Study of oral FGF401 in adult patients with liver cancer or other types of cancer

Phase 1

Conditions: 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: Hepatocellular carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-002929-35-ES

Lead Sponsor: ovartis Farmacéutica, S.A.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 130

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

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 < 75000/mm3
Absolute neutrophil count (ANC) < 1500/mm3
? Chemistry
Total bilirubin ? 2 mg/dL
AST and/or ALT > 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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> Main Objective: 1. Phase I part: to estimate the MTD and/or RP2D of FGF401<br> 2. Phase II part: to investigate the anti-tumor activity of FGF401<br> ;<br> Secondary Objective: 1. To characterize the safety and tolerability of FGF401<br> 2. To further investigate the anti-tumor activity of FGF401<br> 3. To characterize the PK properties of FGF401<br> ;<br> Primary end point(s): 1. Incidence rate and characteristics of DLT during the first cycle of dosing<br> 2. Group 1 and Group 2: Time to progression (TTP); Group 3: Overall response rate (ORR), based on local assessment per RECIST v1.1<br> ;<br> Timepoint(s) of evaluation of this end point: 1. First cycle<br> 2. Baseline and every 6 weeks<br>

Secondary Outcome Measures

Name	Time	Method

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