FGF401 in HCC and Solid Tumors Characterized by Positive FGFR4 and KLB Expression

NCT02325739 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: CFGF401X21012014-002929-35
• Study Type: interventional
• Target: 172
• Locations: 11 countries
• Sites: 27

Brief Summary

Estimate the maximum tolerated dose and/or recommended phase II dose and efficacy of FGF401 as single agent and in combination with PDR001 in patients with hepatocellular carcinoma and as single agent in patients with other solid malignancies based on RECIST 1.1.

Conditions

Hepatocellular Carcinoma (HCC); Solid Malignancies

Keywords

FGF401; PDR001; PD-1; FGFR4; FGF19; HCC; solid malignancies characterized by positive FGFR4 and KLB expression

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only

  A dose-limiting toxicity was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the evaluation period of DLTs and met any of the criteria listed. The estimation of the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of the treatment was based upon the estimation of the probability of DLT during the evaluation period for subjects in the dose determining set (DDS). A subject with multiple occurrences of a DLT under one treatment is counted only once in the AE category for that treatment. A subject with multiple DLTs within a primary system organ class is counted only once in the total row.

  Cycle 1 (C1) (21 days) for FGF401 single agent, Cycle 1 and Cycle 2 (C2) (42 days) for FGF401 and PDR001 combination

• Time to Progression (TTP): Group 1 & Group 2 (Phase II Only)

  TTP is defined as the date of start treatment to the date of event defined as the first documented progression or death due to underlying cancer. Method used was Kaplan-Meier analysis. Group 1: HCC subjects form Asian countries; Group 2: HCC subjects form non-Asian countries

  approx. 4.5 years

• Overall Response Rate (ORR) Based on Local Assessment: Group 3 (Phase II Only)

  ORR is defined as the percentage of patients with a best overall response of CR or PR (RECIST v1.1). FGF401 single agent-Phase II part - Group 3 (non-HCC, other solid tumors).

  approx. 4.5 years

Secondary Outcomes (15)

• Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II

  approx. 4.5 years

• Overall Response Rate (ORR) by Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1 & 2

  approx. 4.5 years

• Disease Control Rate (DCR) by Local Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1, 2 & 3

  approx. 4.5 years

• Time to Progression (TTP) in Participants Dosed With Single Agent FGF401 120 mg (Fasted & Fed) & With Combination FGF401 120 mg + PDR001 300 mg Q3W (Phase I)

  approx. 4.5 years

• Overall Survival (OS) in Participants Dosed With Single Agent FGF401 120 mg (Fasted & Fed) and in Participants Dosed With Combination FGF401 120 mg and PDR001 300 mg Q3W (Phase I & II)

  start of treatment to death, up to about 53 months

Study Arms (11)

Phase I: FGF401 50 mg fasted

EXPERIMENTAL

Participants received single agent FGF401 50 mg while fasted

Drug: FGF401

Phase I: FGF401 80 mg fasted

EXPERIMENTAL

Participants received single agent FGF401 80 mg while fasted

Drug: FGF401

Phase I: FGF401 80 mg fed

EXPERIMENTAL

Participants received single agent FGF401 80 mg while fed

Drug: FGF401

Phase I: FGF401 120 mg fasted

EXPERIMENTAL

Participants received single agent FGF401 120 mg while fasted

Drug: FGF401

Phase I: FGF401 120 mg fed

EXPERIMENTAL

Participants received single agent FGF401 120 mg while fed

Drug: FGF401

Phase I: FGF401 150 mg fasted

EXPERIMENTAL

Participants received single agent FGF401 150 mg while fasted

Drug: FGF401

Phase I: FGF401 80 mg + PDR001 300 mg

EXPERIMENTAL

Participants received FGF401 80 mg in combination with PDR001 300 mg while fasted

Drug: FGF401; Biological: PDR001

Phase I: FGF401 120 mg + PDR001 300 mg

EXPERIMENTAL

Participants received FGF401 120 mg in combination with PDR001 300 mg while fasted

Drug: FGF401; Biological: PDR001

Phase II: Group 1 - FGF401 120 mg QD

EXPERIMENTAL

Group 1 was comprised of HCC participants from Asian countries who received single agent FGF401 120 mg QD while fasted

Drug: FGF401

Phase II: Group 2 - FGF401 120 mg QD

EXPERIMENTAL

Group 2 was comprised of HCC participants from non-Asian countries who took single agent FGF401 120 mg QD while fasted

Drug: FGF401

Phase II: Group 3 - FGF401 120 mg QD

EXPERIMENTAL

Group 3 was comprised of participants with other solid malignancies regardless of geography who took single agent FGF401 120 mg QD while fasted

Drug: FGF401

Interventions

FGF401 DRUG

FGF401 is a FGFR4 inhibitor.

Phase I: FGF401 120 mg + PDR001 300 mg; Phase I: FGF401 120 mg fasted; Phase I: FGF401 120 mg fed; Phase I: FGF401 150 mg fasted; Phase I: FGF401 50 mg fasted; Phase I: FGF401 80 mg + PDR001 300 mg; Phase I: FGF401 80 mg fasted; Phase I: FGF401 80 mg fed; Phase II: Group 1 - FGF401 120 mg QD; Phase II: Group 2 - FGF401 120 mg QD; Phase II: Group 3 - FGF401 120 mg QD

PDR001 BIOLOGICAL

PDR001 is a humanized anti-PD1 IgG4 antibody that blocks the binding of PD-L1 and PD-L2

Phase I: FGF401 120 mg + PDR001 300 mg; Phase I: FGF401 80 mg + PDR001 300 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ECOG Performance Status ≤ 1
• Presence of at least one measurable lesion according to RECIST v1.1. c-i) FGF401 single agent-Phase I and Phase II, Group 3: 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. c-ii) FGF401 single agent-Phase II, Groups 1 and 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 c-iii) FGF401 in combination with PDR001:Advanced HCC patients who have received up to 2 previous lines of systemic treatment and one treatment must have included sorafenib with documented disease progression during or after discontinuation of sorafenib treatment, or intolerance to sorafenib treatment

You may not qualify if:

• Previous treatment with a selective FGF19-FGFR4 targeted therapy and/or pan-FGFR inhibitor.
• Symptomatic CNS metastases which are neurologically unstable or requiring increasing doses of steroids to control their CNS disease.
• 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 more than ULN or INR \> 1.7
• Pregnant or nursing (lactating) women.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (27)

University of California LA Santa Monica Location

Los Angeles, California, 90095, United States

Location

Massachusetts General Hospital Oncology Dept

Boston, Massachusetts, 02114, United States

Location

Uni Of TX MD Anderson Cancer Cntr

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Shanghai, Shanghai Municipality, 200032, China

Location

Novartis Investigative Site

Rennes, Ille Et Vilaine, 35062, France

Location

Novartis Investigative Site

Lille, 59037, France

Location

Novartis Investigative Site

Montpellier, 34295, France

Location

Novartis Investigative Site

Pessac, 33604, France

Location

Novartis Investigative Site

Toulouse, 31059, France

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

Würzburg, 97080, Germany

Location

Novartis Investigative Site

Hong Kong, Hong Kong

Location

Novartis Investigative Site

Milan, MI, 20132, Italy

Location

Novartis Investigative Site

Modena, MO, 41124, Italy

Location

Novartis Investigative Site

Ōsaka-sayama, Osaka, 589 8511, Japan

Location

Novartis Investigative Site

Chuo Ku, Tokyo, 104 0045, Japan

Location

Novartis Investigative Site

Singapore, 168583, Singapore

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Seoul, 05505, South Korea

Location

Novartis Investigative Site

Seoul, 06351, South Korea

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

Location

Novartis Investigative Site

Madrid, 28034, Spain

Location

Novartis Investigative Site

Tainan, 70403, Taiwan

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Related Publications (2)

• Chan SL, Schuler M, Kang YK, Yen CJ, Edeline J, Choo SP, Lin CC, Okusaka T, Weiss KH, Macarulla T, Cattan S, Blanc JF, Lee KH, Maur M, Pant S, Kudo M, Assenat E, Zhu AX, Yau T, Lim HY, Bruix J, Geier A, Guillen-Ponce C, Fasolo A, Finn RS, Fan J, Vogel A, Qin S, Riester M, Katsanou V, Chaudhari M, Kakizume T, Gu Y, Porta DG, Myers A, Delord JP. A first-in-human phase 1/2 study of FGF401 and combination of FGF401 with spartalizumab in patients with hepatocellular carcinoma or biomarker-selected solid tumors. J Exp Clin Cancer Res. 2022 Jun 2;41(1):189. doi: 10.1186/s13046-022-02383-5.

  PMID: 35655320 DERIVED

• Castanon Alvarez E, Giallombardo M, Gil-Bazo I, Papadimitriou K, Pauwels P, Peeters M, Rolfo C. Looking into the "Garden of the Hesperides": new drugs for hepatocellular carcinoma. Minerva Chir. 2015 Apr;70(2):119-29. Epub 2015 Jan 23.

  PMID: 25614940 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

roblitinib; spartalizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2014
• First Posted: December 25, 2014
• Study Start: December 29, 2014
• Primary Completion: May 30, 2019
• Study Completion: May 30, 2019
• Last Updated: October 21, 2024
• Results First Posted: December 17, 2020

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share

Locations

IT (2); FR (5); DE (4); JP (2); HK (1); CN (1); KR (3); ES (3); SG (1); US (3); TW (2)