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

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT02325739
Collaborator
(none)
172
Enrollment
27
Locations
11
Arms
53
Actual Duration (Months)
6.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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

Study Type:
Interventional
Actual Enrollment :
172 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Dec 29, 2014
Actual Primary Completion Date :
May 30, 2019
Actual Study Completion Date :
May 30, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Phase I: FGF401 50 mg fasted

Participants received single agent FGF401 50 mg while fasted

Drug: FGF401
FGF401 is a FGFR4 inhibitor.
Experimental: Phase I: FGF401 80 mg fasted

Participants received single agent FGF401 80 mg while fasted

Drug: FGF401
FGF401 is a FGFR4 inhibitor.
Experimental: Phase I: FGF401 80 mg fed

Participants received single agent FGF401 80 mg while fed

Drug: FGF401
FGF401 is a FGFR4 inhibitor.
Experimental: Phase I: FGF401 120 mg fasted

Participants received single agent FGF401 120 mg while fasted

Drug: FGF401
FGF401 is a FGFR4 inhibitor.
Experimental: Phase I: FGF401 120 mg fed

Participants received single agent FGF401 120 mg while fed

Drug: FGF401
FGF401 is a FGFR4 inhibitor.
Experimental: Phase I: FGF401 150 mg fasted

Participants received single agent FGF401 150 mg while fasted

Drug: FGF401
FGF401 is a FGFR4 inhibitor.
Experimental: Phase I: FGF401 80 mg + PDR001 300 mg

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

Drug: FGF401
FGF401 is a FGFR4 inhibitor.

Biological: PDR001
PDR001 is a humanized anti-PD1 IgG4 antibody that blocks the binding of PD-L1 and PD-L2
Experimental: Phase I: FGF401 120 mg + PDR001 300 mg

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

Drug: FGF401
FGF401 is a FGFR4 inhibitor.

Biological: PDR001
PDR001 is a humanized anti-PD1 IgG4 antibody that blocks the binding of PD-L1 and PD-L2
Experimental: Phase II: Group 1 - FGF401 120 mg QD

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

Drug: FGF401
FGF401 is a FGFR4 inhibitor.
Experimental: Phase II: Group 2 - FGF401 120 mg QD

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

Drug: FGF401
FGF401 is a FGFR4 inhibitor.
Experimental: Phase II: Group 3 - FGF401 120 mg QD

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
FGF401 is a FGFR4 inhibitor.

Outcome Measures

Primary Outcome Measures

  1. Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only [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.

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

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

Secondary Outcome Measures

  1. Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II [approx. 4.5 years]

    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.

  2. Overall Response Rate (ORR) by Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1 & 2 [approx. 4.5 years]

    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)

  3. Disease Control Rate (DCR) by Local Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1, 2 & 3 [approx. 4.5 years]

    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).

  4. 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]

    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.

  5. 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]

    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.

  6. Progression-free Survival (PFS) - FGF401 Single Agent Phase II: Group 3 [4.5 years]

    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.

  7. Presence and/or Concentration of Anti-PDR001 Antibodies [Day 1 of Cycle 1 to 6, approx. 10 months after C1D1 and 150-day safety follow up (FU)]

    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.

  8. Cmax of PDR001 in Combination With FGF401: Phase I [After the first dosing sample collection was at: C1D1 0hr , C1D1 1hr, C1D8 168hr, C1D15 336hr, C2D1 504hr; each cycle is 21 days]

    Cmax is the maximum (peak) observed plasma drug concentration (mass x volume-1)

  9. AUClast and AUCtau of PDR001 in Combination of FGF401: Phase I [After the first dosing sample collection was at: C1D1 0hr , C1D1 1hr, C1D8 168hr, C1D15 336hr, C2D1 504hr; each cycle is 21 days]

    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)

  10. T1/2 of PDR001: Phase I [After the first dosing sample collection was at: C1D1 0hr , C1D1 1hr, C1D8 168hr, C1D15 336hr, C2D1 504hr; each cycle is 21 days]

    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.

  11. Cmax of FGF401: Phase I [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 is the maximum (peak) observed plasma drug concentration (mass x volume-1)

  12. Cmax of FGF401 in Combination With PDR001: Phase I [C1D1 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h)]

    Cmax is the maximum (peak) observed plasma drug concentration (mass x volume-1)

  13. AUCinf, AUClast & AUCtau of FGF401: Phase I [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: 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)

  14. AUCinf, AUClast & AUCtau of FGF401 in Combination With PDR001: Phase I [C1D1 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h)]

    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)

  15. T1/2 of FGF401: Phase I [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)]

    The elimination half-life associated with the terminal slope ( z) of a semi logarithmic concentration-time curve (time).

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  1. ECOG Performance Status ≤ 1

  2. 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

Exclusion Criteria:

  1. Previous treatment with a selective FGF19-FGFR4 targeted therapy and/or pan-FGFR inhibitor.

  2. Symptomatic CNS metastases which are neurologically unstable or requiring increasing doses of steroids to control their CNS disease.

  3. 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

  1. Pregnant or nursing (lactating) women.

Other protocol-defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of California at Los Angeles Santa Monica Location Los Angeles California United States 90095
2 Massachusetts General Hospital Oncology Dept Boston Massachusetts United States 02114
3 University of Texas MD Anderson Cancer Center Houston Texas United States 77030
4 Novartis Investigative Site Shanghai Shanghai China 200032
5 Novartis Investigative Site Rennes Cedex Ille Et Vilaine France 35062
6 Novartis Investigative Site Lille Cedex France 59037
7 Novartis Investigative Site Montpellier cedex 5 France 34295
8 Novartis Investigative Site Pessac Cedex France 33604
9 Novartis Investigative Site Toulouse Cedex 9 France 31059
10 Novartis Investigative Site Essen Germany 45147
11 Novartis Investigative Site Hannover Germany 30625
12 Novartis Investigative Site Heidelberg Germany 69120
13 Novartis Investigative Site Wuerzburg Germany 97080
14 Novartis Investigative Site Hong Kong Hong Kong
15 Novartis Investigative Site Milano MI Italy 20132
16 Novartis Investigative Site Modena MO Italy 41124
17 Novartis Investigative Site Osaka Sayama Osaka Japan 589 8511
18 Novartis Investigative Site Chuo ku Tokyo Japan 104 0045
19 Novartis Investigative Site Seoul Korea Korea, Republic of 05505
20 Novartis Investigative Site Seoul Korea, Republic of 03080
21 Novartis Investigative Site Seoul Korea, Republic of 06351
22 Novartis Investigative Site Singapore Singapore 169610
23 Novartis Investigative Site Barcelona Catalunya Spain 08035
24 Novartis Investigative Site Barcelona Catalunya Spain 08036
25 Novartis Investigative Site Madrid Spain 28034
26 Novartis Investigative Site Tainan Taiwan ROC Taiwan 70403
27 Novartis Investigative Site Taipei Taiwan 10002

Sponsors and Collaborators

  • Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02325739
Other Study ID Numbers:
  • CFGF401X2101
  • 2014-002929-35
First Posted:
Dec 25, 2014
Last Update Posted:
Dec 17, 2020
Last Verified:
Nov 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Novartis Pharmaceuticals
FGF401
PDR001
PD-1
FGFR4
FGF19
HCC
solid malignancies characterized by positive FGFR4 and KLB expression
Additional relevant MeSH terms:
Carcinoma
Neoplasms
Carcinoma, Hepatocellular
Spartalizumab

Study Results

Participant Flow

Recruitment Details 160 subjects were enrolled & treated with FGF401 single agent. In the Phase I part 74 subjects & 86 subjects in the Phase II part. 12 subjects were treated in the Phase I of the combination of FGF401 and PDR001. All subjects completed the study as per protocol & reasons for discontinuation of treatment are provided in the 'Not Completed' section.
Pre-assignment Detail At least 21 evaluable subjects were to be treated in Phase I for the model to have reasonable operating characteristics relating to its MTD &/or RP2D. Each group in the Phase II dose expansion targeted a different number of subjects. Group 1 & Group 2 planned to enroll around 40 subjects each & Group 3 planned to enroll approximately 20 subjects.
Arm/Group Title Phase I: 50 mg Fasted Phase I: 80 mg Fasted Phase I: 80 mg Fed Phase I: 120 mg Fasted Phase I: 120 mg Fed Phase I: 150 mg Fasted Phase I: FGF401 80 mg + PDR001 300 mg Phase I: FGF401 120 mg + PDR001 300 mg Phase II: Group 1 - FGF401 120 mg QD Phase II: Group 2 - FGF401 120 mg QD PhaseII: Group 3 - FGF401 120 mg QD
Arm/Group Description Participants received single agent FGF401 50 mg while fasted Participants received single agent FGF401 80 mg while fasted Participants received single agent FGF401 80 mg while fed Participants received single agent FGF401 120 mg while fasted Participants received single agent FGF401 120 mg while fed Participants received single agent FGF401 150 mg while fasted Participants received FGF401 80 mg in combination with PDR001 300 mg while fasted Participants received FGF401 120 mg in combination with PDR001 300 mg while fasted Group 1 was comprised of HCC participants from Asian contrives who took single agent FGF401 120 mg QD while fasted Group 2 was comprised of HCC participants from non-Asian countries who took single agent FGF401 120 mg QD while fasted Group 3 was comprised of participants with other solid malignancies regardless of geography who took single agent FGF401 120 mg QD while fasted
Period Title: Phase I Part
STARTED 11 6 5 26 19 7 6 6 0 0 0
COMPLETED 0 0 0 0 0 0 0 0 0 0 0
NOT COMPLETED 11 6 5 26 19 7 6 6 0 0 0
Period Title: Phase I Part
STARTED 0 0 0 0 0 0 0 0 30 36 20
COMPLETED 0 0 0 0 0 0 0 0 0 0 0
NOT COMPLETED 0 0 0 0 0 0 0 0 30 36 20

Baseline Characteristics

Arm/Group Title Phase I: 50 mg Fasted Phase I: 80 mg Fasted Phase I: 80 mg Fed Phase I: 120 mg Fasted Phase I: 120 mg Fed Phase I: 150 mg Fasted Phase I: FGF401 80 mg + PDR001 300 mg Phase I: FGF401 120 mg + PDR001 300 mg Phase II: Group 1 - FGF401 120 mg QD Phase II: Group 2 - FGF401 120 mg QD PhaseII: Group 3 - FGF401 120 mg QD Total
Arm/Group Description Participants received single agent FGF401 50 mg while fasted Participants received single agent FGF401 80 mg while fasted Participants received single agent FGF401 80 mg while fed Participants received single agent FGF401 120 mg while fasted Participants received single agent FGF401 120 mg while fed Participants received single agent FGF401 150 mg while fasted Participants received FGF401 80 mg in combination with PDR001 300 mg while fasted Participants received FGF401 120 mg in combination with PDR001 300 mg while fasted Group 1 was comprised of HCC participants from Asian contrives who took single agent FGF401 120 mg QD while fasted Group 2 was comprised of HCC participants from non-Asian countries who took single agent FGF401 120 mg QD while fasted Group 3 was comprised of participants with other solid malignancies regardless of geography who took single agent FGF401 120 mg QD while fasted Total of all reporting groups
Overall Participants 11 6 5 26 19 7 6 6 30 36 20 172
Age, Customized (participants) [Number]
18 y - <65 y
6
54.5%
4
66.7%
3
60%
14
53.8%
12
63.2%
4
57.1%
3
50%
3
50%
22
73.3%
15
41.7%
10
50%
96
55.8%
65 y - <85 y
5
45.5%
2
33.3%
2
40%
12
46.2%
6
31.6%
3
42.9%
3
50%
3
50%
8
26.7%
21
58.3%
10
50%
75
43.6%
>=85 y
0
0%
0
0%
0
0%
0
0%
1
5.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
0.6%
Sex: Female, Male (Count of Participants)
Female
4
36.4%
1
16.7%
1
20%
3
11.5%
6
31.6%
0
0%
1
16.7%
4
66.7%
8
26.7%
7
19.4%
12
60%
47
27.3%
Male
7
63.6%
5
83.3%
4
80%
23
88.5%
13
68.4%
7
100%
5
83.3%
2
33.3%
22
73.3%
29
80.6%
8
40%
125
72.7%
Race/Ethnicity, Customized (participants) [Number]
Asian
9
81.8%
2
33.3%
2
40%
14
53.8%
10
52.6%
4
57.1%
3
50%
5
83.3%
30
100%
0
0%
2
10%
81
47.1%
Black
0
0%
0
0%
0
0%
0
0%
1
5.3%
1
14.3%
0
0%
0
0%
0
0%
0
0%
0
0%
2
1.2%
Caucasian
2
18.2%
4
66.7%
3
60%
12
46.2%
8
42.1%
1
14.3%
3
50%
1
16.7%
0
0%
21
58.3%
11
55%
66
38.4%
Not applicable
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
2.8%
0
0%
1
0.6%
Other
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
2.8%
0
0%
1
0.6%
Pacific Islander
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
2.8%
0
0%
1
0.6%
Unknown
0
0%
0
0%
0
0%
0
0%
0
0%
1
14.3%
0
0%
0
0%
0
0%
12
33.3%
7
35%
20
11.6%

Outcome Measures

1. Primary Outcome
Title Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only
Description 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 Frame Cycle 1 (C1) (21 days) for FGF401 single agent, Cycle 1 and Cycle 2 (C2) (42 days) for FGF401 and PDR001 combination

Outcome Measure Data

Analysis Population Description
Dose Determining Set: All subjects from safety set (Phase I) who either met the minimum exposure criterion and had sufficient safety evaluations or had experienced a DLT during the DLT evaluation period.
Arm/Group Title Phase I: 50 mg Fasted Phase I: 80 mg Fasted Phase I: 80 mg Fed Phase I: 120 mg Fasted Phase I: 120 mg Fed Phase I: 150 mg Fasted Phase I: FGF401 80 mg + PDR001 300 mg Phase I: FGF401 120 mg + PDR001 300 mg
Arm/Group Description Participants received single agent FGF401 50 mg while fasted Participants received single agent FGF401 80 mg while fasted Participants received single agent FGF401 80 mg while fed Participants received single agent FGF401 120 mg while fasted Participants received single agent FGF401 120 mg while fed Participants received single agent FGF401 150 mg while fasted Participants received FGF401 80 mg in combination with PDR001 300 mg while fasted Participants received FGF401 120 mg in combination with PDR001 300 mg while fasted
Measure Participants 10 6 5 23 18 7 6 6
Any Primary system organ class (SOC)
10.0
90.9%
0
0%
0
0%
4.3
16.5%
5.6
29.5%
42.9
612.9%
0
0%
0
0%
Invest.: Aspartate Aminotrans. increased
0
0%
0
0%
0
0%
4.3
16.5%
0
0%
42.9
612.9%
0
0%
0
0%
Invest.: Alanine aminotrans. increased
10.0
90.9%
0
0%
0
0%
0
0%
0
0%
14.3
204.3%
0
0%
0
0%
Invest.: Blood bilirubin increased
0
0%
0
0%
0
0%
0
0%
5.6
29.5%
0
0%
0
0%
0
0%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase I: 120 mg Fasted
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter RP2D
Estimated Value 120
Confidence Interval () %
to
Parameter Dispersion Type:
Value:
Estimation Comments The estimation parameter and recommended Phase 2 dose level for FGF401 (single agent - fasted) is 120mg.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Phase I: 120 mg Fed
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter RP2D
Estimated Value 120
Confidence Interval () %
to
Parameter Dispersion Type:
Value:
Estimation Comments The estimation parameter and recommended Phase 2 dose level for FGF401 (single agent - fed) is 120mg.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Phase I: FGF401 120 mg + PDR001 300 mg
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter RP2D
Estimated Value 120, 300
Confidence Interval () %
to
Parameter Dispersion Type:
Value:
Estimation Comments The estimation parameter and recommended Phase 2 dose level for FGF401 + PDR001 combination is for FGF401 120 mg and for PDR001 300 mg.
2. Primary Outcome
Title Time to Progression (TTP): Group 1 & Group 2 (Phase II Only)
Description 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
Time Frame approx. 4.5 years

Outcome Measure Data

Analysis Population Description
Full Analysis Set (FAS): Comprised all subjects who received at least one dose of study medication. Subjects enrolled in the Phase II part were analyzed by group.
Arm/Group Title Phase II: Group 1 - FGF401 120 mg QD Phase II: Group 2 - FGF401 120 mg QD
Arm/Group Description Group 1 was comprised of HCC participants from Asian contrives who took single agent FGF401 120 mg QD while fasted Group 2 was comprised of HCC participants from non-Asian countries who took single agent FGF401 120 mg QD while fasted
Measure Participants 30 36
Median (90% Confidence Interval) [months]
2.6
3.9
3. Primary Outcome
Title Overall Response Rate (ORR) Based on Local Assessment: Group 3 (Phase II Only)
Description 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).
Time Frame approx. 4.5 years

Outcome Measure Data

Analysis Population Description
FAS: The full analysis set (FAS) comprised all subjects who received at least one dose of study medication. Subjects enrolled in the Phase II part were analyzed by group.
Arm/Group Title PhaseII: Group 3 - FGF401 120 mg QD
Arm/Group Description Group 3 was comprised of participants with other solid malignancies regardless of geography who took single agent FGF401 120 mg QD while fasted
Measure Participants 20
Number (95% Confidence Interval) [Percentage of participants]
0
0%
4. Secondary Outcome
Title Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II
Description 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.
Time Frame approx. 4.5 years

Outcome Measure Data

Analysis Population Description
FAS: The full analysis set (FAS) comprised all subjects who received at least one dose of study medication. Subjects enrolled in the Phase I part were analyzed according to the treatment they had been assigned to. Subjects enrolled in the Phase II part were analyzed by group.
Arm/Group Title Phase I: 50 mg Fasted Phase I: 80 mg Fasted Phase I: 80 mg Fed Phase I: 120 mg Fasted Phase I: 120 mg Fed Phase I: 150 mg Fasted Phase I: FGF401 80 mg + PDR001 300 mg Phase I: FGF401 120 mg + PDR001 300 mg Phase II: Group 1 - FGF401 120 mg QD Phase II: Group 2 - FGF401 120 mg QD PhaseII: Group 3 - FGF401 120 mg QD
Arm/Group Description Participants received single agent FGF401 50 mg while fasted Participants received single agent FGF401 80 mg while fasted Participants received single agent FGF401 80 mg while fed Participants received single agent FGF401 120 mg while fasted Participants received single agent FGF401 120 mg while fed Participants received single agent FGF401 150 mg while fasted Participants received FGF401 80 mg in combination with PDR001 300 mg while fasted Participants received FGF401 120 mg in combination with PDR001 300 mg while fasted Group 1 was comprised of HCC participants from Asian contrives who took single agent FGF401 120 mg QD while fasted Group 2 was comprised of HCC participants from non-Asian countries who took single agent FGF401 120 mg QD while fasted Group 3 was comprised of participants with other solid malignancies regardless of geography who took single agent FGF401 120 mg QD while fasted
Measure Participants 11 6 5 26 19 7 6 6 30 36 20
Complete Response
0
0%
0
0%
0
0%
1
3.8%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Partial Response
0
0%
1
16.7%
1
20%
0
0%
0
0%
1
14.3%
1
16.7%
1
16.7%
2
6.7%
2
5.6%
0
0%
Stable Disease
2
18.2%
1
16.7%
2
40%
12
46.2%
9
47.4%
4
57.1%
2
33.3%
2
33.3%
11
36.7%
20
55.6%
6
30%
Progressive Disease
7
63.6%
4
66.7%
1
20%
11
42.3%
8
42.1%
2
28.6%
3
50%
1
16.7%
16
53.3%
6
16.7%
12
60%
Unknown
2
18.2%
0
0%
1
20%
2
7.7%
2
10.5%
0
0%
0
0%
2
33.3%
1
3.3%
8
22.2%
2
10%
5. Secondary Outcome
Title Overall Response Rate (ORR) by Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1 & 2
Description 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)
Time Frame approx. 4.5 years

Outcome Measure Data

Analysis Population Description
FAS: The FAS comprised all subjects who received at least one dose of study medication. Subjects enrolled in the Phase I part were analyzed according to the treatment they had been assigned to. Subjects enrolled in the Phase II part were analyzed by group.
Arm/Group Title Phase I: 50 mg Fasted Phase I: 80 mg Fasted Phase I: 80 mg Fed Phase I: 120 mg Fasted Phase I: 120 mg Fed Phase I: 150 mg Fasted Phase I: FGF401 80 mg + PDR001 300 mg Phase I: FGF401 120 mg + PDR001 300 mg Phase II: Group 1 - FGF401 120 mg QD Phase II: Group 2 - FGF401 120 mg QD PhaseII: Group 3 - FGF401 120 mg QD
Arm/Group Description Participants received single agent FGF401 50 mg while fasted Participants received single agent FGF401 80 mg while fasted Participants received single agent FGF401 80 mg while fed Participants received single agent FGF401 120 mg while fasted Participants received single agent FGF401 120 mg while fed Participants received single agent FGF401 150 mg while fasted Participants received FGF401 80 mg in combination with PDR001 300 mg while fasted Participants received FGF401 120 mg in combination with PDR001 300 mg while fasted Group 1 was comprised of HCC participants from Asian contrives who took single agent FGF401 120 mg QD while fasted Group 2 was comprised of HCC participants from non-Asian countries who took single agent FGF401 120 mg QD while fasted Group 3 was comprised of participants with other solid malignancies regardless of geography who took single agent FGF401 120 mg QD while fasted
Measure Participants 11 6 5 26 19 7 6 6 30 36 0
Number (95% Confidence Interval) [Percentage of participants]
0
0%
16.7
278.3%
20.0
400%
3.8
14.6%
0
0%
14.3
204.3%
16.7
278.3%
16.7
278.3%
6.7
22.3%
5.6
15.6%
6. Secondary Outcome
Title Disease Control Rate (DCR) by Local Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1, 2 & 3
Description 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).
Time Frame approx. 4.5 years

Outcome Measure Data

Analysis Population Description
FAS: The FAS comprised all subjects who received at least one dose of study medication. Subjects enrolled in the Phase I part were analyzed according to the treatment they had been assigned to. Subjects enrolled in the Phase II part were analyzed by group.
Arm/Group Title Phase I: 50 mg Fasted Phase I: 80 mg Fasted Phase I: 80 mg Fed Phase I: 120 mg Fasted Phase I: 120 mg Fed Phase I: 150 mg Fasted Phase I: FGF401 80 mg + PDR001 300 mg Phase I: FGF401 120 mg + PDR001 300 mg Phase II: Group 1 - FGF401 120 mg QD Phase II: Group 2 - FGF401 120 mg QD PhaseII: Group 3 - FGF401 120 mg QD
Arm/Group Description Participants received single agent FGF401 50 mg while fasted Participants received single agent FGF401 80 mg while fasted Participants received single agent FGF401 80 mg while fed Participants received single agent FGF401 120 mg while fasted Participants received single agent FGF401 120 mg while fed Participants received single agent FGF401 150 mg while fasted Participants received FGF401 80 mg in combination with PDR001 300 mg while fasted Participants received FGF401 120 mg in combination with PDR001 300 mg while fasted Group 1 was comprised of HCC participants from Asian contrives who took single agent FGF401 120 mg QD while fasted Group 2 was comprised of HCC participants from non-Asian countries who took single agent FGF401 120 mg QD while fasted Group 3 was comprised of participants with other solid malignancies regardless of geography who took single agent FGF401 120 mg QD while fasted
Measure Participants 11 6 5 26 19 7 6 6 30 36 20
Number (95% Confidence Interval) [percentage of participants]
18.2
165.5%
33.3
555%
60.0
1200%
50.0
192.3%
47.4
249.5%
71.4
1020%
50.0
833.3%
50.0
833.3%
43.3
144.3%
61.1
169.7%
30.0
150%
7. Secondary Outcome
Title 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)
Description 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.
Time Frame approx. 4.5 years

Outcome Measure Data

Analysis Population Description
The full analysis set (FAS) comprised all subjects who received at least one dose of study medication. Subjects enrolled in the Phase I part were analyzed according to the treatment they had been assigned to.
Arm/Group Title Phase I: 120 mg Fasted Phase I: 120 mg Fed Phase I: FGF401 120 mg + PDR001 300 mg
Arm/Group Description Participants received single agent FGF401 120 mg while fasted Participants received single agent FGF401 120 mg while fed Participants received FGF401 120 mg in combination with PDR001 300 mg while fasted
Measure Participants 26 19 6
Median (90% Confidence Interval) [months]
4.1
2.0
5.3
8. Secondary Outcome
Title 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)
Description 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.
Time Frame start of treatment to death, up to about 53 months

Outcome Measure Data

Analysis Population Description
FAS: The full analysis set (FAS) comprised all subjects who received at least one dose of study medication. Subjects enrolled in the Phase I part were analyzed according to the treatment they had been assigned to. Subjects enrolled in the Phase II part were analyzed by group.
Arm/Group Title Phase I: 120 mg Fasted Phase I: 120 mg Fed Phase I: FGF401 120 mg + PDR001 300 mg Phase II: Group 1 - FGF401 120 mg QD Phase II: Group 2 - FGF401 120 mg QD PhaseII: Group 3 - FGF401 120 mg QD
Arm/Group Description Participants received single agent FGF401 120 mg while fasted Participants received single agent FGF401 120 mg while fed Participants received FGF401 120 mg in combination with PDR001 300 mg while fasted Group 1 was comprised of HCC participants from Asian contrives who took single agent FGF401 120 mg QD while fasted Group 2 was comprised of HCC participants from non-Asian countries who took single agent FGF401 120 mg QD while fasted Group 3 was comprised of participants with other solid malignancies regardless of geography who took single agent FGF401 120 mg QD while fasted
Measure Participants 26 19 6 30 36 20
Median (90% Confidence Interval) [months]
7.0
4.9
NA
5.9
10.9
6.2
9. Secondary Outcome
Title Progression-free Survival (PFS) - FGF401 Single Agent Phase II: Group 3
Description 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.
Time Frame 4.5 years

Outcome Measure Data

Analysis Population Description
Full Analysis Set (FAS): Comprised all subjects who received at least one dose of study medication. Subjects enrolled in the Phase II part were analyzed by group.
Arm/Group Title PhaseII: Group 3 - FGF401 120 mg QD
Arm/Group Description Group 3 was comprised of participants with other solid malignancies regardless of geography who took single agent FGF401 120 mg QD while fasted
Measure Participants 20
Median (95% Confidence Interval) [months]
1.4
10. Secondary Outcome
Title Presence and/or Concentration of Anti-PDR001 Antibodies
Description 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.
Time Frame Day 1 of Cycle 1 to 6, approx. 10 months after C1D1 and 150-day safety follow up (FU)

Outcome Measure Data

Analysis Population Description
FAS: The full analysis set (FAS) comprised all subjects who received at least one dose of study medication. Subjects enrolled in the Phase I part were analyzed according to the treatment they had been assigned to.
Arm/Group Title Phase II: Group 1 - FGF401 120 mg QD Phase I: FGF401 120 mg + PDR001 300 mg
Arm/Group Description Group 1 was comprised of HCC participants from Asian contrives who took single agent FGF401 120 mg QD while fasted Participants received FGF401 120 mg in combination with PDR001 300 mg while fasted
Measure Participants 6 6
ADA-negative
100.0
909.1%
83.3
1388.3%
ADA-positive (i.e. ADA incidence)
0
0%
16.7
278.3%
Treatment-induced ADA-positive
0
0%
20.0
333.3%
Treatment-boosted ADA-positive
0
0%
0
0%
11. Secondary Outcome
Title Cmax of PDR001 in Combination With FGF401: Phase I
Description Cmax is the maximum (peak) observed plasma drug concentration (mass x volume-1)
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

Outcome Measure Data

Analysis Population Description
The PAS included all subjects who provided at least one evaluable drug concentration. For those requiring non-compartment analyses, the PAS included all subjects who provided an evaluable PK profile.
Arm/Group Title Phase II: Group 1 - FGF401 120 mg QD Phase I: FGF401 120 mg + PDR001 300 mg
Arm/Group Description Group 1 was comprised of HCC participants from Asian contrives who took single agent FGF401 120 mg QD while fasted Participants received FGF401 120 mg in combination with PDR001 300 mg while fasted
Measure Participants 6 6
Geometric Mean (Geometric Coefficient of Variation) [μg/mL]
74.7
(43.0)
87.7
(5.4)
12. Secondary Outcome
Title AUClast and AUCtau of PDR001 in Combination of FGF401: Phase I
Description 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)
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

Outcome Measure Data

Analysis Population Description
The PAS included all subjects who provided at least one evaluable drug concentration. For those requiring non-compartment analyses, the PAS included all subjects who provided an evaluable PK profile
Arm/Group Title Phase II: Group 1 - FGF401 120 mg QD Phase I: FGF401 120 mg + PDR001 300 mg
Arm/Group Description Group 1 was comprised of HCC participants from Asian contrives who took single agent FGF401 120 mg QD while fasted Participants received FGF401 120 mg in combination with PDR001 300 mg while fasted
Measure Participants 6 6
AUClast
795
(34.5)
978
(15.8)
AUC0-504h
760
(1.9)
967
(13.9)
13. Secondary Outcome
Title T1/2 of PDR001: Phase I
Description 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.
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

Outcome Measure Data

Analysis Population Description
The PAS incl. all subjects who provided at least one evaluable drug concentration. For those requiring non-compartment analyses, PAS incl. all subjects who provided an evaluable PK profile. Due to the sparse PK sampling designed for PDR001, PDR001 concentration data was insufficient for accurate estimation of secondary PK parameters including T1/2.
Arm/Group Title Phase II: Group 1 - FGF401 120 mg QD Phase I: FGF401 120 mg + PDR001 300 mg
Arm/Group Description Group 1 was comprised of HCC participants from Asian contrives who took single agent FGF401 120 mg QD while fasted Participants received FGF401 120 mg in combination with PDR001 300 mg while fasted
Measure Participants 0 0
14. Secondary Outcome
Title Cmax of FGF401: Phase I
Description Cmax is the maximum (peak) observed plasma drug concentration (mass x volume-1)
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)

Outcome Measure Data

Analysis Population Description
The PAS included all subjects who provided at least one evaluable drug concentration. For those requiring non-compartment analyses, the PAS included all subjects who provided an evaluable PK profile.
Arm/Group Title Phase I: 50 mg Fasted Phase I: 80 mg Fasted Phase I: 80 mg Fed Phase I: 120 mg Fasted Phase I: 120 mg Fed Phase I: 150 mg Fasted
Arm/Group Description Participants received single agent FGF401 50 mg while fasted Participants received single agent FGF401 80 mg while fasted Participants received single agent FGF401 80 mg while fed Participants received single agent FGF401 120 mg while fasted Participants received single agent FGF401 120 mg while fed Participants received single agent FGF401 150 mg while fasted
Measure Participants 10 6 5 26 19 7
Cycle 1 Day 1
698
(36.1)
967
(25.0)
659
(15.2)
1090
(37.9)
1050
(32.3)
1400
(32.1)
Cycle 1 Day 8
663
(46.8)
838
(16.5)
704
(22.1)
1120
(36.5)
1060
(22.1)
1070
(46.0)
Cycle 2 Day 1
696
(44.2)
786
(25.5)
703
(41.7)
1070
(32.2)
1000
(23.9)
1350
(28.1)
15. Secondary Outcome
Title Cmax of FGF401 in Combination With PDR001: Phase I
Description Cmax is the maximum (peak) observed plasma drug concentration (mass x volume-1)
Time Frame C1D1 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h)

Outcome Measure Data

Analysis Population Description
The PAS included all subjects who provided at least one evaluable drug concentration. For those requiring non-compartment analyses, the PAS included all subjects who provided an evaluable PK profile.
Arm/Group Title Phase II: Group 1 - FGF401 120 mg QD Phase I: FGF401 120 mg + PDR001 300 mg
Arm/Group Description Group 1 was comprised of HCC participants from Asian contrives who took single agent FGF401 120 mg QD while fasted Participants received FGF401 120 mg in combination with PDR001 300 mg while fasted
Measure Participants 6 6
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
732
(26.8)
1450
(31.4)
16. Secondary Outcome
Title AUCinf, AUClast & AUCtau of FGF401: Phase I
Description 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)
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)

Outcome Measure Data

Analysis Population Description
The PAS included all subjects who provided at least one evaluable drug concentration. For those requiring non-compartment analyses, the PAS included all subjects who provided an evaluable PK profile.
Arm/Group Title Phase I: 50 mg Fasted Phase I: 80 mg Fasted Phase I: 80 mg Fed Phase I: 120 mg Fasted Phase I: 120 mg Fed Phase I: 150 mg Fasted
Arm/Group Description Participants received single agent FGF401 50 mg while fasted Participants received single agent FGF401 80 mg while fasted Participants received single agent FGF401 80 mg while fed Participants received single agent FGF401 120 mg while fasted Participants received single agent FGF401 120 mg while fed Participants received single agent FGF401 150 mg while fasted
Measure Participants 10 6 5 26 19 7
AUCinf C1D1
4920
(51.9)
5090
(32.9)
5560
(23.1)
7210
(35.4)
8520
(35.2)
8190
(42.7)
AUClast C1D1
4610
(50.4)
4710
(38.0)
4600
(39.2)
6710
(35.6)
7850
(34.1)
7920
(42.0)
AUCtau C1D1
4610
(50.4)
4910
(30.3)
4860
(29.4)
6840
(33.6)
8020
(33.5)
7930
(41.8)
AUCinf C1D8
3650
(71.9)
5130
(28.9)
5550
(23.2)
7590
(43.0)
7980
(25.1)
7850
(29.4)
AUClast C1D8
3460
(62.5)
4840
(27.0)
5280
(23.9)
6480
(47.5)
7640
(33.1)
7550
(28.6)
AUCtau C1D8
3650
(65.6)
4850
(27.0)
5290
(24.0)
6970
(38.7)
7330
(26.7)
7510
(29.8)
AUCinf C2D1
4390
(54.0)
4580
(30.6)
5110
(44.3)
7770
(33.2)
8760
(23.5)
7850
(25.7)
AUClast C2D1
4100
(52.9)
4210
(32.5)
4880
(43.1)
7260
(33.6)
7520
(38.7)
7610
(25.8)
AUCtau C2D1
4100
(52.7)
4360
(28.5)
4870
(43.7)
7330
(31.7)
7830
(23.4)
7620
(25.7)
17. Secondary Outcome
Title AUCinf, AUClast & AUCtau of FGF401 in Combination With PDR001: Phase I
Description 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)
Time Frame C1D1 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h)

Outcome Measure Data

Analysis Population Description
The PAS included all subjects who provided at least one evaluable drug concentration. For those requiring non-compartment analyses, the PAS included all subjects who provided an evaluable PK profile.
Arm/Group Title Phase II: Group 1 - FGF401 120 mg QD Phase I: FGF401 120 mg + PDR001 300 mg
Arm/Group Description Group 1 was comprised of HCC participants from Asian contrives who took single agent FGF401 120 mg QD while fasted Participants received FGF401 120 mg in combination with PDR001 300 mg while fasted
Measure Participants 6 6
AUCinf
5030
(25.5)
7540
(37.0)
AUClast
4760
(25.0)
7280
(36.7)
AUCtau
4770
(24.4)
7280
(36.7)
18. Secondary Outcome
Title T1/2 of FGF401: Phase I
Description The elimination half-life associated with the terminal slope ( z) of a semi logarithmic concentration-time curve (time).
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)

Outcome Measure Data

Analysis Population Description
The PAS included all subjects who provided at least one evaluable drug concentration. For those requiring non-compartment analyses, the PAS included all subjects who provided an evaluable PK profile.
Arm/Group Title Phase I: 50 mg Fasted Phase I: 80 mg Fasted Phase I: 80 mg Fed Phase I: 120 mg Fasted Phase I: 120 mg Fed Phase I: 150 mg Fasted
Arm/Group Description Participants received single agent FGF401 50 mg while fasted Participants received single agent FGF401 80 mg while fasted Participants received single agent FGF401 80 mg while fed Participants received single agent FGF401 120 mg while fasted Participants received single agent FGF401 120 mg while fed Participants received single agent FGF401 150 mg while fasted
Measure Participants 10 6 5 26 19 7
C1D1
6.27
(16.2)
4.91
(31.6)
5.2
(8.8)
5.47
(14.4)
5.16
(16.3)
5
(11.3)
C1D8
6.57
(16.6)
6.08
(13.8)
5.58
(12.0)
5.43
(30.0)
5.58
(17.1)
5.24
(12.4)
C2D1
6.46
(18.9)
5.44
(34.9)
5.43
(17.2)
5.8
(22.1)
5.81
(20.2)
4.92
(14.4)
19. Post-Hoc Outcome
Title All Collected Deaths
Description This includes on-treatment deaths collected from first patient first treatment up to 30 days after drug discontinuation for a maximum of approx. 135.3 weeks (treatment duration ranged from 0.1 to 135.3 weeks for FGF401 single agent and from 6.0 to 57.0 weeks for FGF401 plus PDR001 combination). Deaths post treatment survival follow up were collected after the on treatment period, up to approx. 4.5 years. Participants who had not died after study drug discontinuation were censored at the last date when the participant had some documented personal contact (visit or phone call) with the investigator.
Time Frame approx. 135.3 weeks, approx. 4.5 years

Outcome Measure Data

Analysis Population Description
FAS: The full analysis set (FAS) comprised all subjects who received at least one dose of study medication. Subjects enrolled in the Phase II part were analyzed by group.
Arm/Group Title Phase I: 50 mg Fasted Phase I: 80 mg Fasted Phase I: 80 mg Fed Phase I: 120 mg Fasted Phase I: 120 mg Fed Phase I: 150 mg Fasted Phase II: Group 1 - FGF401 120 mg QD Phase II: Group 2 - FGF401 120 mg QD Phase II: Group 3 - FGF401 120 mg QD All Patients of Single Agent FGF401 Phase I: FGF401 80 mg + PDR001 300 mg Phase I: FGF401 120 mg + PDR001 300 mg All Patients of Combination Dose All Patients
Arm/Group Description Participants received single agent FGF401 50 mg while fasted Participants received single agent FGF401 80 mg while fasted Participants received single agent FGF401 80 mg while fed Participants received single agent FGF401 120 mg while fasted Participants received single agent FGF401 120 mg while fed Participants received single agent FGF401 150 mg while fasted Group 1 was comprised of HCC participants from Asian contrives who took single agent FGF401 120 mg QD while fasted Group 2 was comprised of HCC participants from non-Asian countries who took single agent FGF401 120 mg QD while fasted Group 3 was comprised of participants with other solid malignancies regardless of geography who took single agent FGF401 120 mg QD while fasted These were all the participants who received single dose of FGF401 Participants received FGF401 80 mg in combination with PDR001 300 mg while fasted Participants received FGF401 120 mg in combination with PDR001 300 mg while fasted These were all the participants in the Phase I part who received combination dose of FGF401 and PDR001 Overall participants in the in Phase I & Phase II of study
Measure Participants 11 6 5 26 19 7 30 36 20 160 6 6 12 172
Total deaths
10
90.9%
5
83.3%
3
60%
23
88.5%
12
63.2%
4
57.1%
20
333.3%
22
366.7%
16
53.3%
115
319.4%
2
10%
2
1.2%
4
NaN
119
NaN
Deaths on-treatment
2
18.2%
1
16.7%
0
0%
4
15.4%
6
31.6%
1
14.3%
2
33.3%
2
33.3%
2
6.7%
20
55.6%
0
0%
0
0%
0
NaN
20
NaN
Deaths post-treatment survival follow up
8
72.7%
4
66.7%
3
60%
19
73.1%
6
31.6%
3
42.9%
18
300%
20
333.3%
14
46.7%
95
263.9%
2
10%
2
1.2%
4
NaN
99
NaN

Adverse Events

Time Frame This includes on-treatment deaths collected from first patient first treatment up to 30 days after drug discontinuation for a maximum of 135.3 weeks (treatment duration ranged from 0.1 to 135.3 weeks for FGF401 single agent and from 6.0 to 57.0 weeks for FGF401 plus PDR001 combination).
Adverse Event Reporting Description Adverse Event (AE): Any sign or symptom that occurs during the study treatment plus the 30 or 150 days post treatment depending on single dose or combination dose.
Arm/Group Title Phase I: 50 mg Fasted Phase I: 80 mg Fasted Phase I: 80 mg Fed Phase I: 120 mg Fasted Phase I: 120 mg Fed Phase I: 150 mg Fasted Phase II: Group 1 - FGF401 120 mg QD Phase II: Group 2 - FGF401 120 mg QD Phase II: Group 3 - FGF401 120 mg QD All Patients of Single Agent FGF401 Phase I: FGF401 80 mg + PDR001 300 mg Phase I: FGF401 120 mg + PDR001 300 mg All Patients of Combination Dose All Patients
Arm/Group Description Participants received single agent FGF401 50 mg while fasted Participants received single agent FGF401 80 mg while fasted Participants received single agent FGF401 80 mg while fed Participants received single agent FGF401 120 mg while fasted Participants received single agent FGF401 120 mg while fed Participants received single agent FGF401 150 mg while fasted Group 1 was comprised of HCC participants from Asian contrives who took single agent FGF401 120 mg QD while fasted Group 2 was comprised of HCC participants from non-Asian countries who took single agent FGF401 120 mg QD while fasted Group 3 was comprised of participants with other solid malignancies regardless of geography who took single agent FGF401 120 mg QD while fasted These were all the participants who received single dose of FGF401 Participants received FGF401 80 mg in combination with PDR001 300 mg while fasted Participants received FGF401 120 mg in combination with PDR001 300 mg while fasted These were all the participants in the Phase I part who received combination dose of FGF401 and PDR001 Overall participants in the in Phase I & Phase II of study
All Cause Mortality
Phase I: 50 mg Fasted Phase I: 80 mg Fasted Phase I: 80 mg Fed Phase I: 120 mg Fasted Phase I: 120 mg Fed Phase I: 150 mg Fasted Phase II: Group 1 - FGF401 120 mg QD Phase II: Group 2 - FGF401 120 mg QD Phase II: Group 3 - FGF401 120 mg QD All Patients of Single Agent FGF401 Phase I: FGF401 80 mg + PDR001 300 mg Phase I: FGF401 120 mg + PDR001 300 mg All Patients of Combination Dose All Patients
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 2/11 (18.2%) 1/6 (16.7%) 0/5 (0%) 4/26 (15.4%) 6/19 (31.6%) 1/7 (14.3%) 2/30 (6.7%) 2/36 (5.6%) 2/20 (10%) 20/160 (12.5%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 20/172 (11.6%)
Serious Adverse Events
Phase I: 50 mg Fasted Phase I: 80 mg Fasted Phase I: 80 mg Fed Phase I: 120 mg Fasted Phase I: 120 mg Fed Phase I: 150 mg Fasted Phase II: Group 1 - FGF401 120 mg QD Phase II: Group 2 - FGF401 120 mg QD Phase II: Group 3 - FGF401 120 mg QD All Patients of Single Agent FGF401 Phase I: FGF401 80 mg + PDR001 300 mg Phase I: FGF401 120 mg + PDR001 300 mg All Patients of Combination Dose All Patients
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 3/11 (27.3%) 5/6 (83.3%) 3/5 (60%) 15/26 (57.7%) 9/19 (47.4%) 3/7 (42.9%) 15/30 (50%) 9/36 (25%) 8/20 (40%) 70/160 (43.8%) 0/6 (0%) 2/6 (33.3%) 2/12 (16.7%) 72/172 (41.9%)
Blood and lymphatic system disorders
Anaemia 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Cardiac disorders
Acute coronary syndrome 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 1/20 (5%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Coronary artery disease 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Ear and labyrinth disorders
Vertigo 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Gastrointestinal disorders
Abdominal distension 0/11 (0%) 0/6 (0%) 1/5 (20%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 1/30 (3.3%) 0/36 (0%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Abdominal pain 0/11 (0%) 0/6 (0%) 1/5 (20%) 0/26 (0%) 3/19 (15.8%) 0/7 (0%) 0/30 (0%) 2/36 (5.6%) 3/20 (15%) 9/160 (5.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 9/172 (5.2%)
Abdominal pain upper 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 1/19 (5.3%) 0/7 (0%) 1/30 (3.3%) 0/36 (0%) 0/20 (0%) 3/160 (1.9%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 3/172 (1.7%)
Ascites 1/11 (9.1%) 0/6 (0%) 1/5 (20%) 2/26 (7.7%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 5/160 (3.1%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 5/172 (2.9%)
Diarrhoea 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 2/6 (33.3%) 2/12 (16.7%) 3/172 (1.7%)
Duodenal obstruction 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 1/20 (5%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Dysphagia 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 1/20 (5%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Gastric varices 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 1/30 (3.3%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Gastritis 0/11 (0%) 0/6 (0%) 0/5 (0%) 2/26 (7.7%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Gastrointestinal haemorrhage 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Haematemesis 0/11 (0%) 1/6 (16.7%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 1/36 (2.8%) 0/20 (0%) 3/160 (1.9%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 3/172 (1.7%)
Oesophageal varices haemorrhage 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 1/7 (14.3%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 1/6 (16.7%) 1/12 (8.3%) 3/172 (1.7%)
Upper gastrointestinal haemorrhage 1/11 (9.1%) 1/6 (16.7%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 3/160 (1.9%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 3/172 (1.7%)
Vomiting 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 1/20 (5%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
General disorders
Asthenia 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 1/30 (3.3%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Chest discomfort 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 1/30 (3.3%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Fatigue 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Gait disturbance 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 1/20 (5%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Multiple organ dysfunction syndrome 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 1/36 (2.8%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Oedema peripheral 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Pyrexia 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 2/20 (10%) 3/160 (1.9%) 0/6 (0%) 2/6 (33.3%) 2/12 (16.7%) 5/172 (2.9%)
Hepatobiliary disorders
Biloma 0/11 (0%) 0/6 (0%) 1/5 (20%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Cholangitis 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 1/30 (3.3%) 0/36 (0%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Cholestasis 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Hepatic cirrhosis 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Hepatic haematoma 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 1/36 (2.8%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Hepatic pain 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 1/36 (2.8%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Hyperbilirubinaemia 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Infections and infestations
Herpes zoster 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 1/30 (3.3%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Lung infection 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Pneumonia 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 1/36 (2.8%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Pyelonephritis acute 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 1/30 (3.3%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Varicella 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 1/20 (5%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Injury, poisoning and procedural complications
Bone contusion 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Investigations
Alanine aminotransferase increased 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 1/7 (14.3%) 1/30 (3.3%) 0/36 (0%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Aspartate aminotransferase increased 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 2/7 (28.6%) 1/30 (3.3%) 0/36 (0%) 0/20 (0%) 3/160 (1.9%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 3/172 (1.7%)
Blood bilirubin increased 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 1/30 (3.3%) 0/36 (0%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Metabolism and nutrition disorders
Hypercalcaemia 0/11 (0%) 1/6 (16.7%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Hyperglycaemia 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 0/160 (0%) 0/6 (0%) 1/6 (16.7%) 1/12 (8.3%) 1/172 (0.6%)
Hypoglycaemia 0/11 (0%) 0/6 (0%) 0/5 (0%) 2/26 (7.7%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Musculoskeletal and connective tissue disorders
Back pain 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 2/36 (5.6%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Liver carcinoma ruptured 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 1/36 (2.8%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 1/6 (16.7%) 1/12 (8.3%) 2/172 (1.2%)
Tumour associated fever 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 1/7 (14.3%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Tumour thrombosis 0/11 (0%) 1/6 (16.7%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Nervous system disorders
Carotid artery stenosis 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Cerebrovascular accident 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 1/30 (3.3%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Dysarthria 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Haemorrhage intracranial 0/11 (0%) 1/6 (16.7%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Paraesthesia 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Paraparesis 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 1/30 (3.3%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Paraplegia 0/11 (0%) 1/6 (16.7%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Psychiatric disorders
Confusional state 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 1/20 (5%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Renal and urinary disorders
Acute kidney injury 0/11 (0%) 0/6 (0%) 0/5 (0%) 2/26 (7.7%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Calculus urinary 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 1/20 (5%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Urinary retention 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 1/20 (5%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Respiratory, thoracic and mediastinal disorders
Atelectasis 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 1/30 (3.3%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Bronchial obstruction 0/11 (0%) 0/6 (0%) 1/5 (20%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Bronchostenosis 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Dyspnoea 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 1/30 (3.3%) 0/36 (0%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Haemoptysis 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 1/7 (14.3%) 1/30 (3.3%) 0/36 (0%) 1/20 (5%) 4/160 (2.5%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 4/172 (2.3%)
Pleural effusion 0/11 (0%) 0/6 (0%) 0/5 (0%) 2/26 (7.7%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Pneumonitis 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Productive cough 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 1/20 (5%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Pulmonary embolism 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Vascular disorders
Aneurysm 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 1/36 (2.8%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Bleeding varicose vein 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 1/30 (3.3%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Hypovolaemic shock 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 1/36 (2.8%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Inferior vena caval occlusion 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Venous thrombosis 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 1/30 (3.3%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Other (Not Including Serious) Adverse Events
Phase I: 50 mg Fasted Phase I: 80 mg Fasted Phase I: 80 mg Fed Phase I: 120 mg Fasted Phase I: 120 mg Fed Phase I: 150 mg Fasted Phase II: Group 1 - FGF401 120 mg QD Phase II: Group 2 - FGF401 120 mg QD Phase II: Group 3 - FGF401 120 mg QD All Patients of Single Agent FGF401 Phase I: FGF401 80 mg + PDR001 300 mg Phase I: FGF401 120 mg + PDR001 300 mg All Patients of Combination Dose All Patients
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 11/11 (100%) 6/6 (100%) 5/5 (100%) 26/26 (100%) 19/19 (100%) 7/7 (100%) 29/30 (96.7%) 36/36 (100%) 20/20 (100%) 159/160 (99.4%) 6/6 (100%) 6/6 (100%) 12/12 (100%) 171/172 (99.4%)
Blood and lymphatic system disorders
Anaemia 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 3/26 (11.5%) 2/19 (10.5%) 1/7 (14.3%) 5/30 (16.7%) 1/36 (2.8%) 5/20 (25%) 18/160 (11.3%) 2/6 (33.3%) 2/6 (33.3%) 4/12 (33.3%) 22/172 (12.8%)
Hyperglobulinaemia 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 1/7 (14.3%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Leukopenia 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 1/19 (5.3%) 1/7 (14.3%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 3/160 (1.9%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 3/172 (1.7%)
Lymphopenia 0/11 (0%) 0/6 (0%) 0/5 (0%) 2/26 (7.7%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Thrombocytopenia 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Cardiac disorders
Palpitations 0/11 (0%) 0/6 (0%) 1/5 (20%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 1/6 (16.7%) 0/6 (0%) 1/12 (8.3%) 2/172 (1.2%)
Endocrine disorders
Hyperthyroidism 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 0/160 (0%) 0/6 (0%) 1/6 (16.7%) 1/12 (8.3%) 1/172 (0.6%)
Gastrointestinal disorders
Abdominal discomfort 0/11 (0%) 0/6 (0%) 1/5 (20%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 1/30 (3.3%) 0/36 (0%) 0/20 (0%) 2/160 (1.3%) 1/6 (16.7%) 0/6 (0%) 1/12 (8.3%) 3/172 (1.7%)
Abdominal distension 1/11 (9.1%) 0/6 (0%) 1/5 (20%) 3/26 (11.5%) 0/19 (0%) 3/7 (42.9%) 3/30 (10%) 1/36 (2.8%) 1/20 (5%) 13/160 (8.1%) 0/6 (0%) 3/6 (50%) 3/12 (25%) 16/172 (9.3%)
Abdominal pain 0/11 (0%) 1/6 (16.7%) 3/5 (60%) 3/26 (11.5%) 4/19 (21.1%) 0/7 (0%) 5/30 (16.7%) 6/36 (16.7%) 9/20 (45%) 31/160 (19.4%) 0/6 (0%) 2/6 (33.3%) 2/12 (16.7%) 33/172 (19.2%)
Abdominal pain upper 1/11 (9.1%) 1/6 (16.7%) 0/5 (0%) 7/26 (26.9%) 1/19 (5.3%) 0/7 (0%) 5/30 (16.7%) 5/36 (13.9%) 1/20 (5%) 21/160 (13.1%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 21/172 (12.2%)
Abdominal tenderness 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Angular cheilitis 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Ascites 0/11 (0%) 1/6 (16.7%) 2/5 (40%) 5/26 (19.2%) 0/19 (0%) 2/7 (28.6%) 4/30 (13.3%) 3/36 (8.3%) 2/20 (10%) 19/160 (11.9%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 19/172 (11%)
Constipation 1/11 (9.1%) 0/6 (0%) 1/5 (20%) 4/26 (15.4%) 1/19 (5.3%) 0/7 (0%) 5/30 (16.7%) 5/36 (13.9%) 6/20 (30%) 23/160 (14.4%) 1/6 (16.7%) 0/6 (0%) 1/12 (8.3%) 24/172 (14%)
Diarrhoea 8/11 (72.7%) 4/6 (66.7%) 4/5 (80%) 18/26 (69.2%) 14/19 (73.7%) 7/7 (100%) 23/30 (76.7%) 23/36 (63.9%) 17/20 (85%) 118/160 (73.8%) 3/6 (50%) 4/6 (66.7%) 7/12 (58.3%) 125/172 (72.7%)
Dry mouth 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 3/36 (8.3%) 1/20 (5%) 5/160 (3.1%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 5/172 (2.9%)
Duodenal ulcer 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 1/30 (3.3%) 0/36 (0%) 0/20 (0%) 3/160 (1.9%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 3/172 (1.7%)
Dyspepsia 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 4/36 (11.1%) 0/20 (0%) 4/160 (2.5%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 4/172 (2.3%)
Dysphagia 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 1/30 (3.3%) 2/36 (5.6%) 1/20 (5%) 5/160 (3.1%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 5/172 (2.9%)
Gastrointestinal haemorrhage 0/11 (0%) 1/6 (16.7%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Gastrointestinal sounds abnormal 0/11 (0%) 1/6 (16.7%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Gastrooesophageal reflux disease 0/11 (0%) 0/6 (0%) 0/5 (0%) 4/26 (15.4%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 1/36 (2.8%) 1/20 (5%) 6/160 (3.8%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 6/172 (3.5%)
Haemorrhoidal haemorrhage 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 2/20 (10%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Haemorrhoids 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 1/7 (14.3%) 0/30 (0%) 1/36 (2.8%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Melaena 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 1/7 (14.3%) 2/30 (6.7%) 0/36 (0%) 0/20 (0%) 4/160 (2.5%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 4/172 (2.3%)
Nausea 1/11 (9.1%) 1/6 (16.7%) 0/5 (0%) 5/26 (19.2%) 6/19 (31.6%) 1/7 (14.3%) 7/30 (23.3%) 6/36 (16.7%) 11/20 (55%) 38/160 (23.8%) 0/6 (0%) 2/6 (33.3%) 2/12 (16.7%) 40/172 (23.3%)
Oesophageal stenosis 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Oesophageal ulcer 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Oesophageal varices haemorrhage 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Stomatitis 2/11 (18.2%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 1/30 (3.3%) 1/36 (2.8%) 0/20 (0%) 4/160 (2.5%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 4/172 (2.3%)
Toothache 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Varices oesophageal 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Vomiting 1/11 (9.1%) 1/6 (16.7%) 1/5 (20%) 4/26 (15.4%) 6/19 (31.6%) 1/7 (14.3%) 5/30 (16.7%) 4/36 (11.1%) 9/20 (45%) 32/160 (20%) 0/6 (0%) 1/6 (16.7%) 1/12 (8.3%) 33/172 (19.2%)
General disorders
Asthenia 2/11 (18.2%) 2/6 (33.3%) 0/5 (0%) 4/26 (15.4%) 3/19 (15.8%) 2/7 (28.6%) 3/30 (10%) 6/36 (16.7%) 4/20 (20%) 26/160 (16.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 26/172 (15.1%)
Chest discomfort 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 2/30 (6.7%) 0/36 (0%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Chills 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 3/30 (10%) 0/36 (0%) 1/20 (5%) 5/160 (3.1%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 5/172 (2.9%)
Fatigue 2/11 (18.2%) 1/6 (16.7%) 0/5 (0%) 6/26 (23.1%) 4/19 (21.1%) 0/7 (0%) 2/30 (6.7%) 8/36 (22.2%) 7/20 (35%) 30/160 (18.8%) 1/6 (16.7%) 2/6 (33.3%) 3/12 (25%) 33/172 (19.2%)
General physical health deterioration 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 2/36 (5.6%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Hernia 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 1/7 (14.3%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Malaise 0/11 (0%) 0/6 (0%) 0/5 (0%) 2/26 (7.7%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 1/36 (2.8%) 0/20 (0%) 3/160 (1.9%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 3/172 (1.7%)
Oedema 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 1/36 (2.8%) 0/20 (0%) 2/160 (1.3%) 1/6 (16.7%) 0/6 (0%) 1/12 (8.3%) 3/172 (1.7%)
Oedema peripheral 0/11 (0%) 1/6 (16.7%) 0/5 (0%) 9/26 (34.6%) 0/19 (0%) 0/7 (0%) 8/30 (26.7%) 9/36 (25%) 3/20 (15%) 30/160 (18.8%) 0/6 (0%) 2/6 (33.3%) 2/12 (16.7%) 32/172 (18.6%)
Pain 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 1/7 (14.3%) 0/30 (0%) 2/36 (5.6%) 1/20 (5%) 4/160 (2.5%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 4/172 (2.3%)
Peripheral swelling 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 1/7 (14.3%) 1/30 (3.3%) 0/36 (0%) 0/20 (0%) 3/160 (1.9%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 3/172 (1.7%)
Pyrexia 3/11 (27.3%) 0/6 (0%) 2/5 (40%) 6/26 (23.1%) 1/19 (5.3%) 1/7 (14.3%) 9/30 (30%) 4/36 (11.1%) 5/20 (25%) 31/160 (19.4%) 1/6 (16.7%) 3/6 (50%) 4/12 (33.3%) 35/172 (20.3%)
Hepatobiliary disorders
Hepatic function abnormal 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Hepatic pain 0/11 (0%) 0/6 (0%) 1/5 (20%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 2/36 (5.6%) 1/20 (5%) 5/160 (3.1%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 5/172 (2.9%)
Hepatocellular injury 0/11 (0%) 0/6 (0%) 1/5 (20%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 1/36 (2.8%) 1/20 (5%) 3/160 (1.9%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 3/172 (1.7%)
Hepatomegaly 0/11 (0%) 0/6 (0%) 0/5 (0%) 2/26 (7.7%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Hepatorenal syndrome 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Hyperbilirubinaemia 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 1/20 (5%) 3/160 (1.9%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 3/172 (1.7%)
Jaundice 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 2/30 (6.7%) 1/36 (2.8%) 0/20 (0%) 3/160 (1.9%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 3/172 (1.7%)
Jaundice cholestatic 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Infections and infestations
Bronchitis 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 1/36 (2.8%) 1/20 (5%) 3/160 (1.9%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 3/172 (1.7%)
Candida infection 0/11 (0%) 1/6 (16.7%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Folliculitis 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 0/160 (0%) 1/6 (16.7%) 0/6 (0%) 1/12 (8.3%) 1/172 (0.6%)
Gastroenteritis 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 2/36 (5.6%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Herpes virus infection 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 1/20 (5%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Nasopharyngitis 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 1/7 (14.3%) 1/30 (3.3%) 2/36 (5.6%) 0/20 (0%) 5/160 (3.1%) 2/6 (33.3%) 0/6 (0%) 2/12 (16.7%) 7/172 (4.1%)
Pneumonia 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 2/30 (6.7%) 1/36 (2.8%) 0/20 (0%) 4/160 (2.5%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 4/172 (2.3%)
Rash pustular 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 1/36 (2.8%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 1/6 (16.7%) 1/12 (8.3%) 2/172 (1.2%)
Rhinitis 0/11 (0%) 0/6 (0%) 0/5 (0%) 2/26 (7.7%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 1/36 (2.8%) 1/20 (5%) 5/160 (3.1%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 5/172 (2.9%)
Sinusitis 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 0/160 (0%) 0/6 (0%) 1/6 (16.7%) 1/12 (8.3%) 1/172 (0.6%)
Tinea cruris 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 0/160 (0%) 0/6 (0%) 1/6 (16.7%) 1/12 (8.3%) 1/172 (0.6%)
Urinary tract infection 0/11 (0%) 0/6 (0%) 1/5 (20%) 2/26 (7.7%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 1/36 (2.8%) 0/20 (0%) 4/160 (2.5%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 4/172 (2.3%)
Injury, poisoning and procedural complications
Animal bite 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Bone contusion 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Procedural pain 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 5/30 (16.7%) 0/36 (0%) 1/20 (5%) 7/160 (4.4%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 7/172 (4.1%)
Investigations
Activated partial thromboplastin time prolonged 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 1/20 (5%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Alanine aminotransferase increased 3/11 (27.3%) 3/6 (50%) 2/5 (40%) 14/26 (53.8%) 11/19 (57.9%) 7/7 (100%) 13/30 (43.3%) 11/36 (30.6%) 6/20 (30%) 70/160 (43.8%) 0/6 (0%) 4/6 (66.7%) 4/12 (33.3%) 74/172 (43%)
Amylase increased 0/11 (0%) 1/6 (16.7%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 1/30 (3.3%) 2/36 (5.6%) 0/20 (0%) 4/160 (2.5%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 4/172 (2.3%)
Aspartate aminotransferase increased 4/11 (36.4%) 3/6 (50%) 2/5 (40%) 16/26 (61.5%) 14/19 (73.7%) 7/7 (100%) 14/30 (46.7%) 11/36 (30.6%) 5/20 (25%) 76/160 (47.5%) 1/6 (16.7%) 5/6 (83.3%) 6/12 (50%) 82/172 (47.7%)
Bilirubin conjugated increased 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 0/160 (0%) 1/6 (16.7%) 0/6 (0%) 1/12 (8.3%) 1/172 (0.6%)
Blood albumin decreased 0/11 (0%) 1/6 (16.7%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 1/6 (16.7%) 0/6 (0%) 1/12 (8.3%) 2/172 (1.2%)
Blood alkaline phosphatase increased 1/11 (9.1%) 0/6 (0%) 1/5 (20%) 4/26 (15.4%) 5/19 (26.3%) 1/7 (14.3%) 4/30 (13.3%) 2/36 (5.6%) 2/20 (10%) 20/160 (12.5%) 0/6 (0%) 1/6 (16.7%) 1/12 (8.3%) 21/172 (12.2%)
Blood bilirubin increased 4/11 (36.4%) 3/6 (50%) 1/5 (20%) 11/26 (42.3%) 2/19 (10.5%) 0/7 (0%) 6/30 (20%) 3/36 (8.3%) 1/20 (5%) 31/160 (19.4%) 1/6 (16.7%) 2/6 (33.3%) 3/12 (25%) 34/172 (19.8%)
Blood cholesterol increased 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Blood creatine phosphokinase increased 0/11 (0%) 1/6 (16.7%) 0/5 (0%) 1/26 (3.8%) 2/19 (10.5%) 0/7 (0%) 0/30 (0%) 1/36 (2.8%) 0/20 (0%) 5/160 (3.1%) 0/6 (0%) 1/6 (16.7%) 1/12 (8.3%) 6/172 (3.5%)
Blood creatinine increased 0/11 (0%) 0/6 (0%) 1/5 (20%) 2/26 (7.7%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 1/36 (2.8%) 0/20 (0%) 4/160 (2.5%) 0/6 (0%) 1/6 (16.7%) 1/12 (8.3%) 5/172 (2.9%)
Blood phosphorus decreased 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 0/160 (0%) 1/6 (16.7%) 0/6 (0%) 1/12 (8.3%) 1/172 (0.6%)
C-reactive protein increased 0/11 (0%) 0/6 (0%) 0/5 (0%) 2/26 (7.7%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 1/36 (2.8%) 0/20 (0%) 3/160 (1.9%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 3/172 (1.7%)
Gamma-glutamyltransferase increased 0/11 (0%) 1/6 (16.7%) 0/5 (0%) 4/26 (15.4%) 2/19 (10.5%) 0/7 (0%) 4/30 (13.3%) 3/36 (8.3%) 3/20 (15%) 17/160 (10.6%) 1/6 (16.7%) 1/6 (16.7%) 2/12 (16.7%) 19/172 (11%)
Haemoglobin decreased 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Lipase increased 0/11 (0%) 1/6 (16.7%) 1/5 (20%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 4/30 (13.3%) 6/36 (16.7%) 1/20 (5%) 14/160 (8.8%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 14/172 (8.1%)
Neutrophil count decreased 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 2/30 (6.7%) 0/36 (0%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 2/6 (33.3%) 2/12 (16.7%) 4/172 (2.3%)
Platelet count decreased 0/11 (0%) 0/6 (0%) 1/5 (20%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 2/30 (6.7%) 2/36 (5.6%) 1/20 (5%) 6/160 (3.8%) 0/6 (0%) 1/6 (16.7%) 1/12 (8.3%) 7/172 (4.1%)
Prothrombin time prolonged 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Transaminases increased 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 1/36 (2.8%) 1/20 (5%) 3/160 (1.9%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 3/172 (1.7%)
Weight decreased 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 2/19 (10.5%) 1/7 (14.3%) 0/30 (0%) 4/36 (11.1%) 4/20 (20%) 12/160 (7.5%) 0/6 (0%) 1/6 (16.7%) 1/12 (8.3%) 13/172 (7.6%)
Metabolism and nutrition disorders
Decreased appetite 3/11 (27.3%) 1/6 (16.7%) 0/5 (0%) 10/26 (38.5%) 2/19 (10.5%) 4/7 (57.1%) 6/30 (20%) 9/36 (25%) 12/20 (60%) 47/160 (29.4%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 47/172 (27.3%)
Hypercalcaemia 1/11 (9.1%) 1/6 (16.7%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 1/20 (5%) 4/160 (2.5%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 4/172 (2.3%)
Hyperglycaemia 0/11 (0%) 0/6 (0%) 1/5 (20%) 1/26 (3.8%) 1/19 (5.3%) 0/7 (0%) 1/30 (3.3%) 1/36 (2.8%) 0/20 (0%) 5/160 (3.1%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 5/172 (2.9%)
Hyperkalaemia 0/11 (0%) 0/6 (0%) 1/5 (20%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 1/36 (2.8%) 0/20 (0%) 3/160 (1.9%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 3/172 (1.7%)
Hyperlipasaemia 0/11 (0%) 1/6 (16.7%) 1/5 (20%) 2/26 (7.7%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 2/36 (5.6%) 0/20 (0%) 6/160 (3.8%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 6/172 (3.5%)
Hyperphosphataemia 0/11 (0%) 1/6 (16.7%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 1/7 (14.3%) 3/30 (10%) 1/36 (2.8%) 2/20 (10%) 8/160 (5%) 2/6 (33.3%) 3/6 (50%) 5/12 (41.7%) 13/172 (7.6%)
Hypertriglyceridaemia 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 2/26 (7.7%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 3/160 (1.9%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 3/172 (1.7%)
Hyperuricaemia 0/11 (0%) 0/6 (0%) 0/5 (0%) 2/26 (7.7%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Hypoalbuminaemia 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 3/26 (11.5%) 0/19 (0%) 0/7 (0%) 7/30 (23.3%) 1/36 (2.8%) 2/20 (10%) 14/160 (8.8%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 14/172 (8.1%)
Hypokalaemia 0/11 (0%) 0/6 (0%) 0/5 (0%) 3/26 (11.5%) 0/19 (0%) 1/7 (14.3%) 0/30 (0%) 1/36 (2.8%) 0/20 (0%) 5/160 (3.1%) 0/6 (0%) 1/6 (16.7%) 1/12 (8.3%) 6/172 (3.5%)
Hypomagnesaemia 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Hyponatraemia 0/11 (0%) 1/6 (16.7%) 1/5 (20%) 3/26 (11.5%) 2/19 (10.5%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 7/160 (4.4%) 1/6 (16.7%) 0/6 (0%) 1/12 (8.3%) 8/172 (4.7%)
Hypophosphataemia 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 1/30 (3.3%) 0/36 (0%) 1/20 (5%) 3/160 (1.9%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 3/172 (1.7%)
Malnutrition 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 1/7 (14.3%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Musculoskeletal and connective tissue disorders
Arthralgia 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 2/36 (5.6%) 1/20 (5%) 3/160 (1.9%) 1/6 (16.7%) 1/6 (16.7%) 2/12 (16.7%) 5/172 (2.9%)
Back pain 0/11 (0%) 1/6 (16.7%) 0/5 (0%) 2/26 (7.7%) 0/19 (0%) 1/7 (14.3%) 5/30 (16.7%) 4/36 (11.1%) 1/20 (5%) 14/160 (8.8%) 2/6 (33.3%) 0/6 (0%) 2/12 (16.7%) 16/172 (9.3%)
Flank pain 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 2/30 (6.7%) 0/36 (0%) 0/20 (0%) 3/160 (1.9%) 1/6 (16.7%) 0/6 (0%) 1/12 (8.3%) 4/172 (2.3%)
Groin pain 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Muscle spasms 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 2/36 (5.6%) 1/20 (5%) 3/160 (1.9%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 3/172 (1.7%)
Musculoskeletal chest pain 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 1/7 (14.3%) 1/30 (3.3%) 0/36 (0%) 1/20 (5%) 3/160 (1.9%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 3/172 (1.7%)
Musculoskeletal pain 0/11 (0%) 0/6 (0%) 0/5 (0%) 3/26 (11.5%) 1/19 (5.3%) 0/7 (0%) 3/30 (10%) 2/36 (5.6%) 3/20 (15%) 12/160 (7.5%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 12/172 (7%)
Myalgia 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 3/30 (10%) 0/36 (0%) 1/20 (5%) 4/160 (2.5%) 0/6 (0%) 1/6 (16.7%) 1/12 (8.3%) 5/172 (2.9%)
Osteoporosis 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 2/36 (5.6%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Pain in extremity 0/11 (0%) 1/6 (16.7%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 2/30 (6.7%) 0/36 (0%) 0/20 (0%) 3/160 (1.9%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 3/172 (1.7%)
Spinal pain 0/11 (0%) 1/6 (16.7%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Tumour associated fever 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 1/7 (14.3%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Nervous system disorders
Dizziness 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 2/30 (6.7%) 0/36 (0%) 0/20 (0%) 3/160 (1.9%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 3/172 (1.7%)
Dysgeusia 3/11 (27.3%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 1/30 (3.3%) 1/36 (2.8%) 1/20 (5%) 6/160 (3.8%) 0/6 (0%) 1/6 (16.7%) 1/12 (8.3%) 7/172 (4.1%)
Headache 1/11 (9.1%) 0/6 (0%) 1/5 (20%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 4/30 (13.3%) 3/36 (8.3%) 3/20 (15%) 12/160 (7.5%) 0/6 (0%) 1/6 (16.7%) 1/12 (8.3%) 13/172 (7.6%)
Peripheral sensory neuropathy 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 0/160 (0%) 1/6 (16.7%) 0/6 (0%) 1/12 (8.3%) 1/172 (0.6%)
Spinal cord compression 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Visual field defect 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Psychiatric disorders
Anxiety 0/11 (0%) 1/6 (16.7%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 1/30 (3.3%) 2/36 (5.6%) 1/20 (5%) 5/160 (3.1%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 5/172 (2.9%)
Depression 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 1/36 (2.8%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Insomnia 0/11 (0%) 0/6 (0%) 1/5 (20%) 1/26 (3.8%) 1/19 (5.3%) 2/7 (28.6%) 4/30 (13.3%) 2/36 (5.6%) 5/20 (25%) 16/160 (10%) 0/6 (0%) 1/6 (16.7%) 1/12 (8.3%) 17/172 (9.9%)
Sleep disorder 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 2/36 (5.6%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Reproductive system and breast disorders
Female genital tract fistula 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Scrotal oedema 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 1/7 (14.3%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Varicocele 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Respiratory, thoracic and mediastinal disorders
Bronchostenosis 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Cough 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 2/26 (7.7%) 2/19 (10.5%) 2/7 (28.6%) 7/30 (23.3%) 3/36 (8.3%) 2/20 (10%) 19/160 (11.9%) 0/6 (0%) 1/6 (16.7%) 1/12 (8.3%) 20/172 (11.6%)
Dysphonia 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 1/36 (2.8%) 1/20 (5%) 2/160 (1.3%) 1/6 (16.7%) 0/6 (0%) 1/12 (8.3%) 3/172 (1.7%)
Dyspnoea 1/11 (9.1%) 1/6 (16.7%) 1/5 (20%) 3/26 (11.5%) 0/19 (0%) 1/7 (14.3%) 4/30 (13.3%) 3/36 (8.3%) 3/20 (15%) 17/160 (10.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 17/172 (9.9%)
Dyspnoea exertional 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 1/36 (2.8%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 1/6 (16.7%) 1/12 (8.3%) 2/172 (1.2%)
Epistaxis 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 1/30 (3.3%) 0/36 (0%) 1/20 (5%) 2/160 (1.3%) 0/6 (0%) 1/6 (16.7%) 1/12 (8.3%) 3/172 (1.7%)
Haemoptysis 0/11 (0%) 0/6 (0%) 1/5 (20%) 0/26 (0%) 0/19 (0%) 1/7 (14.3%) 3/30 (10%) 0/36 (0%) 0/20 (0%) 5/160 (3.1%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 5/172 (2.9%)
Oropharyngeal pain 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 1/7 (14.3%) 2/30 (6.7%) 1/36 (2.8%) 0/20 (0%) 4/160 (2.5%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 4/172 (2.3%)
Pleural effusion 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 2/20 (10%) 3/160 (1.9%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 3/172 (1.7%)
Pneumonitis 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 1/6 (16.7%) 1/12 (8.3%) 2/172 (1.2%)
Productive cough 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 3/30 (10%) 1/36 (2.8%) 0/20 (0%) 6/160 (3.8%) 0/6 (0%) 1/6 (16.7%) 1/12 (8.3%) 7/172 (4.1%)
Skin and subcutaneous tissue disorders
Dry skin 0/11 (0%) 0/6 (0%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 4/36 (11.1%) 2/20 (10%) 7/160 (4.4%) 1/6 (16.7%) 0/6 (0%) 1/12 (8.3%) 8/172 (4.7%)
Night sweats 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 3/36 (8.3%) 0/20 (0%) 3/160 (1.9%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 3/172 (1.7%)
Pruritus 2/11 (18.2%) 2/6 (33.3%) 1/5 (20%) 4/26 (15.4%) 5/19 (26.3%) 1/7 (14.3%) 5/30 (16.7%) 8/36 (22.2%) 0/20 (0%) 28/160 (17.5%) 0/6 (0%) 2/6 (33.3%) 2/12 (16.7%) 30/172 (17.4%)
Rash 1/11 (9.1%) 1/6 (16.7%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 1/7 (14.3%) 1/30 (3.3%) 0/36 (0%) 2/20 (10%) 6/160 (3.8%) 0/6 (0%) 2/6 (33.3%) 2/12 (16.7%) 8/172 (4.7%)
Rash macular 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Rash maculo-papular 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 1/19 (5.3%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)
Vascular disorders
Haematoma 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 2/36 (5.6%) 0/20 (0%) 2/160 (1.3%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 2/172 (1.2%)
Hot flush 0/11 (0%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 0/160 (0%) 1/6 (16.7%) 1/6 (16.7%) 2/12 (16.7%) 2/172 (1.2%)
Hypertension 0/11 (0%) 1/6 (16.7%) 0/5 (0%) 1/26 (3.8%) 0/19 (0%) 2/7 (28.6%) 0/30 (0%) 3/36 (8.3%) 2/20 (10%) 9/160 (5.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 9/172 (5.2%)
Vena cava thrombosis 1/11 (9.1%) 0/6 (0%) 0/5 (0%) 0/26 (0%) 0/19 (0%) 0/7 (0%) 0/30 (0%) 0/36 (0%) 0/20 (0%) 1/160 (0.6%) 0/6 (0%) 0/6 (0%) 0/12 (0%) 1/172 (0.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.

Results Point of Contact

Name/Title Study Director
Organization Novartis Pharmaceuticals
Phone 862-778-8300
Email novartis.email@novartis.com
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02325739
Other Study ID Numbers:
  • CFGF401X2101
  • 2014-002929-35
First Posted:
Dec 25, 2014
Last Update Posted:
Dec 17, 2020
Last Verified:
Nov 1, 2020