Clinical Trials /

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

NCT04526106

Description:

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 in patients with intrahepatic cholangiocarcinoma (ICC) and other advanced solid tumors. This study consists of 2 parts, a dose escalation (Part 1) and a dose expansion (Part 2).

Related Conditions:
  • Intrahepatic Cholangiocarcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: First-in-human Study of Highly Selective FGFR2 Inhibitor, RLY-4008, in Patients With ICC and Other Advanced Solid Tumors
  • 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

Clinical Trial IDs

  • ORG STUDY ID: RLY-4008-101
  • NCT ID: NCT04526106

Conditions

  • Solid Tumor, Adult
  • FGFR2 Amplification
  • FGFR2 Gene Mutation
  • FGFR2 Gene Rearrangement
  • FGFR2 Gene Translocation
  • FGFR2 Gene Activation
  • Intrahepatic Cholangiocarcinoma
  • Cholangiocarcinoma
  • Endometrial Cancer
  • Gastric Cancer
  • Breast Cancer

Interventions

DrugSynonymsArms
RLY-4008Part 1: Dose Escalation

Purpose

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 in patients with intrahepatic cholangiocarcinoma (ICC) and other advanced solid tumors. This study consists of 2 parts, a dose escalation (Part 1) and a dose expansion (Part 2).

Trial Arms

NameTypeDescriptionInterventions
Part 1: Dose EscalationExperimentalMultiple doses of RLY-4008 for oral administration.
  • RLY-4008
Part 2: Dose ExpansionExperimentalOral dose of RLY-4008 as determined during Part 1 Dose Escalation.
  • RLY-4008

Eligibility Criteria

        Key Inclusion Criteria

          -  Histologically or cytologically confirmed unresectable, advanced 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 - Patients must have unresectable, intrahepatic cholangiocarcinoma with
                  FGFR2 fusion previously treated with a pan-FGFR inhibitor

               -  Group 2 - Patients must have unresectable, intrahepatic cholangiocarcinoma with
                  FGFR2 fusion NOT previously treated with a pan-FGFR inhibitor

               -  Group 3 - Patients must have advanced, unresectable solid tumor with FGFR2 fusion
                  other than ICC

               -  Group 4 - Patients must have, advanced, unresectable solid tumor with FGFR2
                  amplification

               -  Group 5 - Patients must have advanced, unresectable solid tumor with an oncogenic
                  FGFR2 mutation

          -  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 0-2

        Key Exclusion Criteria

          -  Ongoing, clinically significant corneal or retinal disorder

          -  Patient has any of the following within 14 days prior to the first dose of RLY-4008:

               -  Platelet count < 75 x 10^9 /L

               -  Absolute neutrophil count (ANC) < 1 x 10^9 /L

               -  Hemoglobin < 8 g/dL (red blood cell transfusion and erythropoietin may be used to
                  reach 8 g/dL, but must have been administered at least 2 weeks prior to the first
                  dose of RLY-4008)

               -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x the
                  upper limit of normal (ULN) if no hepatic metastases are present; > 5 x ULN if
                  hepatic metastases are present

               -  Total bilirubin > 1.5 x ULN; > 3 x ULN with direct bilirubin > 1.5 x ULN in
                  presence of Gilbert's disease

               -  Estimated (Cockcroft-Gault formula) or measured creatinine clearance < 50 mL/min

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Relay Therapeutics, Inc.

Last Updated

August 20, 2020