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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04526106




Registration number
NCT04526106
Ethics application status
Date submitted
7/08/2020
Date registered
25/08/2020
Date last updated
5/03/2024

Titles & IDs
Public title
REFOCUS: A First-in-Human Study of Highly Selective FGFR2 Inhibitor, RLY-4008, in Patients With ICC and Other Advanced Solid Tumors
Scientific title
A First-in-Human Study of Highly Selective FGFR2 Inhibitor, RLY-4008, in Patients With Intrahepatic Cholangiocarcinoma (ICC) and Other Advanced Solid Tumors
Secondary ID [1] 0 0
RLY-4008-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
FGFR2 Amplification 0 0
FGFR2 Gene Mutation 0 0
FGFR2 Gene Fusion/Rearrangement 0 0
FGFR2 Gene Translocation 0 0
FGFR2 Gene Activation 0 0
Intrahepatic Cholangiocarcinoma 0 0
Cholangiocarcinoma 0 0
Other Solid Tumors, Adult 0 0
Condition category
Condition code
Cancer 0 0 0 0
Biliary tree (gall bladder and bile duct)
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - RLY-4008

Experimental: Part 1: Dose Escalation - Multiple doses of RLY-4008 for oral administration.

Experimental: Part 2: Dose Expansion - Oral dose of RLY-4008 as determined during Part 1 Dose Escalation.

Experimental: Part 3: Extension - Oral dose of RLY-4008 as determined during Part 1 Dose Escalation.


Treatment: Drugs: RLY-4008
RLY-4008 is an oral inhibitor of FGFR2
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Determination of maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RLY-4008
Timepoint [1] 0 0
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
Primary outcome [2] 0 0
Part 1: Number of patients with adverse events and serious adverse events
Timepoint [2] 0 0
Every cycle (4-week cycles) until study discontinuation, approximately 24 months
Primary outcome [3] 0 0
Part 2 and Part 3: Objective Response Rate (ORR) assessed by Independent Review Committee per RECIST v1.1
Timepoint [3] 0 0
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 [1] 0 0
Part 1: FGFR2 gene status in plasma circulating tumor deoxyribonucleic acid (ctDNA) and tumor tissue
Timepoint [1] 0 0
Every cycle (4-week cycles) through Cycle 3 and every other cycle thereafter until study discontinuation, approximately 24 months
Secondary outcome [2] 0 0
Part 1: Duration of Response (DOR) assessed by Investigator per RECIST v1.1
Timepoint [2] 0 0
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 [3] 0 0
Part 1: Disease Control Rate (DCR) as assessed by Investigator per RECIST v1.1
Timepoint [3] 0 0
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 [4] 0 0
Part 1, Part 2, and Part 3: Objective Response Rate (ORR) as assessed by Investigator per RECIST v1.1
Timepoint [4] 0 0
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 [5] 0 0
Pharmacokinetic parameters including maximum plasma drug concentration (Cmax)
Timepoint [5] 0 0
Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through Cycle 4 (4-week cycles)
Secondary outcome [6] 0 0
Pharmacokinetic parameters including area under the plasma concentration versus time curve (AUC)
Timepoint [6] 0 0
Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through Cycle 4 (4-week cycles)
Secondary outcome [7] 0 0
Pharmacokinetic parameters including half-life (t1/2)
Timepoint [7] 0 0
Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through Cycle 4 (4-week cycles)
Secondary outcome [8] 0 0
Part 1: Pharmacodynamic parameters including changes in fibroblast growth factor 23 (FGF-23)
Timepoint [8] 0 0
Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months
Secondary outcome [9] 0 0
Part 1: Pharmacodynamic parameters including changes in carcinoembryonic antigen (CEA)
Timepoint [9] 0 0
Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months
Secondary outcome [10] 0 0
Part 1: Pharmacodynamic parameters including changes in cancer antigen 19-9 (CA 19-9)
Timepoint [10] 0 0
Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months
Secondary outcome [11] 0 0
Part 2 and Part 3: Duration of response (DOR) assessed by Investigator and Independent Review Committee per RECIST v1.1
Timepoint [11] 0 0
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 [12] 0 0
Part 2 and Part 3: Progression-free survival (PFS) assessed by Investigator and Independent Review Committee per RECIST v1.1
Timepoint [12] 0 0
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 [13] 0 0
Part 2 and Part 3: Disease control rate (DCR) assessed by Investigator and Independent Review Committee per RECIST v1.1
Timepoint [13] 0 0
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 [14] 0 0
Part 2 and Part 3:Overall survival (OS)
Timepoint [14] 0 0
Up to approximately 36 months.
Secondary outcome [15] 0 0
Part 2 and Part 3:Change from baseline in quality of life as assessed by EORTC QLQ-C30
Timepoint [15] 0 0
Approximately every 4 weeks during treatment, approximately 24 months
Secondary outcome [16] 0 0
Part 2 and Part 3:Dose intensity
Timepoint [16] 0 0
Every 28-day cycle until end of treatment, approximately 24 months.
Secondary outcome [17] 0 0
Part 2 and Part 3: Number of patients with dose interruptions
Timepoint [17] 0 0
Every 28-day cycle until end of treatment, approximately 24 months.
Secondary outcome [18] 0 0
Part 2 and Part 3: Number of patients with dose reductions
Timepoint [18] 0 0
Every 28-day cycle until end of treatment, approximately 24 months.
Secondary outcome [19] 0 0
Part 2 and Part 3: Number of patients with dose discontinuations
Timepoint [19] 0 0
Every 28-day cycle until end of treatment, approximately 24 months.
Secondary outcome [20] 0 0
Part 2 and Part 3: Correlation between FGFR2 genotype by central tissue assessment and antitumor response, as measured by ORR
Timepoint [20] 0 0
Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months

Eligibility
Key inclusion criteria
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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/09/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2024
Actual
Sample size
Target
540
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
St. Vincent's Hosptial Sydney - Darlinghurst
Recruitment hospital [2] 0 0
Linear Clinical Research Ltd - Nedlands
Recruitment hospital [3] 0 0
Icon Cancer Care South Brisbane - South Brisbane,
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
6009 - Nedlands
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane,
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Minnesota
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Utah
Country [15] 0 0
United States of America
State/province [15] 0 0
Washington
Country [16] 0 0
France
State/province [16] 0 0
Bordeaux
Country [17] 0 0
France
State/province [17] 0 0
Dijon
Country [18] 0 0
France
State/province [18] 0 0
Lyon
Country [19] 0 0
France
State/province [19] 0 0
Nice
Country [20] 0 0
France
State/province [20] 0 0
Paris
Country [21] 0 0
Germany
State/province [21] 0 0
Hannover
Country [22] 0 0
Germany
State/province [22] 0 0
Heidelberg
Country [23] 0 0
Germany
State/province [23] 0 0
Munich
Country [24] 0 0
Hong Kong
State/province [24] 0 0
Hong Kong
Country [25] 0 0
Italy
State/province [25] 0 0
Milano
Country [26] 0 0
Italy
State/province [26] 0 0
Roma
Country [27] 0 0
Korea, Republic of
State/province [27] 0 0
Seoul
Country [28] 0 0
Netherlands
State/province [28] 0 0
Amsterdam
Country [29] 0 0
Netherlands
State/province [29] 0 0
Rotterdam
Country [30] 0 0
Singapore
State/province [30] 0 0
Singapore
Country [31] 0 0
Spain
State/province [31] 0 0
Barcelona
Country [32] 0 0
Spain
State/province [32] 0 0
Madrid
Country [33] 0 0
Spain
State/province [33] 0 0
Pamplona
Country [34] 0 0
Spain
State/province [34] 0 0
Valencia
Country [35] 0 0
Sweden
State/province [35] 0 0
Stockholm
Country [36] 0 0
Taiwan
State/province [36] 0 0
Taichung
Country [37] 0 0
United Kingdom
State/province [37] 0 0
London
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Relay Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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 3 parts: a dose
escalation (Part 1), a dose expansion (Part 2), and an extension (Part 3).
Trial website
https://clinicaltrials.gov/ct2/show/NCT04526106
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04526106