FGFR2 Gene Fusion/Rearrangement, Other Solid Tumors, Adult
Conditions
Brief summary
The goal of this clinical trial is to evaluate if lirafugratinib is efficacious and safe to treat adult patients with previously treated, unresectable, locally advanced or metastatic solid tumors (excluding cholangiocarcinoma) harboring FGFR2 fusion or rearrangement. Participants will: * Take lirafugratinib regularly as instructed by their study doctor. * Visit the clinic as instructed for checkups and tests. * Keep a diary recording each time a dose of lirafugratinib is taken.
Interventions
DRUGLirafugratinib
Lirafugratinib is an oral inhibitor of FGFR2
Sponsors
Elevar Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Unresectable, locally advanced, or metastatic solid tumor (other than CCA). * Documented FGFR2 gene fusion or rearrangement 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. * Previously (\>30 days) treated with ≥1 line of systemic therapy including chemotherapy (e.g., gemcitabine/cisplatin), immunotherapy, radiation therapy, or other approved therapies. * Subject has not received prior treatment with an FGFRi.
Exclusion criteria
* An uncontrolled comorbidity. * 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR) assessed by Independent Review Committee 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation between FGFR2 genotype by central tissue assessment and antitumor response, as measured by Objective Response Rate (ORR). | Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months. | — |
| 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. | — |
| 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. | — |
| 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 | — |
| Change from baseline in quality of life as assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). | Approximately every 4 weeks during treatment, approximately 24 months | It scores (0-100) where higher means better function/quality of life in that section of the questionnaire and higher means worse symptoms in that section of the questionnaire. |
| Duration of response (DOR) assessed by Independent Review Committee 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. | — |
| Number of patients with adverse events and serious adverse events. | Every cycle (4-week cycles) until study discontinuation, approximately 24 months. | — |
| Number of patients with dose interruptions. | Every 28-day cycle until end of treatment, approximately 24 months. | — |
| Number of patients with dose reductions. | Every 28-day cycle until end of treatment, approximately 24 months. | — |
| Number of patients with dose discontinuations. | Every 28-day cycle until end of treatment, approximately 24 months. | — |
| Objective Response Rate (ORR) as assessed by Investigator 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. | — |
| Duration of Response (DOR) as assessed by Investigator 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 | — |
| Disease control rate (DCR) as assessed by Investigator and Independent Review Committee 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. | — |
| Progression-free survival (PFS) as assessed by Investigator and Independent Review Committee 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 | — |
| Overall survival (OS). | Up to approximately 36 months. | — |
| Time to response (TTR) assessed by Investigator and Independent Review Committee per RECIST v1.1. | Up to approximately 36 months. | — |
| Time to progression (TTP) assessed by Investigator and Independent Review Committee per RECIST v1.1. | Up to approximately 36 months | — |
| Pharmacokinetic parameters including maximum plasma drug concentration (Cmax) | [Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through Cycle 4 (4-week cycles)] | — |
| Pharmacokinetic parameters including area under the plasma concentration versus time curve (AUC) | Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through Cycle 4 (4-week cycles) | — |
| Pharmacokinetic parameters including half-life (t1/2) | Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through Cycle 4 (4-week cycles) | — |
| 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 | — |
| Time to deterioration (TTD). | Up to approximately 36 months. | — |
Countries
France, South Korea, Spain, United Kingdom, United States
Contacts
CONTACTElevar Therapeutics
Outcome results
None listed