REFOCUS: A First-in-Human Study of Highly Selective FGFR2 Inhibitor, RLY-4008, in Patients With ICC and Other Advanced Solid Tumors

March 1, 2024 updated by: Relay Therapeutics, Inc.

A First-in-Human Study of Highly Selective FGFR2 Inhibitor, RLY-4008, in Patients With Intrahepatic Cholangiocarcinoma (ICC) and Other Advanced Solid Tumors

This is a Phase 1/2, open-label, FIH study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PDy), and antineoplastic activity of RLY-4008, a potent and highly selective FGFR2 inhibitor, in patients with unresectable or metastatic cholangiocarcinoma (CCA) and other solid tumors. The study consists of 3 parts: a dose escalation (Part 1), a dose expansion (Part 2), and an extension (Part 3).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

540

Phase

  • Phase 2
  • 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 Locations

  • Australia
      • Darlinghurst, Australia, 2010
        • St. Vincent's Hosptial Sydney
      • Nedlands, Australia, 6009
        • Linear Clinical Research Ltd
      • South Brisbane,, Australia, 4101
        • Icon Cancer Care South Brisbane
  • France
      • Bordeaux, France, 33076
        • Institut Bergonié
      • Dijon, France, 21079
        • Centre Georges Francois Leclerc
      • Lyon, France, 69373
        • Centre Leon Berard
      • Nice, France, 06189
        • Centre Antoine Lacassagne
      • Paris, France, 94805
        • Gustave Roussy Cancer Campus
  • Germany
      • Hannover, Germany, 30625
        • Medizinische Hochschule Hannover
      • Heidelberg, Germany, 69120
        • Universitätsklinikum Heidelberg
      • Munich, Germany, 81377
        • LMU Klinikum, Campus Grosshadern
  • Hong Kong
      • Hong Kong, Hong Kong, 999077
        • Queen Mary Hospital
  • Italy
      • Milano, Italy, 20141
        • Istituto Europeo di Oncologia
      • Roma, Italy, 00144
        • Istituto Nazionale Tumori Regina Elena
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 05505
        • Asan Medical Center
      • Seoul, Korea, Republic of, 06351
        • Samsung Medical Center
  • Netherlands
      • Amsterdam, Netherlands, 1066 CX
        • Netherlands Cancer Institute
      • Rotterdam, Netherlands, 3015 GD
        • Erasmus MC
  • Singapore
      • Singapore, Singapore, 169610
        • National Cancer Center Singapore
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
      • Barcelona, Spain, 08023
        • START Barcelona-Hospital HM Nou Delfos
      • Madrid, Spain, 28040
        • Hospital Universitario Fundación Jiménez Díaz- START MADRID
      • Madrid, Spain, 28050
        • Hospital Universitario HM Sanchinarro-START MADRID-CIOCC
      • Pamplona, Spain, 31008
        • Clinica de Universidad de Navarra
      • Valencia, Spain, 46010
        • Hospital Clinico Universitario de Valencia
  • Sweden
      • Stockholm, Sweden, 17176
        • Karolinska University Hospital
  • Taiwan
      • Taichung, Taiwan, 40447
        • China Medical University Hospital
  • United Kingdom
      • London, United Kingdom, SE1 9RT
        • Guy's Hospital
      • London, United Kingdom, W1G 6AD
        • Sarah Cannon Research Institute UK
      • London, United Kingdom, W1T 7HA
        • University College London Hospitals NHS Foundation Trust
      • Manchester, United Kingdom, M20 4BX
        • The Christie NHS Foundation Trust
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • The University of Alabama at Birmingham
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic
    • California
      • Los Angeles, California, United States, 90033
        • USC Norris Comprehensive Cancer Center
      • San Francisco, California, United States, 94158
        • UCSF Helen Diller Family Comprehensive Cancer Center
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute, Emory University
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Taussig Cancer Institute Cleveland Clinic
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
    • Texas
      • Dallas, Texas, United States, 75246
        • Texas Oncology
      • Houston, Texas, United States, 77030
        • The University of Texas M.D. Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute, University of Utah
    • Washington
      • Seattle, Washington, United States, 98101
        • Virginia Mason 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

Key Inclusion Criteria

  • Histologically or cytologically confirmed unresectable or metastatic solid tumor
  • Documented FGFR2 gene fusion, mutation, or amplification per local testing of blood and/or tumor
  • Patient must have measurable disease per RECIST v1.1
  • Patient has ECOG performance status of 0-1
  • Patient must have disease that is refractory to standard therapy, disease that has not adequately responded to standard therapy, disease for which standard or curative therapy does not exist, or the patient must be intolerant to or have declined standard therapy

  • Part 2 dose expansion patients with Cholangiocarcinoma:

    • Group 1: CCA patients with an FGFR2 fusion previously treated with an FGFRi
    • Group 2: CCA patients with an FGFR2 fusion with prior chemotherapy but not previously treated with an FGFRi
    • Group 6: CCA patients with an FGFR2 fusion with no prior chemotherapy and not previously treated with an FGFRi. Prior adjuvant/neo-adjuvant treatment completed >6 months before enrollment is acceptable. Up to 2 cycles of palliative chemotherapy are allowed during screening
    • Group 7: CCA patients with an FGFR2 mutation or amplification and not previously treated with an FGFRi. Note: For Group 7, patients with confirmed diagnosis of unresectable or metastatic CCA with an FGFR2 fusion are not eligible.

  • Part 2 dose expansion patients with other solid tumors (NOT Cholangiocarcinoma):

    • Group 3: Non-CCA patients with an FGFR2 fusion and not previously treated with an FGFRi.
    • Group 4: Non-CCA patients with an FGFR2 amplification and not previously treated with an FGFRi.
    • Group 5: Non-CCA patients with an FGFR2 mutation and not previously treated with an FGFRi

  • Part 3 extension:

    • CCA patients with an FGFR2 fusion with prior chemotherapy but not previously treated with an FGFRi

Key Exclusion Criteria

  • Ongoing, clinically significant FGFRi-induced retinal detachment or an ongoing clinically significant corneal or retinal disorder
  • Patient does not have adequate organ function (defined in protocol)
  • Patient has active infection, including human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV) (defined in protocol). Patients with well-controlled HBV are eligible (defined in protocol).
  • QT interval corrected using Fridericia's formula (QTcF) > 480 msec or history of prolonged QT syndrome, Torsades de pointes or familial history of prolonged QT syndrome
  • Clinically significant, uncontrolled cardiovascular disease
  • CNS metastases or primary CNS tumor that is associated with progressive neurologic symptoms

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: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part 1: Dose Escalation
Multiple doses of RLY-4008 for oral administration.
Drug: RLY-4008
RLY-4008 is an oral inhibitor of FGFR2
Experimental: Part 2: Dose Expansion
Oral dose of RLY-4008 as determined during Part 1 Dose Escalation.
Drug: RLY-4008
RLY-4008 is an oral inhibitor of FGFR2
Experimental: Part 3: Extension
Oral dose of RLY-4008 as determined during Part 1 Dose Escalation.
Drug: RLY-4008
RLY-4008 is an oral inhibitor of FGFR2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Part 1: Determination of maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RLY-4008
Time Frame: Cycle 1 (4-week cycle) of treatment for MTD and at the end of every cycle (4-week cycles) for RP2D until study discontinuation, approximately 24 months
Cycle 1 (4-week cycle) of treatment for MTD and at the end of every cycle (4-week cycles) for RP2D until study discontinuation, approximately 24 months
Part 1: Number of patients with adverse events and serious adverse events
Time Frame: Every cycle (4-week cycles) until study discontinuation, approximately 24 months
Every cycle (4-week cycles) until study discontinuation, approximately 24 months
Part 2 and Part 3: Objective Response Rate (ORR) assessed by Independent Review Committee per RECIST v1.1
Time Frame: Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months
Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Part 1: FGFR2 gene status in plasma circulating tumor deoxyribonucleic acid (ctDNA) and tumor tissue
Time Frame: Every cycle (4-week cycles) through Cycle 3 and every other cycle thereafter until study discontinuation, approximately 24 months
Every cycle (4-week cycles) through Cycle 3 and every other cycle thereafter until study discontinuation, approximately 24 months
Part 1: Duration of Response (DOR) assessed by Investigator per RECIST v1.1
Time Frame: Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months
Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months
Part 1: Disease Control Rate (DCR) as assessed by Investigator per RECIST v1.1
Time Frame: Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months
Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months
Part 1, Part 2, and Part 3: Objective Response Rate (ORR) as assessed by Investigator per RECIST v1.1
Time Frame: Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months
Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months
Pharmacokinetic parameters including maximum plasma drug concentration (Cmax)
Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through Cycle 4 (4-week cycles)
Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through Cycle 4 (4-week cycles)
Pharmacokinetic parameters including area under the plasma concentration versus time curve (AUC)
Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through Cycle 4 (4-week cycles)
Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through Cycle 4 (4-week cycles)
Pharmacokinetic parameters including half-life (t1/2)
Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through Cycle 4 (4-week cycles)
Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through Cycle 4 (4-week cycles)
Part 1: Pharmacodynamic parameters including changes in fibroblast growth factor 23 (FGF-23)
Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months
Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months
Part 1: Pharmacodynamic parameters including changes in carcinoembryonic antigen (CEA)
Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months
Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months
Part 1: Pharmacodynamic parameters including changes in cancer antigen 19-9 (CA 19-9)
Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months
Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months
Part 2 and Part 3: Duration of response (DOR) assessed by Investigator and Independent Review Committee per RECIST v1.1
Time Frame: Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months
Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months
Part 2 and Part 3: Progression-free survival (PFS) assessed by Investigator and Independent Review Committee per RECIST v1.1
Time Frame: Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months
Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months
Part 2 and Part 3: Disease control rate (DCR) assessed by Investigator and Independent Review Committee per RECIST v1.1
Time Frame: Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months
Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months
Part 2 and Part 3:Overall survival (OS)
Time Frame: Up to approximately 36 months.
Up to approximately 36 months.
Part 2 and Part 3:Change from baseline in quality of life as assessed by EORTC QLQ-C30
Time Frame: Approximately every 4 weeks during treatment, approximately 24 months
Approximately every 4 weeks during treatment, approximately 24 months
Part 2 and Part 3:Dose intensity
Time Frame: Every 28-day cycle until end of treatment, approximately 24 months.
Every 28-day cycle until end of treatment, approximately 24 months.
Part 2 and Part 3: Number of patients with dose interruptions
Time Frame: Every 28-day cycle until end of treatment, approximately 24 months.
Every 28-day cycle until end of treatment, approximately 24 months.
Part 2 and Part 3: Number of patients with dose reductions
Time Frame: Every 28-day cycle until end of treatment, approximately 24 months.
Every 28-day cycle until end of treatment, approximately 24 months.
Part 2 and Part 3: Number of patients with dose discontinuations
Time Frame: Every 28-day cycle until end of treatment, approximately 24 months.
Every 28-day cycle until end of treatment, approximately 24 months.
Part 2 and Part 3: Correlation between FGFR2 genotype by central tissue assessment and antitumor response, as measured by ORR
Time Frame: Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months
Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months

Collaborators and Investigators

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

Sponsor

Relay Therapeutics, Inc.

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)

September 2, 2020

Primary Completion (Estimated)

June 1, 2024

Study Completion (Estimated)

October 1, 2024

Study Registration Dates

First Submitted

August 7, 2020

First Submitted That Met QC Criteria

August 20, 2020

First Posted (Actual)

August 25, 2020

Study Record Updates

Last Update Posted (Estimated)

March 5, 2024

Last Update Submitted That Met QC Criteria

March 1, 2024

Last Verified

October 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RLY-4008-101

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

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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