FGFR2 AmplificationPhase 1/2NCT04526106
REFOCUS: A First-in-Human Study of Highly Selective FGFR2 Inhibitor, RLY-4008, in Patients With ICC and Other Advanced Solid Tumors
A Phase 1/2 study testing RLY-4008 in people with FGFR2 Amplification and FGFR2 Gene Mutation, run by Elevar Therapeutics at 48 sites in 13 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- FGFR2 Amplification, FGFR2 Gene Mutation, FGFR2 Gene Fusion/Rearrangement
- What is being tested?
- RLY-4008
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 490 participants
- Where
- 48 sitesin 13 countries
- Study dates
- 2 Sep 2020to 5 Sep 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 18Show fewer
- 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:
- o CCA patients with an FGFR2 fusion with prior chemotherapy but not previously treated with an FGFRi
- Part 4:
- Patient is receiving RLY-4008 on RLY-4008-101 study and benefiting from treatment as assessed by the investigator.
Who cannot join
- 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
Show all 9Show fewer
- 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.
Trial locations and contacts
48 sites in 13 countries.
48 sites in 13 countries
United States18 sites
University of Michigan
Ann Arbor, Michigan, 48109
Winship Cancer Institute, Emory University
Atlanta, Georgia, 30322
The University of Alabama at Birmingham
Birmingham, Alabama, 35294
Massachusetts General Hospital
Boston, Massachusetts, 02114
University of Chicago Medical Center
Chicago, Illinois, 60637
Taussig Cancer Institute Cleveland Clinic
Cleveland, Ohio, 44195
Texas Oncology
Dallas, Texas, 75246
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, 77030
Mayo Clinic
Jacksonville, Florida, 32224
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Mayo Clinic
Phoenix, Arizona, 85054
Mayo Clinic
Rochester, Minnesota, 55905
Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, 84112
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94158
Virginia Mason Medical Center
Seattle, Washington, 98101
Moffitt Cancer Center
Tampa, Florida, 33612
Spain6 sites
START Barcelona-Hospital HM Nou Delfos
Barcelona, 08023
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Universitario Fundación Jiménez Díaz- START MADRID
Madrid, 28040
Hospital Universitario HM Sanchinarro-START MADRID-CIOCC
Madrid, 28050
Clinica de Universidad de Navarra
Pamplona, 31008
Hospital Clínico Universitario de Valencia
Valencia, 46010
France4 sites
Institut Bergonie
Bordeaux, 33076
Centre Georges François Leclerc
Dijon, 21079
Centre Leon Berard
Lyon, 69373
Gustave Roussy Cancer Campus
Paris, 94805
United Kingdom4 sites
Guy's Hospital
London, SE1 9RT
Sarah Cannon Research Institute UK
London, W1G 6AD
University College London Hospitals NHS Foundation Trust
London, W1T 7HA
The Christie NHS Foundation Trust
Manchester, M20 4BX
Australia3 sites
St. Vincent's Hosptial Sydney
Darlinghurst, 2010
Linear Clinical Research Ltd
Nedlands, 6009
Icon Cancer Care South Brisbane
South Brisbane, 4101
Germany3 sites
Medizinische Hochschule Hannover
Hanover, 30625
Universitätsklinikum Heidelberg
Heidelberg, 69120
LMU Klinikum, Campus Grosshadern
Munich, 81377
South Korea3 sites
Seoul National University Hospital
Seoul, 03080
Asan Medical Center
Seoul, 05505
Samsung Medical Center
Seoul, 06351
Netherlands2 sites
Netherlands Cancer institute
Amsterdam, 1066 CX
Erasmus MC
Rotterdam, 3015 GD
About this study
Official title: 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 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
- Being tested
- RLY-4008
- Medical subject headings
- Cholangiocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RLY-4008Drug
RLY-4008 is an oral inhibitor of FGFR2
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Dose Escalation | Experimental | Multiple doses of RLY-4008 for oral administration. Receives: Drug: RLY-4008 |
| Part 2: Dose Expansion | Experimental | Oral dose of RLY-4008 as determined during Part 1 Dose Escalation. Receives: Drug: RLY-4008 |
| Part 3: Extension | Experimental | Oral dose of RLY-4008 as determined during Part 1 Dose Escalation. Receives: Drug: RLY-4008 |
| Part 4: Rollover | Experimental | Oral dose of RLY-4008 as determined during Part 1 Dose Escalation. Receives: Drug: RLY-4008 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1 and Part 4: Number of patients with adverse events and serious adverse events
Measured: 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
Measured: 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
Measured: 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
Measured: Every 28-day cycle until end of treatment, approximately 24 months.
Part 4: Number of patients with dose reductions
Measured: Every 28-day cycle until end of treatment, approximately 24 months.
Part 4: Number of patients with dose discontinuations
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: Up to approximately 36 months.
Part 2 and Part 3:Change from baseline in quality of life as assessed by EORTC QLQ-C30
Measured: Approximately every 4 weeks during treatment, approximately 24 months
Part 2 and Part 3:Dose intensity
Measured: Every 28-day cycle until end of treatment, approximately 24 months.
Part 2 and Part 3: Number of patients with dose interruptions
Measured: Every 28-day cycle until end of treatment, approximately 24 months.
Part 2 and Part 3: Number of patients with dose reductions
Measured: Every 28-day cycle until end of treatment, approximately 24 months.
Part 2 and Part 3: Number of patients with dose discontinuations
Measured: 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
Measured: Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2020
- Study start2 Sep 2020
- Primary completion5 Sep 2025
- Study completion5 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for FGFR2 AmplificationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 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
- Masking
- None (open label)
- Enrolment
- 490 participants (actual)
Sponsor and investigators
- Lead sponsor
- Elevar Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04526106
- Sponsor's protocol ID
- RLY-4008-101
- Status last verified
- Feb 2026
- First submitted
- 7 Aug 2020
- Last updated
- 27 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ellis H, Balasooriya ER, Varkaris A, Hajian B, Wan J, Shekhar M, Gritti I, Vijay V, Albertelli L, Piot S, Lau K, Kehlmann A, Chevalier N, Nugent FW, Zhen Y, Silveira VS, Sellers WR, Corcoran RB, Juric D, Bardeesy N. Mechanisms of clinical resistance to selective FGFR2 inhibition by lirafugratinib. Ann Oncol. 2026 Jun;37(6):798-812. doi: 10.1016/j.annonc.2026.01.004. Epub 2026 Jan 20.
PubMed 41571046
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A First-in-Human Study of Highly Selective FGFR2 Inhibitor, RLY-4008, in Patients With Intrahepatic Cholangiocarcinoma (ICC) and Other Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT04526106
- Acronym / sponsor ID
- RLY-4008-101
- Conditions
- FGFR2 Amplification, FGFR2 Gene Mutation, FGFR2 Gene Fusion/Rearrangement, FGFR2 Gene Translocation, FGFR2 Gene Activation, Intrahepatic Cholangiocarcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 490 participants (actual)
- Lead sponsor
- Elevar TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 2 Sep 2020 (actual)
- Primary completion
- 5 Sep 2025 (actual)
- Study completion
- 5 Sep 2025 (actual)
- First posted
- 25 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- 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
| Arm | Type | Receives |
|---|---|---|
| Part 1: Dose Escalation | Experimental | Drug: RLY-4008Multiple doses of RLY-4008 for oral administration. |
| Part 2: Dose Expansion | Experimental | Drug: RLY-4008Oral dose of RLY-4008 as determined during Part 1 Dose Escalation. |
| Part 3: Extension | Experimental | Drug: RLY-4008Oral dose of RLY-4008 as determined during Part 1 Dose Escalation. |
| Part 4: Rollover | Experimental | Drug: RLY-4008Oral dose of RLY-4008 as determined during Part 1 Dose Escalation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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
Key exclusion criteria (9 listed)
- Parts 1, 2, and 3
- Part 4:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RLY-4008RLY-4008 is an oral inhibitor of FGFR2 | Drug | Part 1: Dose Escalation, Part 2: Dose Expansion, Part 3: Extension, Part 4: Rollover |
Primary outcome
Part 1 and Part 4: Number of patients with adverse events and serious adverse events
Time frame: 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
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
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
Part 4: Number of patients with dose interruptions
Time frame: Every 28-day cycle until end of treatment, approximately 24 months.
Part 4: Number of patients with dose reductions
Time frame: Every 28-day cycle until end of treatment, approximately 24 months.
Part 4: Number of patients with dose discontinuations
Time frame: Every 28-day cycle until end of treatment, approximately 24 months.
20 secondary outcomes
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
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
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
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
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)
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)
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)
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
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
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
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
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
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
Part 2 and Part 3:Overall survival (OS)
Time frame: 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
Part 2 and Part 3:Dose intensity
Time frame: 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.
Part 2 and Part 3: Number of patients with dose reductions
Time frame: 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.
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2026.
- Derived from this study: PubMed 41571046Ellis H, Balasooriya ER, Varkaris A, Hajian B, Wan J, Shekhar M, Gritti I, Vijay V, Albertelli L, Piot S, Lau K, Kehlmann A, Chevalier N, Nugent FW, Zhen Y, Silveira VS, Sellers WR, Corcoran RB, Juric D, Bardeesy N. Mechanisms of clinical resistance to selective FGFR2 inhibition by lirafugratinib. Ann Oncol. 2026 Jun;37(6):798-812. doi: 10.1016/j.annonc.2026.01.004. Epub 2026 Jan 20.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
48 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing RLY-4008 in people with FGFR2 Amplification and FGFR2 Gene Mutation, run by Elevar Therapeutics at 48 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 48 sites in United States, Spain, France, United Kingdom, Australia and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1 and Part 4: Number of patients with adverse events and serious adverse events (time frame: Every cycle (4-week cycles) until study discontinuation, approximately 24 months). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04526106, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2026.