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NCT05614739PHASE1Recruiting

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

Eli Lilly and Company

Start Date

1/12/2023

Completion Date

6/1/2027

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.

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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

Interventions

DRUG

LOXO-435

DRUG

Pembrolizumab

DRUG

enfortumab vedotin

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Conditions

Urinary Bladder NeoplasmsNeoplasm MetastasisUreteral Neoplasms

Locations

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