RLY-4008-101 - A First-in-Human Study of Highly Selective FGFR2 Inhibitor, RLY-4008, in Patients With Intrahepatic Cholangiocarcinoma (ICC) and Other Advanced Solid Tumors

Studio Clinico

Patologia: Tumori delle vie biliari, Altre neoplasie

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: No

Fase di studio: 1, II

Linee di trattamento: Prima linea, Seconda linea

Criteri di inclusione: 

- 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

- 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.

Criteri di esclusione: 

- 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.

Trattamento sperimentale: 

RLY-4008

Trattamento di controllo: 

NA

Obiettivi primari dello studio: 

- Part 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 ]
- Part 1: Number of patients with adverse events and serious adverse events [ Time Frame: Every cycle (4-week cycles) until study discontinuation, approximately 24 months ]
- Part 2 and Part 3: Objective Response Rate (ORR) assessed by Independent Review Committee per 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 ].

Centri partecipanti

Nord Italia

Centro Italia

Informazioni Generali

Protocollo

Numero di iscrizione a registro: NCT04526106 - 2020-004535-24

Data di inserimento: 12.06.2023

Promotore

Relay Therapeutics, Inc

Principal Investigator ITALIA

Istituto Europeo di Oncologia

Riferimento: Prof. Giuseppe Curigliano

Telefono: 0257489599

Email: giuseppe.curigliano@ieo.it

Localita: Milano