Hepatocellular Carcinoma (HCC)Phase 1/2NCT02325739
FGF401 in HCC and Solid Tumors Characterized by Positive FGFR4 and KLB Expression
A Phase 1/2 study testing FGF401 and PDR001 in people with Hepatocellular Carcinoma (HCC) and Solid Malignancies, run by Novartis Pharmaceuticals at 27 sites in 11 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma (HCC), Solid Malignancies
- What is being tested?
- FGF401 and PDR001
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 172 participants
- Where
- 27 sitesin 11 countries
- Study dates
- 29 Dec 2014to 30 May 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
- Other protocol-defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
27 sites in 11 countries.
27 sites in 11 countries
France5 sites
Novartis Investigative Site
Lille, 59037
Novartis Investigative Site
Montpellier, 34295
Novartis Investigative Site
Pessac, 33604
Novartis Investigative Site
Rennes, Ille Et Vilaine, 35062
Novartis Investigative Site
Toulouse, 31059
Germany4 sites
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Hanover, 30625
Novartis Investigative Site
Heidelberg, 69120
Novartis Investigative Site
Würzburg, 97080
United States3 sites
Massachusetts General Hospital Oncology Dept
Boston, Massachusetts, 02114
Uni Of TX MD Anderson Cancer Cntr
Houston, Texas, 77030
University of California LA Santa Monica Location
Los Angeles, California, 90095
South Korea3 sites
Novartis Investigative Site
Seoul, 03080
Novartis Investigative Site
Seoul, 05505
Novartis Investigative Site
Seoul, 06351
Spain3 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Barcelona, Catalonia, 08036
Novartis Investigative Site
Madrid, 28034
Italy2 sites
Novartis Investigative Site
Milan, MI, 20132
Novartis Investigative Site
Modena, MO, 41124
Japan2 sites
Novartis Investigative Site
Chuo Ku, Tokyo, 104 0045
Novartis Investigative Site
Ōsaka-sayama, Osaka, 589 8511
Taiwan2 sites
Novartis Investigative Site
Tainan, 70403
Novartis Investigative Site
Taipei, 10002
About this study
Official title: A Phase I/II, Multicenter, Open-label Study of Oral FGF401 in Adult Patients With Hepatocellular Carcinoma or Solid Malignancies Characterized by Positive FGFR4 and KLB Expression
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.
Read the detailed description
The primary objectives of this study were in 2 parts: Phase l \& Phase II.
The study included different periods starting by molecular pre-screening (applicable for all subjects enrolled under protocol versions 00 to 03, or applicable only for Phase I and Group 3 in Phase II of FGF401 single agent, for subjects enrolled under protocol version 04), Screening, Treatment, End of Treatment, Disease progression follow-up (if applicable), Safety follow-up and then ended by survival follow-up period
In the Phase I part, subjects with HCC or other advanced solid tumors characterized by positive FGFR4 and KLB expression were enrolled and treated with FGF401 as a single agent or in combination with PDR001. Subjects in this phase were dosed under fasted or fed conditions.
In the Phase 2 part, subjects with advanced HCC or other solid tumors bearing positive FGFR4 and KLB expression were enrolled into three groups (Group 1: HCC subjects from Asian countries; Group 2: HCC subjects from non-Asian countries; Group 3: Subjects with other solid malignancies regardless of geography) to assess the preliminary anti-tumor activity of FGF401 in Phase ll. This Phase II part investigated the anti-tumor activity of FGF401 single agent and in combination with PDR001.
Each group within the Phase II dose expansion part targeted a different number of subjects. Group 1 and Group 2 planned to enroll around 40 subjects each and Group 3 planned to enroll approximately 20 subjects. Subjects in this phase were dosed under fasted conditions.
Oral FGF401 was administered on a continuous once daily (QD) dosing regimen for both FGF401 single agent and in combination with PDR001 parts. Intravenous PDR001 was administered in a fixed dosing regimen of 300 mg iv every three weeks as per protocol until subject experienced unacceptable toxicity, progressive disease and/or treatment was discontinued at the discretion of the Investigator or withdrawal of consent.
Because the enrollment of new subjects in this study was halted for business reason on 03-Jul-2018 early enrollment termination was declared following the initial halt of enrollment once the global last subject last visit was achieved as per protocol, and consequently the phase II part of the FGF401+PDR001 combination did not start, none of the planned analyses related to the phase II part of the FGF401+PDR001 combination arm were performed.
Duration of treatment: Subjects could continue study treatment until they experienced any of the following: Disease progression (radiologically documented according to RECIST v1.1) as assessed by the Investigator, unacceptable toxicity, \& treatment was discontinued at the discretion of the Investigator or the subject.
Subjects who permanently discontinued the study treatment for any reason other than disease progression or withdrawal of consent had to continue efficacy assessments as scheduled in the protocol until the time of disease progression.
- Conditions
- Hepatocellular Carcinoma (HCC), Solid Malignancies
- Being tested
- FGF401, PDR001
- Keywords
- FGF401, PDR001, PD-1, FGFR4, FGF19, HCC, solid malignancies characterized by positive FGFR4 and KLB expression
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FGF401Drug
FGF401 is a FGFR4 inhibitor.
PDR001Biological
PDR001 is a humanized anti-PD1 IgG4 antibody that blocks the binding of PD-L1 and PD-L2
| Study group | Role | What they receive |
|---|---|---|
| Phase I: FGF401 50 mg fasted | Experimental | Participants received single agent FGF401 50 mg while fasted Receives: Drug: FGF401 |
| Phase I: FGF401 80 mg fasted | Experimental | Participants received single agent FGF401 80 mg while fasted Receives: Drug: FGF401 |
| Phase I: FGF401 80 mg fed | Experimental | Participants received single agent FGF401 80 mg while fed Receives: Drug: FGF401 |
| Phase I: FGF401 120 mg fasted | Experimental | Participants received single agent FGF401 120 mg while fasted Receives: Drug: FGF401 |
| Phase I: FGF401 120 mg fed | Experimental | Participants received single agent FGF401 120 mg while fed Receives: Drug: FGF401 |
| Phase I: FGF401 150 mg fasted | Experimental | Participants received single agent FGF401 150 mg while fasted Receives: Drug: FGF401 |
| Phase I: FGF401 80 mg + PDR001 300 mg | Experimental | Participants received FGF401 80 mg in combination with PDR001 300 mg while fasted Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: FGF401 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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).
Measured: approx. 4.5 years
Secondary outcomes (15)
Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II
BOR is the best response recorded from the start of the treatment until disease progression/recurrence. BOR is determined according to: complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) and unknown.
Measured: approx. 4.5 years
Overall Response Rate (ORR) by Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1 & 2
ORR is defined as the proportion of patients with a best overall response of CR or PR (RECIST v1.1).
Phase I part and FGF401 single agent Phase II Group 1 (HCC, Asians) and Group 2 (HCC, non-Asians)
Measured: approx. 4.5 years
Disease Control Rate (DCR) by Local Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1, 2 & 3
DCR is the percentage of participants with a best overall response of CR or PR or SD per local assessment according to RECIST v1.1. Phase I part and FGF401 single agent Phase II Group 1 (HCC, Asians) and Group 2 (HCC, non-Asians) and Group 3 (non-HCC, other solid tumors).
Measured: 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)
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.
Measured: 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)
Overall survival (OS) is defined as the time from date of start of treatment to date of death due to any cause. If a patient was not known to have died, survival was censored at the date of last known date patient alive. Method used was Kaplan-Meier analysis.
Measured: start of treatment to death, up to about 53 months
Progression-free Survival (PFS) - FGF401 Single Agent Phase II: Group 3
Progression-free survival (PFS) is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. Group 3 - non-HCC, other solid tumors. Method used was Kaplan-Meier analysis.
Measured: 4.5 years
Presence and/or Concentration of Anti-PDR001 Antibodies
Serum PDR001 concentrations as well as immunogenicity analysis were performed for all subjects receiving PDR001. Treatment-induced ADA-positive percentage was based on percentage subjects ADA-negative at baseline. Treatment-boosted ADA-positive percentage was based on subjects ADA-positive at baseline.
Measured: Day 1 of Cycle 1 to 6, approx. 10 months after C1D1 and 150-day safety follow up (FU)
Cmax of PDR001 in Combination With FGF401: Phase I
Cmax is the maximum (peak) observed plasma drug concentration (mass x volume-1)
Measured: After the first dosing sample collection was at: C1D1 0hr , C1D1 1hr, C1D8 168hr, C1D15 336hr, C2D1 504hr; each cycle is 21 days
AUClast and AUCtau of PDR001 in Combination of FGF401: Phase I
AUClast: The AUC from time zero to the last measurable concentration sampling time (Tlast) (mass x time x volume-1)
AUCtau (AUC0 504h): The AUC calculated to the end of a dosing interval (tau) (amount x time x volume-1)
Measured: After the first dosing sample collection was at: C1D1 0hr , C1D1 1hr, C1D8 168hr, C1D15 336hr, C2D1 504hr; each cycle is 21 days
T1/2 of PDR001: Phase I
Due to the sparse PK sampling designed from PDR001, the PDR001 concentration data was insufficient for accurate estimation of secondary PK parameters including T1/2.
Measured: After the first dosing sample collection was at: C1D1 0hr , C1D1 1hr, C1D8 168hr, C1D15 336hr, C2D1 504hr; each cycle is 21 days
Cmax of FGF401: Phase I
Cmax is the maximum (peak) observed plasma drug concentration (mass x volume-1)
Measured: C1D1 (0 hour (h), 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h), C1D8 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h), and C2D1 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h)
Cmax of FGF401 in Combination With PDR001: Phase I
Cmax is the maximum (peak) observed plasma drug concentration (mass x volume-1)
Measured: C1D1 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h)
AUCinf, AUClast & AUCtau of FGF401: Phase I
AUCinf: The AUC from time zero to infinity (mass x time x volume-1)
AUClast: The AUC from time zero to the last measurable concentration sampling time (Tlast) (mass x time x volume-1)
AUCtau: The AUC calculated to the end of a dosing interval (tau) (amount x time x volume-1)
Measured: C1D1 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h), C1D8 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h), and C2D1 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h)
AUCinf, AUClast & AUCtau of FGF401 in Combination With PDR001: Phase I
AUCinf: The AUC from time zero to infinity (mass x time x volume-1)
AUClast: The AUC from time zero to the last measurable concentration sampling time (Tlast) (mass x time x volume-1)
AUCtau: The AUC calculated to the end of a dosing interval (tau) (amount x time x volume-1)
Measured: C1D1 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h)
T1/2 of FGF401: Phase I
The elimination half-life associated with the terminal slope ( z) of a semi logarithmic concentration-time curve (time).
Measured: C1D1 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h), C1D8 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h), and C2D1 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Dec 2014 (estimated)
- Study start29 Dec 2014
- Primary completion30 May 2019
- Study completion30 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular Carcinoma (HCC)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 172 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02325739
- Sponsor's protocol ID
- CFGF401X2101
- Other IDs
- 2014-002929-35, 2014
- Status last verified
- Sep 2024
- First submitted
- 9 Dec 2014
- Last updated
- 21 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Publications
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.
PubMed 35655320Castanon 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.
PubMed 25614940
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Multicenter, Open-label Study of Oral FGF401 in Adult Patients With Hepatocellular Carcinoma or Solid Malignancies Characterized by Positive FGFR4 and KLB Expression
- ClinicalTrials.gov ID
- NCT02325739
- Acronym / sponsor ID
- CFGF401X2101
- Conditions
- Hepatocellular Carcinoma (HCC), Solid Malignancies
- Keywords
- FGF401, PDR001, PD-1, FGFR4, FGF19, HCC, solid malignancies characterized by positive FGFR4 and KLB expression
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 172 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 29 Dec 2014 (actual)
- Primary completion
- 30 May 2019 (actual)
- Study completion
- 30 May 2019 (actual)
- First posted
- 25 Dec 2014 (estimated)
- Results
- Posted 17 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The primary objectives of this study were in 2 parts: Phase l \& Phase II.
The study included different periods starting by molecular pre-screening (applicable for all subjects enrolled under protocol versions 00 to 03, or applicable only for Phase I and Group 3 in Phase II of FGF401 single agent, for subjects enrolled under protocol version 04), Screening, Treatment, End of Treatment, Disease progression follow-up (if applicable), Safety follow-up and then ended by survival follow-up period
In the Phase I part, subjects with HCC or other advanced solid tumors characterized by positive FGFR4 and KLB expression were enrolled and treated with FGF401 as a single agent or in combination with PDR001. Subjects in this phase were dosed under fasted or fed conditions.
In the Phase 2 part, subjects with advanced HCC or other solid tumors bearing positive FGFR4 and KLB expression were enrolled into three groups (Group 1: HCC subjects from Asian countries; Group 2: HCC subjects from non-Asian countries; Group 3: Subjects with other solid malignancies regardless of geography) to assess the preliminary anti-tumor activity of FGF401 in Phase ll. This Phase II part investigated the anti-tumor activity of FGF401 single agent and in combination with PDR001.
Each group within the Phase II dose expansion part targeted a different number of subjects. Group 1 and Group 2 planned to enroll around 40 subjects each and Group 3 planned to enroll approximately 20 subjects. Subjects in this phase were dosed under fasted conditions.
Oral FGF401 was administered on a continuous once daily (QD) dosing regimen for both FGF401 single agent and in combination with PDR001 parts. Intravenous PDR001 was administered in a fixed dosing regimen of 300 mg iv every three weeks as per protocol until subject experienced unacceptable toxicity, progressive disease and/or treatment was discontinued at the discretion of the Investigator or withdrawal of consent.
Because the enrollment of new subjects in this study was halted for business reason on 03-Jul-2018 early enrollment termination was declared following the initial halt of enrollment once the global last subject last visit was achieved as per protocol, and consequently the phase II part of the FGF401+PDR001 combination did not start, none of the planned analyses related to the phase II part of the FGF401+PDR001 combination arm were performed.
Duration of treatment: Subjects could continue study treatment until they experienced any of the following: Disease progression (radiologically documented according to RECIST v1.1) as assessed by the Investigator, unacceptable toxicity, \& treatment was discontinued at the discretion of the Investigator or the subject.
Subjects who permanently discontinued the study treatment for any reason other than disease progression or withdrawal of consent had to continue efficacy assessments as scheduled in the protocol until the time of disease progression.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 11
| Arm | Type | Receives |
|---|---|---|
| Phase I: FGF401 50 mg fasted | Experimental | Drug: FGF401Participants received single agent FGF401 50 mg while fasted |
| Phase I: FGF401 80 mg fasted | Experimental | Drug: FGF401Participants received single agent FGF401 80 mg while fasted |
| Phase I: FGF401 80 mg fed | Experimental | Drug: FGF401Participants received single agent FGF401 80 mg while fed |
| Phase I: FGF401 120 mg fasted | Experimental | Drug: FGF401Participants received single agent FGF401 120 mg while fasted |
| Phase I: FGF401 120 mg fed | Experimental | Drug: FGF401Participants received single agent FGF401 120 mg while fed |
| Phase I: FGF401 150 mg fasted | Experimental | Drug: FGF401Participants received single agent FGF401 150 mg while fasted |
| Phase I: FGF401 80 mg + PDR001 300 mg | Experimental | Drug: FGF401, Biological: PDR001Participants received FGF401 80 mg in combination with PDR001 300 mg while fasted |
| Phase I: FGF401 120 mg + PDR001 300 mg | Experimental | Drug: FGF401, Biological: PDR001Participants received FGF401 120 mg in combination with PDR001 300 mg while fasted |
| Phase II: Group 1 - FGF401 120 mg QD | Experimental | Drug: FGF401Group 1 was comprised of HCC participants from Asian countries who received single agent FGF401 120 mg QD while fasted |
| Phase II: Group 2 - FGF401 120 mg QD | Experimental | Drug: FGF401Group 2 was comprised of HCC participants from non-Asian countries who took single agent FGF401 120 mg QD while fasted |
| Phase II: Group 3 - FGF401 120 mg QD | Experimental | Drug: FGF401Group 3 was comprised of participants with other solid malignancies regardless of geography who took single agent FGF401 120 mg QD while fasted |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (8 listed)
- 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:
- Pregnant or nursing (lactating) women.
- Other protocol-defined Inclusion/Exclusion criteria may apply.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FGF401FGF401 is a FGFR4 inhibitor. | Drug | 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 |
| PDR001PDR001 is a humanized anti-PD1 IgG4 antibody that blocks the binding of PD-L1 and PD-L2 | Biological | Phase I: FGF401 120 mg + PDR001 300 mg, Phase I: FGF401 80 mg + PDR001 300 mg |
Primary outcome
Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only
Time frame: Cycle 1 (C1) (21 days) for FGF401 single agent, Cycle 1 and Cycle 2 (C2) (42 days) for FGF401 and PDR001 combination
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.
Time to Progression (TTP): Group 1 & Group 2 (Phase II Only)
Time frame: approx. 4.5 years
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
Overall Response Rate (ORR) Based on Local Assessment: Group 3 (Phase II Only)
Time frame: approx. 4.5 years
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).
15 secondary outcomes
Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II
Time frame: approx. 4.5 years
Overall Response Rate (ORR) by Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1 & 2
Time frame: approx. 4.5 years
Disease Control Rate (DCR) by Local Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1, 2 & 3
Time frame: 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)
Time frame: 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)
Time frame: start of treatment to death, up to about 53 months
Progression-free Survival (PFS) - FGF401 Single Agent Phase II: Group 3
Time frame: 4.5 years
Presence and/or Concentration of Anti-PDR001 Antibodies
Time frame: Day 1 of Cycle 1 to 6, approx. 10 months after C1D1 and 150-day safety follow up (FU)
Cmax of PDR001 in Combination With FGF401: Phase I
Time frame: After the first dosing sample collection was at: C1D1 0hr , C1D1 1hr, C1D8 168hr, C1D15 336hr, C2D1 504hr; each cycle is 21 days
AUClast and AUCtau of PDR001 in Combination of FGF401: Phase I
Time frame: After the first dosing sample collection was at: C1D1 0hr , C1D1 1hr, C1D8 168hr, C1D15 336hr, C2D1 504hr; each cycle is 21 days
T1/2 of PDR001: Phase I
Time frame: After the first dosing sample collection was at: C1D1 0hr , C1D1 1hr, C1D8 168hr, C1D15 336hr, C2D1 504hr; each cycle is 21 days
Cmax of FGF401: Phase I
Time frame: C1D1 (0 hour (h), 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h), C1D8 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h), and C2D1 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h)
Cmax of FGF401 in Combination With PDR001: Phase I
Time frame: C1D1 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h)
AUCinf, AUClast & AUCtau of FGF401: Phase I
Time frame: C1D1 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h), C1D8 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h), and C2D1 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h)
AUCinf, AUClast & AUCtau of FGF401 in Combination With PDR001: Phase I
Time frame: C1D1 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h)
T1/2 of FGF401: Phase I
Time frame: C1D1 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h), C1D8 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h), and C2D1 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35655320Chan 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.
- Derived from this study: PubMed 25614940Castanon 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.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
27 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing FGF401 and PDR001 in people with Hepatocellular Carcinoma (HCC) and Solid Malignancies, run by Novartis Pharmaceuticals at 27 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in France, Germany, United States, South Korea, Spain and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only (time frame: Cycle 1 (C1) (21 days) for FGF401 single agent, Cycle 1 and Cycle 2 (C2) (42 days) for FGF401 and PDR001 combination). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02325739, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2024; AzTrials last refreshed its copy on 6 Nov 2026.