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

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ClinicalTrials.gov Identifier: NCT04526106
Recruitment Status : Recruiting
First Posted : August 25, 2020
Last Update Posted : May 5, 2022
Sponsor:
Information provided by (Responsible Party):
Relay Therapeutics, Inc.

Brief Summary:
This is an open-label, FIH study designed to evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary antineoplastic activity of RLY-4008, a potent and highly selective fibroblast growth factor receptor 2 (FGFR2) inhibitor administered orally patients with unresectable or metastatic ICC and other unresectable or metastatic solid tumors. This study consists of 2 parts, a dose escalation (Part 1) and a dose expansion (Part 2).

Condition or disease Intervention/treatment Phase
FGFR2 Amplification FGFR2 Gene Mutation FGFR2 Gene Rearrangement FGFR2 Gene Translocation FGFR2 Gene Activation Intrahepatic Cholangiocarcinoma Cholangiocarcinoma Other Solid Tumors, Adult Drug: RLY-4008 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Part 1 (multiple ascending doses):

• unresectable or metastatic ICC or other unresectable or metastatic solid tumor

Part 2 (RP2D determined in Part 1):

  • Group 1: ICC with a FGFR2 fusion previously treated with a pan-FGFR inhibitor
  • Group 2: ICC with a FGFR2 fusion not previously treated with a pan-FGFR inhibitor
  • Group 3: patients with an FGFR2 fusion and solid tumor other than ICC
  • Group 4: unresectable or metastatic solid tumor patients with FGFR2 amplification
  • Group 5: unresectable or metastatic solid tumor patients with an oncogenic FGFR2 mutation
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 : September 2, 2020
Estimated Primary Completion Date : April 2024
Estimated Study Completion Date : October 2024


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




Primary Outcome Measures :
  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 ]
  2. Number of patients with adverse events and serious adverse events [ Time Frame: Every cycle (4-week cycles) until study discontinuation, approximately 24 months ]

Secondary Outcome Measures :
  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 ]
  2. Overall response rate (ORR) as assessed by 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 ]
  3. Duration of Response (DOR) as assessed by 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 ]
  4. Disease Control Rate (DCR) as assessed by 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 ]
  5. Pharmacokinetic parameters including maximum plasma drug concentration (Cmax) [ Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle though Cycle 4 (4-week cycles) ]
  6. Pharmacokinetic parameters including area under the plasma concentration versus time curve from time 0 to 24 hours postdose (AUC0-24) [ Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle though Cycle 4 (4-week cycles) ]
  7. Pharmacokinetic parameters including terminal elimination half-life (t1/2) [ Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle though Cycle 4 (4-week cycles) ]
  8. 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 ]
  9. 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 ]
  10. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • Additional FGFR2 alterations/tumor types may be considered for the Part 1 dose escalation
  • Part 2 dose expansion patients must additionally meet the group requirements detailed below.

    • Group 1: patient must have a confirmed diagnosis of unresectable or metastatic ICC with FGFR2 fusion (per local assessment of blood and/or tumor) and has received prior treatment with a pan-FGFR inhibitor (eg, pemigatinib, erdafitinib, infigratinib, futibatinib).
    • Group 2: patient must have a confirmed diagnosis of unresectable or metastatic ICC with FGFR2 fusion (per local assessment of blood and/or tumor) and has NOT received prior treatment with a pan-FGFR inhibitor (eg, pemigatinib, erdafitinib, infigratinib, futibatinib).
    • Group 3: patient has an unresectable or metastatic solid tumor with FGFR2 fusion (per local assessment of blood and/or tumor) other than ICC.
    • Group 4: patient has an unresectable or metastatic solid tumor with FGFR2 amplification (per local assessment of blood and/or tumor).
    • Group 5: patient has an unresectable or metastatic solid tumor with an oncogenic FGFR2 mutation (per local assessment of blood and/or tumor).
  • 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
  • Patient must have measurable or evaluable disease per RECIST v1.1
  • Patient has ECOG performance status of 0-1

Key Exclusion Criteria

  • Ongoing, clinically significant FGFR inhibitor-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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04526106


Contacts
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Contact: Relay Therapeutics, Inc. 617-322-0731 ClinicalTrials@relaytx.com

Locations
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Sponsors and Collaborators
Relay Therapeutics, Inc.
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Responsible Party: Relay Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04526106    
Other Study ID Numbers: RLY-4008-101
First Posted: August 25, 2020    Key Record Dates
Last Update Posted: May 5, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Cholangiocarcinoma
Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type