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

Sponsor
Relay Therapeutics, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04526106
Collaborator
(none)
440
41
3
49
10.7
0.2

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).

Study Design

Study Type:
Interventional
Anticipated Enrollment :
440 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Intervention 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 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 3: Non-CCA patients with an FGFR2 fusion Group 4: Non-CCA patients with an FGFR2 amplification Group 5: Non-CCA patients with an FGFR2 mutation Group 6: CCA patients with an FGFR2 fusion with no prior chemotherapy and not previously treated with an FGFRi Group 7: CCA patients with an FGFR2 mutation or amplification Part 3 (Extension of Part 2, Group 2): • CCA patients with an FGFR2 fusion with prior chemotherapy but not previously treated with an FGFRiPart 1 (multiple ascending doses):• Unresectable or metastatic CCA or other unresectable or metastatic solid tumorPart 2 (RP2D determined in Part 1):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 3: Non-CCA patients with an FGFR2 fusion Group 4: Non-CCA patients with an FGFR2 amplification Group 5: Non-CCA patients with an FGFR2 mutation Group 6: CCA patients with an FGFR2 fusion with no prior chemotherapy and not previously treated with an FGFRi Group 7: CCA patients with an FGFR2 mutation or amplificationPart 3 (Extension of Part 2, Group 2):• CCA patients with an FGFR2 fusion with prior chemotherapy but not previously treated with an FGFRi
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Sep 2, 2020
Anticipated Primary Completion Date :
Apr 1, 2024
Anticipated Study Completion Date :
Oct 1, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. 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]

  2. 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]

  3. Number of patients with adverse events and serious adverse events [Every cycle (4-week cycles) until study discontinuation, approximately 24 months]

Secondary Outcome Measures

  1. 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]

  2. 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]

  3. 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]

  4. 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)]

  5. 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)]

  6. 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)]

  7. 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]

  8. 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]

  9. 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

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No

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 (except for Group 6, as defined below)

  • 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. A single cycle of palliative chemotherapy is allowed during screening

  • Group 7: CCA patients with an FGFR2 mutation or amplification

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

  • Group 3: Non-CCA patients with an FGFR2 fusion

  • Group 4: Non-CCA patients with an FGFR2 amplification

  • Group 5: Non-CCA patients with an FGFR2 mutation

  • 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)

  • 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

Contacts and Locations

Locations

Site City State Country Postal Code
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.
Responsible Party:
Relay Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT04526106
Other Study ID Numbers:
  • RLY-4008-101
First Posted:
Aug 25, 2020
Last Update Posted:
Jul 11, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 11, 2022