Arizona - Cancer Center
Tucson, Arizona, 85719, United States
City of Hope
Duarte, California, 91010, United States
University of California, Los Angeles (UCLA) - Division of Hematology-Oncology
Los Angeles, California, 90095, United States
University of California - Irvine
Orange, California, 92868, United States
University of California (UC) Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Stanford Medicine Cancer Center
Stanford, California, 94305, United States
Advent Health
Orlando, Florida, 32804, United States
Emory University Hospital
Atlanta, Georgia, 30322, United States
The University of Chicago Medical Center (UCMC)
Chicago, Illinois, 60637, United States
Indiana University (IU) Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202, United States
Mary Bird Perkins Cancer Center
Baton Rouge, Louisiana, 70809, United States
Ochsner Clinic Foundation
New Orleans, Louisiana, 70121, United States
Johns Hopkins Kimmel Cancer Center
Baltimore, Maryland, 21231-2410, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Washington University in St. Louis
St Louis, Missouri, 63108, United States
New York University (NYU)
New York, New York, 10016, United States
Weill Cornell Medicine
New York, New York, 10021, United States
Icahn School of Medicine at Mount Sinai
New York, New York, 10029, United States
Columbia University
New York, New York, 10032, United States
David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
University of Rochester - Wilmot Cancer Institute
Rochester, New York, 14642, United States
Montefiore Medical Center
The Bronx, New York, 10467, United States
University of North Carolina (UNC) - Chapel Hill
Chapel Hill, North Carolina, 27599, United States
University of Cincinnati Medical Center (UCMC)
Cincinnati, Ohio, 45267, United States
The Ohio State University (OSU)
Columbus, Ohio, 43210, United States
University of Oklahoma - Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Penn Medicine Lancaster General Hospital - Ann B. Barshinger Cancer Institute
Lancaster, Pennsylvania, 17601, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107, United States
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213, United States
Carolina Urologic Research Center
Myrtle Beach, South Carolina, 29572, United States
Sarah Cannon and HCA Research Institute
Nashville, Tennessee, 37203, United States
Tennessee Oncology
Nashville, Tennessee, 37203, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37212, United States
University of Texas Southwestern
Dallas, Texas, 75244, United States
Texas Oncology, P.A
Dallas, Texas, 75251, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
University of Utah
Salt Lake City, Utah, 84132, United States
University of Vermont Medical Center
Burlington, Vermont, 05401, United States
St Vincent's Hospital
Darlinghurst, NSW 2010, Australia
Calvary Mater Newcastle
Hunter Region, NSW, 2310, Australia
GenesisCare North Shore
St Leonards, 2065, Australia
Macquarie University
Sydney, 2109, Australia
Princess Margaret Hospital
Toronto, M5G 2M9, Canada
British Columbia Cancer Agency
Vancouver, V5Z 1J3, Canada
Beijing Cancer hospital
Beijing, 100142, China
Beijing Hospital
Beijing, 100730, China
Sun Yat-Sen University- Cancer Center
Guangdong, 510060, China
Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
Hangzhou, 310002, China
Renji Hospital, Shanghai Jiaotong University School of Medicine
Shanghai, 200000, China
Tianjin Medical University Cancer Institute & Hospital
Tianjin, 300060, China
The First Affiliated Hospital of Xi'an Jiaotong University
Xi'an, 710061, China
Zhejiang Provincial People's Hospital
Zhejiang, 310003, China
Institut Bergonie
Bordeaux, 33076, France
Centre Leon Berard
Lyon, 69373, France
Institut Gustave Roussy
Villejuif, 94805, France
Klinikum der Technischen Universitaet Muenchen (TUM Klinikum)
München, 81675, Germany
Universitaetsklinikum Tuebingen
Tübingen, 72016, Germany
Rabin Medical Center, Beilinson Hospital
Petah Tikva, 49100, Israel
Sheba Medical Center
Tel Litwinsky, 5265601, Israel
IRCCS Ospedale San Raffaele
Milan, 20132, Italy
UOC Fase I - Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
Roma, 00168, Italy
National Cancer Center Hospital East
Chiba, 277-8577, Japan
Aichi Cancer Center Hospital
Nagoya, 464-8681, Japan
National Cancer Center Hospital
Tokyo, 104-0045, Japan
Cancer Institute Hospital of JFCR
Tokyo, 135-8550, Japan
Erasmus MC
GE Rotterdam, 3015, Netherlands
Haukeland University Hospital
Bergen, 5021, Norway
Oslo University Hospital
Oslo, 0450, Norway
Seoul National University Hospital
Seoul, 03080, South Korea
Severance Hospital, Yonsei University Health System
Seoul, 03722, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
Institut Catala d'Oncologia - L'Hospitalet
Barcelona, 08908, Spain
Fundacion MD Anderson International Espana
Madrid, 28033, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
South Texas Accelerated Research Therapeutics (START) Madrid - CIOCC
Madrid, 28050, Spain
Hospital Universitario Marques De Valdecilla
Santander, 39008, Spain
The Christie NHS Foundation Trust
Manchester, M20 4BX, United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield, S10 2SB, United Kingdom
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- 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
Central Study Contacts
Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
CONTACT
Physicians interested in becoming principal investigators please contact
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Masking Details
- Cohort A2 is randomized
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 7, 2022
First Posted
November 14, 2022
Study Start
January 12, 2023
Primary Completion (Estimated)
June 1, 2027
Study Completion (Estimated)
June 1, 2027
Last Updated
May 19, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will not share