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

April 3, 2024 updated by: Eli Lilly and Company

An Open-Label, Multicenter Study of LOXO-435 (LY3866288) In Advanced Solid Tumor Malignancies With FGFR3 Alterations

The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-435. 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 1a/b study in participants with FGFR3-altered advanced solid tumors, including metastatic urothelial cancer (UC). The study will be conducted in 2 phases: Dose escalation and dose optimization (1a) and dose expansion (1b). Phase 1a will include up to 2 cohorts to assess safety, tolerability, and pharmacokinetics of LOXO-435 to determine the recommended phase 2 dose (RP2D) (or optimal dose). Phase 1b will include 4 dose expansion cohorts of participants with prespecified activating FGFR3 alterations to evaluate the efficacy and safety of LOXO-435 at the RP2D. Cohort B will enroll pts with metastatic UC and includes three cohorts to evaluate LOXO-435 as monotherapy (B1, B2) and in combination with pembrolizumab (B3). Cohort C will enroll pts with non-UC advanced solid tumors and includes a cohort to evaluate LOXO-435 as monotherapy (C1).

Study Type

Interventional

Enrollment (Estimated)

180

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

Study Locations

  • Australia
      • Darlinghurst, Australia, NSW 2010
        • Recruiting
        • Kinghorn Cancer Centre
        • Contact:
          • Phone Number: 855-569-6305
    • New South Wales
      • Saint Leonards, New South Wales, Australia, 2065
        • Recruiting
        • GenesisCare North Shore
        • Contact:
          • Phone Number: 855-569-6305
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 1J3
        • Recruiting
        • British Columbia Cancer Agency
        • Contact:
          • Phone Number: 855-569-6305
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Recruiting
        • Princess Margaret Hospital
  • France
      • Lyon, France, 69008
        • Recruiting
        • Centre Leon Berard
        • Contact:
          • Phone Number: 855-569-6305
  • Germany
      • München, Germany, 81675
        • Recruiting
        • Klinikum rechts der Isar de Technischen Universitaet Muenchen
      • Tuebingen, Germany, 72076
        • Recruiting
        • Universitaetsklinikum Tuebingen
        • Contact:
          • Phone Number: 855-569-6305
  • Japan
      • Chiba, Japan, 277-8577
        • Recruiting
        • National Cancer Center Hospital East
        • Contact:
          • Phone Number: 855-569-6305
      • Tokyo, Japan, 135-8550
        • Recruiting
        • The Cancer Institute Hospital of JFCR
        • Contact:
          • Phone Number: 855-569-6305
    • Aichi
      • Nagoya, Aichi, Japan, 464-8681
        • Recruiting
        • Aichi Cancer Center Hospital
        • Contact:
          • Phone Number: 855-569-6305
    • Tokyo
      • Chuo Ku, Tokyo, Japan, 104-0045
        • Recruiting
        • National Cancer Center Hospital
        • Contact:
          • Phone Number: 855-569-6305
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03080
        • Recruiting
        • Seoul National University Hospital
        • Contact:
          • Phone Number: 855-569-6305
      • Seoul, Korea, Republic of, 06351
        • Recruiting
        • Samsung Medical Center
        • Contact:
          • Phone Number: 855-569-6305
      • Seoul, Korea, Republic of, 03722
        • Recruiting
        • Severance Hospital, Yonsei University Health System
        • Contact:
          • Phone Number: 855-569-6305
    • Seoul
      • Songpa-gu, Seoul, Korea, Republic of, 05505
        • Recruiting
        • Asan Medical Center
        • Contact:
          • Phone Number: 855-569-6305
  • Netherlands
      • Rotterdam, Netherlands, 3015 GD
        • Not yet recruiting
        • Erasmus MC
  • Norway
      • Bergen, Norway, 5021
        • Recruiting
        • Haukeland University
  • Spain
      • Madrid, Spain, 28041
        • Recruiting
        • Hospital Universitario 12 de Octubre
        • Contact:
          • Phone Number: 855-569-6305
      • Madrid, Spain, 28050
        • Not yet recruiting
        • South Texas Accelerated Research Therapeutics (START) Madrid
      • Santander, Spain, 39008
        • Recruiting
        • Hospital Universitario Marques de Valdecilla
  • United Kingdom
      • Manchester, United Kingdom, M20 4BX
        • Recruiting
        • The Christie NHS Foundation Trust
  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope Medical Center
        • Contact:
          • Phone Number: 855-569-6305
      • Santa Monica, California, United States, 90404
        • Recruiting
        • University of California Los Angeles
        • Contact:
          • Phone Number: 855-569-6305
    • Florida
      • Orlando, Florida, United States, 32804
        • Recruiting
        • Advent Health
        • Contact:
          • Phone Number: 855-569-6305
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University
        • Contact:
          • Phone Number: 855-569-6305
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • The University of Chicago Medical Center
    • 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:
          • Phone Number: 855-569-6305
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Barbara Ann Karmanos Cancer Institute
        • Contact:
          • Phone Number: 855-569-6305
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Contact:
          • Phone Number: 855-569-6305
    • New York
      • New York, New York, United States, 10029
        • Recruiting
        • Icahn School of Medicine at Mount Sinai
        • Contact:
          • Phone Number: 855-569-6305
      • New York, New York, United States, 10016
        • Recruiting
        • New York University
        • Contact:
          • Phone Number: 855-569-6305
      • 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
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7305
        • Recruiting
        • University of North Carolina at Chapel Hill
        • Contact:
          • Phone Number: 855-569-6305
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma Health Sciences Center
        • Contact:
          • Phone Number: 855-569-6305
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • University of Pennsylvania
        • Contact:
          • Phone Number: 855-569-6305
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • UPMC Hillman Cancer Center
        • Contact:
          • Phone Number: 855-569-6305
    • South Carolina
      • Myrtle Beach, South Carolina, United States, 29572
        • Recruiting
        • Carolina Urologic Research Center
        • Contact:
          • Phone Number: 855-569-6305
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Sarah Cannon and HCA Research Institute
        • Contact:
          • Phone Number: 855-569-6305
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • University of Texas Southwestern Medical Center
        • Contact:
          • Phone Number: 855-569-6305
      • Houston, Texas, United States, 77030-4009
        • Recruiting
        • Md Anderson Cancer Center
        • Contact:
          • Phone Number: 855-569-6305
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • Recruiting
        • University Of Utah
        • Contact:
          • Phone Number: 855-569-6305

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 (Dose Escalation): Presence of an alteration in FGFR3 or its ligands.
    • Cohort A2 (Dose Optimization): Histological diagnosis of urothelial cancer (UC) that is locally advanced or metastatic with a qualifying FGFR3 alteration.
    • Cohorts B1, B2 and B3 (Dose Expansion): Histological diagnosis of urothelial cancer that is locally advanced or metastatic with a prespecified activating FGFR3 alteration.
    • Cohort C (Dose Expansion): Must have histological diagnosis of a non-urothelial solid tumor malignancy that is locally advanced or metastatic with a prespecified activating FGFR3 alteration.

  • Measurability of disease:

    • Cohort A1: Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1)
    • Cohorts A2, B1, B2, B3, and C1: Measurable disease required as defined by RECIST v1.1
  • Have adequate archival tumor tissue sample available or undergo a screening biopsy if allowed per country-specific regulations.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

  • 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/B1/B2/B3: Participants must have received at least one prior regimen in the advanced or metastatic setting. There is no restriction on number of prior therapies.

  • FGFR inhibitor specific requirements:

    • Cohort A1/A2: Prior FGFR inhibitor treatment is permitted, but not required.
    • Cohort B1: Participants must have been previously treated with a FGFR inhibitor.
    • Cohort B2, B3, C1: Participants must be FGFR inhibitor naïve.

Exclusion Criteria:

  • Participants with primary central nervous system (CNS) malignancy.
  • Known or suspected history of uncontrolled CNS metastases.
  • Current evidence of corneal keratopathy or retinal disorder.
  • Have a history and/or current evidence of extensive tissue calcification.
  • 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 1b: Cohort B1 LOXO-435 Monotherapy Dose Expansion
LOXO-435 administered orally to participants with FGFR3-altered advanced urothelial carcinoma who were previously treated with an FGFR inhibitor.
Drug: LOXO-435
Oral
Other Names:
  • LY3866288
Experimental: Phase 1b: Cohort B2 LOXO-435 Monotherapy Dose Expansion
LOXO-435 administered orally to participants with FGFR3-altered advanced urothelial carcinoma who have not received a prior FGFR inhibitor.
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) to participants with FGFR3-altered advanced urothelial carcinoma who have not received a prior FGFR inhibitor.
Drug: Pembrolizumab
IV
Other Names:
  • KEYTRUDA®
Drug: LOXO-435
Oral
Other Names:
  • LY3866288
Experimental: Phase 1b: Cohort C1 LOXO-435 Monotherapy Dose Expansion
LOXO-435 administered orally to participants with advanced solid tumors who have not received a prior FGFR inhibitor.
Drug: LOXO-435
Oral
Other Names:
  • LY3866288
Experimental: Phase 1a: Cohort A1 LOXO-435 Monotherapy Dose Escalation
LOXO-435 administered orally to participants with FGFR3-altered advanced solid tumors.
Drug: LOXO-435
Oral
Other Names:
  • LY3866288
Experimental: Phase 1a: Cohort A2 LOXO-435 Monotherapy Dose Optimization
LOXO-435 administered orally to participants with FGFR3-altered advanced urothelial carcinoma. (Cohort to be implemented as needed, based on Sponsor's discretion.)
Drug: LOXO-435
Oral
Other Names:
  • LY3866288

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 phase 2 dose (RP2D)/optimal 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

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

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
Loxo Oncology, Inc.

Investigators

  • Study Director: Ryan Widau, PhD, Loxo Oncology, Inc.

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, 2025

Study Completion (Estimated)

June 1, 2025

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)

April 5, 2024

Last Update Submitted That Met QC Criteria

April 3, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LOXO-FG3-22001
  • J4G-OX-JZVA (Other Identifier: Eli Lilly and Company)
  • 2022-502755-59-00 (Other Identifier: EU CTR #)
  • KEYNOTE-F35 (Other Identifier: Merck Sharp & Dohme, LLC)
  • MK-3475-F35 (Other Identifier: Merck Sharp & Dohme, LLC)

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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