Hepatocellular carcinoma or other solid tumors characterized by positive FGFR4 and KLB expression MedDRA version: 17.0 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 17.0 Level: PT Classification code 10073071 Term: Hepatocellu
Conditions
Interventions
Product Code: FGF401
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: FGF401
CAS Number: FGF401
Current Sponsor code: FGF401
Sponsors
Novartis Farmacéutica, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients (male or female) ? 18 years of age 2. ECOG Performance Status ? 1 3. Presence of at least one measurable lesion according to RECIST v1.1. 4. Patients with confirmed positive expression of FGFR4 and KLB at pre-screening. 5. For HCC patients: the diagnosis must be made based on AASLD Guidelines with confirmed stage C advanced HCC (BCLC staging classification). Current cirrhotic status of Child-Pugh class A (5-6 points), with no encephalopathy and/or ascites. 6. Phase I: Patients with HCC or advanced solid tumors, who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists. 7. Phase 2: HCC patients previously treated with sorafenib for advanced HCC with documented disease progression during or after discontinuation of sorafenib treatment, or intolerance to sorafenib treatment. Other protocol-defined inclusion criteria may apply. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 65 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 65
Exclusion criteria
Exclusion criteria: 1. Previous treatment with a FGF19-FGFR4 targeting therapy. 2. For HCC patients in Phase II part: any previous systemic anti-cancer therapies other than sorafenib or any anti-cancer therapy (including locoregional therapy) after disease progression during or after sorafenib treatment. 3. Ongoing active diarrhea requiring medications (e.g. BAS, loperamide) 4. Irritable bowel syndrome with signs/symptoms and requires medications 5. Symptomatic CNS metastases which are neurologically unstable or requiring increasing doses of steroids to control their CNS disease. 6. Patient having out of range laboratory values defined as: ? Hematology Hemoglobin ? 9 g/dL (SI Units: 90 g/L) Platelet count 3 x ULN Serum creatinine > 1.5 x ULN and/or creatinine clearance ? 45 mL/min ? Coagulation: PT ? 4 seconds or INR ? 1.7 7. Unable to stop any prohibited medications, including CYP1A2, CYP2C9 and CYP3A substrates with a narrow therapeutic index, long acting proton pump inhibitors, and strong BSEP efflux transporter inhibitors. Other protocol-defined exclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. Phase I part: to estimate the MTD and/or RP2D of FGF401 2. Phase II part: to investigate the anti-tumor activity of FGF401 ; Secondary Objective: 1. To characterize the safety and tolerability of FGF401 2. To further investigate the anti-tumor activity of FGF401 3. To characterize the PK properties of FGF401 ; Primary end point(s): 1. Incidence rate and characteristics of DLT during the first cycle of dosing 2. Group 1 and Group 2: Time to progression (TTP); Group 3: Overall response rate (ORR), based on local assessment per RECIST v1.1 ; Timepoint(s) of evaluation of this end point: 1. First cycle 2. Baseline and every 6 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Safety: Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs and ECGs Tolerability: Dose interruptions and reductions 2. Phase I part: BOR, ORR, DCR, TTP and OS, based on local assessment per RECIST v1.1 Phase II part: ? Group 1 and Group 2: BOR, ORR, OS and DCR, based on local assessment per RECIST v1.1 ? Group 3: BOR, DCR, OS and PFS, based on local assessment per RECIST v1.1 3. Plasma concentration of FGF401 and PK parameters including but not limited to Cmax, Cmin, AUCinf, AUClast, AUCtau and T1/2 ; Timepoint(s) of evaluation of this end point: 1. Continuously throughout the study until 30 days after safety follow up 2. Baseline and every 6 weeks 3. During phase I: Cycle 1 Day 1, 2, 8, 9 and 15; Cycle 2 Day 1 and 2; Cycle 3 and Cycle 4 Day 1 During Phase II: Cycle 1 Day 1, 2, 8 and 15; Cycle 2 Day 1 and 2; Cycle 3 to Cycle 6 Day 1 | — |
Countries
China, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Singapore, Spain, Taiwan, United States
Contacts
Public ContactDepartamento Médico Oncología (GMO)
Novartis Farmacéutica, S.A.
Outcome results
None listed