REFOCUS: A First-in-Human Study of Highly Selective FGFR2 Inhibitor, RLY-4008, in Patients With ICC and Other Advanced Solid Tumors
Study Details
Study Description
Brief Summary
This is a Phase 1/2, open-label, FIH study designed to evaluate the safety, tolerability, PK, PDy, and antineoplastic activity of RLY-4008, a potent and highly selective FGFR2 inhibitor, in patients with unresectable or metastatic 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).
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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
|
Outcome Measures
Primary Outcome Measures
- Objective Response Rate (ORR) assessed 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]
- 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]
- Number of patients with adverse events and serious adverse events [Every cycle (4-week cycles) until study discontinuation, approximately 24 months]
Secondary Outcome Measures
- Duration of Response (DOR) assessed 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]
- 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]
- Disease Control Rate (DCR) as assessed by 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 though Cycle 4 (4-week cycles)]
- Pharmacokinetic parameters including area under the plasma concentration versus time curve from time 0 to 24 hours postdose (AUC0-24) [Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle though Cycle 4 (4-week cycles)]
- Pharmacokinetic parameters including terminal elimination half-life (t1/2) [Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle though Cycle 4 (4-week cycles)]
- Pharmacodynamic parameters including changes in fibroblast growth factor 23 (FGF-23) [Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months]
- Pharmacodynamic parameters including changes in carcinoembryonic antigen (CEA) [Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months]
- Pharmacodynamic parameters including changes in cancer antigen 19-9 (CA 19-9) [Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months]
Eligibility Criteria
Criteria
Key Inclusion Criteria
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Histologically or cytologically confirmed unresectable or metastatic solid tumor
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Documented FGFR2 gene fusion, mutation, or amplification per local testing of blood and/or tumor
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Patient must have measurable disease per RECIST v1.1
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Patient has ECOG performance status of 0-1
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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 (except for Group 6, as defined below)
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Part 2 dose expansion patients with Cholangiocarcinoma:
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Group 1: CCA patients with an FGFR2 fusion previously treated with an FGFRi
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Group 2: CCA patients with an FGFR2 fusion with prior chemotherapy but not previously treated with an FGFRi
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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. A single cycle of palliative chemotherapy is allowed during screening
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Group 7: CCA patients with an FGFR2 mutation or amplification
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Part 2 dose expansion patients with other solid tumors (NOT Cholangiocarcinoma):
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Group 3: Non-CCA patients with an FGFR2 fusion
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Group 4: Non-CCA patients with an FGFR2 amplification
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Group 5: Non-CCA patients with an FGFR2 mutation
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Part 3 extension:
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CCA patients with an FGFR2 fusion with prior chemotherapy but not previously treated with an FGFRi
Key Exclusion Criteria
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Ongoing, clinically significant FGFRi-induced retinal detachment or an ongoing clinically significant corneal or retinal disorder
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Patient does not have adequate organ function (defined in protocol)
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Patient has active infection, including human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV) (defined in protocol)
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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
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Clinically significant, uncontrolled cardiovascular disease
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CNS metastases or primary CNS tumor that is associated with progressive neurologic symptoms
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Mayo Clinic | Phoenix | Arizona | United States | 85054 |
2 | USC Norris Comprehensive Cancer Center | Los Angeles | California | United States | 90033 |
3 | UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco | California | United States | 94158 |
4 | Mayo Clinic | Jacksonville | Florida | United States | 32224 |
5 | Moffitt Cancer Center | Tampa | Florida | United States | 33612 |
6 | University of Chicago Medical Center | Chicago | Illinois | United States | 60637 |
7 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
8 | University of Michigan | Ann Arbor | Michigan | United States | 48109 |
9 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
10 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
11 | Taussig Cancer Institute Cleveland Clinic | Cleveland | Ohio | United States | 44195 |
12 | Fox Chase Cancer Center | Philadelphia | Pennsylvania | United States | 19111 |
13 | Texas Oncology | Dallas | Texas | United States | 75246 |
14 | The University of Texas M.D. Anderson Cancer Center | Houston | Texas | United States | 77030 |
15 | Huntsman Cancer Institute, University of Utah | Salt Lake City | Utah | United States | 84112 |
16 | Virginia Mason Medical Center | Seattle | Washington | United States | 98101 |
17 | St. Vincent's Hosptial Sydney | Darlinghurst | Australia | 2010 | |
18 | Linear Clinical Research Ltd | Nedlands | Australia | 6009 | |
19 | Icon Cancer Care South Brisbane | South Brisbane, | Australia | 4101 | |
20 | Institut Bergonie | Bordeaux | France | 33076 | |
21 | Centre Georges François Leclerc | Dijon | France | 21079 | |
22 | Centre Leon Berard | Lyon | France | 69373 | |
23 | Gustave Roussy Cancer Campus | Paris | France | 94805 | |
24 | Queen Mary Hospital | Hong Kong | Hong Kong | 999077 | |
25 | IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori | Meldola | Italy | 47014 | |
26 | Istituto Europeo di Oncologia | Milano | Italy | 20141 | |
27 | Istituto Nazionale Tumori Regina Elena | Roma | Italy | 00144 | |
28 | Seoul National University Hospital | Seoul | Korea, Republic of | 03080 | |
29 | Asan Medical Center | Seoul | Korea, Republic of | 05505 | |
30 | Samsung Medical Center | Seoul | Korea, Republic of | 06351 | |
31 | Netherlands Cancer institute | Amsterdam | Netherlands | 1066 CX | |
32 | National Cancer Center Singapore | Singapore | Singapore | 169610 | |
33 | Hospital Universitari Vall d'Hebron | Barcelona | Spain | 08035 | |
34 | Hospital Universitario Fundación Jiménez Díaz- START MADRID | Madrid | Spain | 28040 | |
35 | Hospital Universitario HM Sanchinarro-START MADRID-CIOCC | Madrid | Spain | 28050 | |
36 | Clinica de Universidad de Navarra | Pamplona | Spain | 31008 | |
37 | Hospital Clínico Universitario de Valencia | Valencia | Spain | 46010 | |
38 | Karolinska University Hospital | Stockholm | Sweden | 17176 | |
39 | China Medical University Hospital | Taichung | Taiwan | 40447 | |
40 | Sarah Cannon Research Institute UK | London | United Kingdom | W1G 6AD | |
41 | The Christie NHS Foundation Trust | Manchester | United Kingdom | M20 4BX |
Sponsors and Collaborators
- Relay Therapeutics, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RLY-4008-101