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

NCT04526106 | Completed Phase 1 FDA Drug

• 1 other identifier: RLY-4008-101
• Study Type: interventional
• Target: 490
• Locations: 13 countries
• Sites: 48

Brief Summary

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 4 parts: a dose escalation (Part 1), a dose expansion (Part 2), and an extension (Part 3) and a rollover (Part 4).

Conditions

FGFR2 Amplification; FGFR2 Gene Mutation; FGFR2 Gene Fusion/Rearrangement; FGFR2 Gene Translocation; FGFR2 Gene Activation; Intrahepatic Cholangiocarcinoma; Cholangiocarcinoma; Other Solid Tumors, Adult

Outcome Measures

Primary Outcomes (6)

• Part 1 and Part 4: Number of patients with adverse events and serious adverse events

  Every cycle (4-week cycles) until study discontinuation, approximately 24 months

• Part 1: Determination of maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RLY-4008

  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 2 and Part 3: Objective Response Rate (ORR) assessed by Independent Review Committee per RECIST v1.1

  Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months

• Part 4: Number of patients with dose interruptions

  Every 28-day cycle until end of treatment, approximately 24 months.

• Part 4: Number of patients with dose reductions

  Every 28-day cycle until end of treatment, approximately 24 months.

• Part 4: Number of patients with dose discontinuations

  Every 28-day cycle until end of treatment, approximately 24 months.

Secondary Outcomes (20)

• Part 1: FGFR2 gene status in plasma circulating tumor deoxyribonucleic acid (ctDNA) and tumor tissue

  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

  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

  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

  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)

  Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through Cycle 4 (4-week cycles)

Study Arms (4)

Part 1: Dose Escalation

EXPERIMENTAL

Multiple doses of RLY-4008 for oral administration.

Drug: RLY-4008

Part 2: Dose Expansion

EXPERIMENTAL

Oral dose of RLY-4008 as determined during Part 1 Dose Escalation.

Drug: RLY-4008

Part 3: Extension

EXPERIMENTAL

Oral dose of RLY-4008 as determined during Part 1 Dose Escalation.

Drug: RLY-4008

Part 4: Rollover

EXPERIMENTAL

Oral dose of RLY-4008 as determined during Part 1 Dose Escalation.

Drug: RLY-4008

Interventions

RLY-4008 DRUG

RLY-4008 is an oral inhibitor of FGFR2

Part 1: Dose Escalation; Part 2: Dose Expansion; Part 3: Extension; Part 4: Rollover

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• Parts 1, 2, and 3
• 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
• Part 4:
• Patient has permanently discontinued treatment with RLY-4008 for any reason before enrolling into Part 4.

Sponsors & Collaborators

• Elevar Therapeutics: lead

Study Sites (48)

The University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Taussig Cancer Institute Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Texas Oncology

Dallas, Texas, 75246, United States

Location

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, 84112, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

St. Vincent's Hosptial Sydney

Darlinghurst, 2010, Australia

Location

Linear Clinical Research Ltd

Nedlands, 6009, Australia

Location

Icon Cancer Care South Brisbane

South Brisbane, 4101, Australia

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Centre Georges François Leclerc

Dijon, 21079, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Gustave Roussy Cancer Campus

Paris, 94805, France

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

LMU Klinikum, Campus Grosshadern

Munich, 81377, Germany

Location

Queen Mary Hospital

Hong Kong, 999077, Hong Kong

Location

Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Netherlands Cancer institute

Amsterdam, 1066 CX, Netherlands

Location

Erasmus MC

Rotterdam, 3015 GD, Netherlands

Location

National Cancer Center Singapore

Singapore, 169610, Singapore

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

START Barcelona-Hospital HM Nou Delfos

Barcelona, 08023, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Fundación Jiménez Díaz- START MADRID

Madrid, 28040, Spain

Location

Hospital Universitario HM Sanchinarro-START MADRID-CIOCC

Madrid, 28050, Spain

Location

Clinica de Universidad de Navarra

Pamplona, 31008, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Karolinska University Hospital

Stockholm, 17176, Sweden

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

Guy's Hospital

London, SE1 9RT, United Kingdom

Location

Sarah Cannon Research Institute UK

London, W1G 6AD, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, W1T 7HA, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Cholangiocarcinoma

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 (multiple ascending doses): • Unresectable or metastatic CCA or other unresectable or metastatic solid tumor Part 2 (RP2D determined in Part 1): * Group 1: CCA patients w/ an FGFR2 fusion previously treated w/ an FGFRi treatment * Group 2: CCA patients w/ an FGFR2 fusion w/ prior chemotherapy but no prior FGFRi treatment * Group 3: Non-CCA patients w/ an FGFR2 fusion and no prior FGFRi * Group 4: Non-CCA patients w/ an FGFR2 amplification and no prior FGFRi treatment * Group 5: Non-CCA patients w/ an FGFR2 mutation and no prior FGFRi treatment * Group 6: CCA patients w/ an FGFR2 fusion with no prior chemotherapy and no prior FGFRi treatment * Group 7: CCA patients w/ an FGFR2 mutation or amplification and no prior FGFRi treatment Part 3 (Extension of Part 2, Group 2): • CCA patients w/ an FGFR2 fusion with prior chemotherapy but no prior FGFRi treatment Part 4 (Rollover): • Ongoing Parts 1, 2, and 3 patients enrolled on study and receiving RLY-4008

Study Record Dates

• First Submitted: August 7, 2020
• First Posted: August 25, 2020
• Study Start: September 2, 2020
• Primary Completion: September 5, 2025
• Study Completion: September 5, 2025
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3); DE (3); NL (2); GB (4); HK (1); SG (1); US (18); IT (1); FR (4); TW (1); KR (3); ES (6); SE (1)