A First-in-Human Study of Highly Selective FGFR2 Inhibitor, RLY-4008, in Patients With Intrahepatic Cholangiocarcinoma (ICC) and Other Advanced Solid Tumors
Study Identifier:
RLY-4008-101
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
N/A
Study Complete
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Study Summary
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 unresectable or metastatic ICC and other unresectable or metastatic solid tumors. Adverse events (AEs), PK, ctDNA and anti-tumor activity (RECIST 1.1) were assessed. To assess the utility of a de novo FGFR2 f/r calling algorithm in identifying these alterations. To evaluate the feasibility (failure rate) and the sensitivity (percent positive agreement [PPA]) of the novel cfDNA f/r-calling algorithm to compare to the local and central tissue assessments for identifying FGFR2 f/r. To report initial efficacy and safety from pts with solid tumors other than CCA treated at the RP2D. Key objectives were investigator-assessed objective response rate (ORR), duration of response (DOR), and safety. Efficacy was analyzed in pts with measurable disease, no prior FGFRi therapy and an opportunity for ³1 post-baseline imaging assessment. Safety was analyzed in all pts.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
I/II
Sex
Female & Male
Age
18+ years
Study Drug
Study Status
Indicates the current recruitment status or the expanded access status
Study Complete
Requirements information
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 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. Note: For Group 7, patients with confirmed diagnosis of unresectable or metastatic CCA with an FGFR2 fusion are not eligible. 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
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). 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
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Barcelona
Barcelona, Spain, 08023
Investigator
Tatiana Hernandez Guerrero
Status
Recruiting
Condition(s) Treated at Site
Gene Mutations
Bile Duct
Solid Tumor