Hepatocellular Carcinoma (HCC), Solid Malignancies
Conditions
Keywords
FGF401, PDR001, PD-1, FGFR4, FGF19, HCC, solid malignancies characterized by positive FGFR4 and KLB expression
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.
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.
Interventions
DRUGFGF401
FGF401 is a FGFR4 inhibitor.
BIOLOGICALPDR001
PDR001 is a humanized anti-PD1 IgG4 antibody that blocks the binding of PD-L1 and PD-L2
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 4. Pregnant or nursing (lactating) women. Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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) |
| 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) |
| 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. |
| 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) |
| 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) |
| 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) |
| 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) |
| 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). |
| 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. |
| 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) |
| 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). |
Countries
China, France, Germany, Hong Kong, Italy, Japan, Singapore, South Korea, Spain, Taiwan, United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Phase I: 50 mg Fasted Participants received single agent FGF401 50 mg while fasted | 11 |
| Phase I: 80 mg Fasted Participants received single agent FGF401 80 mg while fasted | 6 |
| Phase I: 80 mg Fed Participants received single agent FGF401 80 mg while fed | 5 |
| Phase I: 120 mg Fasted Participants received single agent FGF401 120 mg while fasted | 26 |
| Phase I: 120 mg Fed Participants received single agent FGF401 120 mg while fed | 19 |
| Phase I: 150 mg Fasted Participants received single agent FGF401 150 mg while fasted | 7 |
| Phase I: FGF401 80 mg + PDR001 300 mg Participants received FGF401 80 mg in combination with PDR001 300 mg while fasted | 6 |
| Phase I: FGF401 120 mg + PDR001 300 mg Participants received FGF401 120 mg in combination with PDR001 300 mg while fasted | 6 |
| Phase II: Group 1 - FGF401 120 mg QD Group 1 was comprised of HCC participants from Asian contrives who took single agent FGF401 120 mg QD while fasted | 30 |
| 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 | 36 |
| PhaseII: 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 | 20 |
| Total | 172 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Phase II Part | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 5 | 1 |
| Phase II Part | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Phase II Part | Progressive disease | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 22 | 29 | 18 |
| Phase II Part | Subject/guardian decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 1 | 1 |
| Phase I Part | Adverse Event | 1 | 0 | 1 | 2 | 3 | 1 | 0 | 2 | 0 | 0 | 0 |
| Phase I Part | Death | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Phase I Part | Progressive disease | 9 | 6 | 3 | 23 | 14 | 6 | 6 | 3 | 0 | 0 | 0 |
| Phase I Part | Subject/guardian decision | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | 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 I: 50 mg Fasted | Phase II: Group 2 - FGF401 120 mg QD | PhaseII: Group 3 - FGF401 120 mg QD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18 y - <65 y | 96 participants | 4 participants | 3 participants | 14 participants | 12 participants | 4 participants | 3 participants | 3 participants | 22 participants | 6 participants | 15 participants | 10 participants |
| Age, Customized 65 y - <85 y | 75 participants | 2 participants | 2 participants | 12 participants | 6 participants | 3 participants | 3 participants | 3 participants | 8 participants | 5 participants | 21 participants | 10 participants |
| Age, Customized >=85 y | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 81 participants | 2 participants | 2 participants | 14 participants | 10 participants | 4 participants | 3 participants | 5 participants | 30 participants | 9 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Black | 2 participants | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Caucasian | 66 participants | 4 participants | 3 participants | 12 participants | 8 participants | 1 participants | 3 participants | 1 participants | 0 participants | 2 participants | 21 participants | 11 participants |
| Race/Ethnicity, Customized Not applicable | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Other | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Pacific Islander | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Unknown | 20 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 12 participants | 7 participants |
| Sex: Female, Male Female | 47 Participants | 1 Participants | 1 Participants | 3 Participants | 6 Participants | 0 Participants | 1 Participants | 4 Participants | 8 Participants | 4 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Male | 125 Participants | 5 Participants | 4 Participants | 23 Participants | 13 Participants | 7 Participants | 5 Participants | 2 Participants | 22 Participants | 7 Participants | 29 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 11 | 1 / 6 | 0 / 5 | 4 / 26 | 6 / 19 | 1 / 7 | 2 / 30 | 2 / 36 | 2 / 20 | 20 / 160 | 0 / 6 | 0 / 6 | 0 / 12 | 20 / 172 |
| other Total, other adverse events | 11 / 11 | 6 / 6 | 5 / 5 | 26 / 26 | 19 / 19 | 7 / 7 | 29 / 30 | 36 / 36 | 20 / 20 | 159 / 160 | 6 / 6 | 6 / 6 | 12 / 12 | 171 / 172 |
| serious Total, serious adverse events | 3 / 11 | 5 / 6 | 3 / 5 | 15 / 26 | 9 / 19 | 3 / 7 | 15 / 30 | 9 / 36 | 8 / 20 | 70 / 160 | 0 / 6 | 2 / 6 | 2 / 12 | 72 / 172 |
Outcome results
Primary
Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only
A dose-limiting toxicity was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the evaluation period of DLTs and met any of the criteria listed. The estimation of the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of the treatment was based upon the estimation of the probability of DLT during the evaluation period for subjects in the dose determining set (DDS). A subject with multiple occurrences of a DLT under one treatment is counted only once in the AE category for that treatment. A subject with multiple DLTs within a primary system organ class is counted only once in the total row.
Time frame: Cycle 1 (C1) (21 days) for FGF401 single agent, Cycle 1 and Cycle 2 (C2) (42 days) for FGF401 and PDR001 combination
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I: 50 mg Fasted | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Invest.: Aspartate Aminotrans. increased | 0 Percentage of participants |
| Phase I: 50 mg Fasted | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Invest.: Blood bilirubin increased | 0 Percentage of participants |
| Phase I: 50 mg Fasted | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Any Primary system organ class (SOC) | 10.0 Percentage of participants |
| Phase I: 50 mg Fasted | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Invest.: Alanine aminotrans. increased | 10.0 Percentage of participants |
| Phase I: 80 mg Fasted | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Invest.: Blood bilirubin increased | 0 Percentage of participants |
| Phase I: 80 mg Fasted | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Any Primary system organ class (SOC) | 0 Percentage of participants |
| Phase I: 80 mg Fasted | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Invest.: Aspartate Aminotrans. increased | 0 Percentage of participants |
| Phase I: 80 mg Fasted | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Invest.: Alanine aminotrans. increased | 0 Percentage of participants |
| Phase I: 80 mg Fed | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Invest.: Aspartate Aminotrans. increased | 0 Percentage of participants |
| Phase I: 80 mg Fed | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Any Primary system organ class (SOC) | 0 Percentage of participants |
| Phase I: 80 mg Fed | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Invest.: Alanine aminotrans. increased | 0 Percentage of participants |
| Phase I: 80 mg Fed | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Invest.: Blood bilirubin increased | 0 Percentage of participants |
| Phase I: 120 mg Fasted | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Invest.: Alanine aminotrans. increased | 0 Percentage of participants |
| Phase I: 120 mg Fasted | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Invest.: Aspartate Aminotrans. increased | 4.3 Percentage of participants |
| Phase I: 120 mg Fasted | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Invest.: Blood bilirubin increased | 0 Percentage of participants |
| Phase I: 120 mg Fasted | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Any Primary system organ class (SOC) | 4.3 Percentage of participants |
| Phase I: 120 mg Fed | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Invest.: Aspartate Aminotrans. increased | 0 Percentage of participants |
| Phase I: 120 mg Fed | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Invest.: Alanine aminotrans. increased | 0 Percentage of participants |
| Phase I: 120 mg Fed | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Any Primary system organ class (SOC) | 5.6 Percentage of participants |
| Phase I: 120 mg Fed | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Invest.: Blood bilirubin increased | 5.6 Percentage of participants |
| Phase I: 150 mg Fasted | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Any Primary system organ class (SOC) | 42.9 Percentage of participants |
| Phase I: 150 mg Fasted | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Invest.: Aspartate Aminotrans. increased | 42.9 Percentage of participants |
| Phase I: 150 mg Fasted | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Invest.: Alanine aminotrans. increased | 14.3 Percentage of participants |
| Phase I: 150 mg Fasted | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Invest.: Blood bilirubin increased | 0 Percentage of participants |
| Phase I: FGF401 80 mg + PDR001 300 mg | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Any Primary system organ class (SOC) | 0 Percentage of participants |
| Phase I: FGF401 80 mg + PDR001 300 mg | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Invest.: Alanine aminotrans. increased | 0 Percentage of participants |
| Phase I: FGF401 80 mg + PDR001 300 mg | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Invest.: Aspartate Aminotrans. increased | 0 Percentage of participants |
| Phase I: FGF401 80 mg + PDR001 300 mg | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Invest.: Blood bilirubin increased | 0 Percentage of participants |
| Phase I: FGF401 120 mg + PDR001 300 mg | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Invest.: Aspartate Aminotrans. increased | 0 Percentage of participants |
| Phase I: FGF401 120 mg + PDR001 300 mg | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Any Primary system organ class (SOC) | 0 Percentage of participants |
| Phase I: FGF401 120 mg + PDR001 300 mg | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Invest.: Blood bilirubin increased | 0 Percentage of participants |
| Phase I: FGF401 120 mg + PDR001 300 mg | Number of Participants With Dose-limiting Toxicity (DLT): Phase I Only | Invest.: Alanine aminotrans. increased | 0 Percentage of participants |
Primary
Overall Response Rate (ORR) Based on Local Assessment: Group 3 (Phase II Only)
ORR is defined as the percentage of patients with a best overall response of CR or PR (RECIST v1.1). FGF401 single agent-Phase II part - Group 3 (non-HCC, other solid tumors).
Time frame: approx. 4.5 years
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Phase I: 50 mg Fasted | Overall Response Rate (ORR) Based on Local Assessment: Group 3 (Phase II Only) | 0 Percentage of participants |
Primary
Time to Progression (TTP): Group 1 & Group 2 (Phase II Only)
TTP is defined as the date of start treatment to the date of event defined as the first documented progression or death due to underlying cancer. Method used was Kaplan-Meier analysis. Group 1: HCC subjects form Asian countries; Group 2: HCC subjects form non-Asian countries
Time frame: approx. 4.5 years
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I: 50 mg Fasted | Time to Progression (TTP): Group 1 & Group 2 (Phase II Only) | 2.6 months |
| Phase I: 80 mg Fasted | Time to Progression (TTP): Group 1 & Group 2 (Phase II Only) | 3.9 months |
Secondary
AUCinf, AUClast & AUCtau of FGF401 in Combination With PDR001: Phase I
AUCinf: The AUC from time zero to infinity (mass x time x volume-1) AUClast: The AUC from time zero to the last measurable concentration sampling time (Tlast) (mass x time x volume-1) AUCtau: The AUC calculated to the end of a dosing interval (tau) (amount x time x volume-1)
Time frame: C1D1 (0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 12h, 24h)
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: 50 mg Fasted | AUCinf, AUClast & AUCtau of FGF401 in Combination With PDR001: Phase I | AUCinf | 5030 hr*ng/mL | Geometric Coefficient of Variation 25.5 |
| Phase I: 50 mg Fasted | AUCinf, AUClast & AUCtau of FGF401 in Combination With PDR001: Phase I | AUClast | 4760 hr*ng/mL | Geometric Coefficient of Variation 25 |
| Phase I: 50 mg Fasted | AUCinf, AUClast & AUCtau of FGF401 in Combination With PDR001: Phase I | AUCtau | 4770 hr*ng/mL | Geometric Coefficient of Variation 24.4 |
| Phase I: 80 mg Fasted | AUCinf, AUClast & AUCtau of FGF401 in Combination With PDR001: Phase I | AUCinf | 7540 hr*ng/mL | Geometric Coefficient of Variation 37 |
| Phase I: 80 mg Fasted | AUCinf, AUClast & AUCtau of FGF401 in Combination With PDR001: Phase I | AUClast | 7280 hr*ng/mL | Geometric Coefficient of Variation 36.7 |
| Phase I: 80 mg Fasted | AUCinf, AUClast & AUCtau of FGF401 in Combination With PDR001: Phase I | AUCtau | 7280 hr*ng/mL | Geometric Coefficient of Variation 36.7 |
Secondary
AUCinf, AUClast & AUCtau of FGF401: Phase I
AUCinf: The AUC from time zero to infinity (mass x time x volume-1) AUClast: The AUC from time zero to the last measurable concentration sampling time (Tlast) (mass x time x volume-1) AUCtau: The AUC calculated to the end of a dosing interval (tau) (amount x time x volume-1)
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)
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: 50 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUClast C2D1 | 4100 hr*ng/mL | Geometric Coefficient of Variation 52.9 |
| Phase I: 50 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCtau C2D1 | 4100 hr*ng/mL | Geometric Coefficient of Variation 52.7 |
| Phase I: 50 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCtau C1D1 | 4610 hr*ng/mL | Geometric Coefficient of Variation 50.4 |
| Phase I: 50 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCtau C1D8 | 3650 hr*ng/mL | Geometric Coefficient of Variation 65.6 |
| Phase I: 50 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCinf C2D1 | 4390 hr*ng/mL | Geometric Coefficient of Variation 54 |
| Phase I: 50 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUClast C1D8 | 3460 hr*ng/mL | Geometric Coefficient of Variation 62.5 |
| Phase I: 50 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUClast C1D1 | 4610 hr*ng/mL | Geometric Coefficient of Variation 50.4 |
| Phase I: 50 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCinf C1D1 | 4920 hr*ng/mL | Geometric Coefficient of Variation 51.9 |
| Phase I: 50 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCinf C1D8 | 3650 hr*ng/mL | Geometric Coefficient of Variation 71.9 |
| Phase I: 80 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCtau C2D1 | 4360 hr*ng/mL | Geometric Coefficient of Variation 28.5 |
| Phase I: 80 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCtau C1D8 | 4850 hr*ng/mL | Geometric Coefficient of Variation 27 |
| Phase I: 80 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUClast C1D1 | 4710 hr*ng/mL | Geometric Coefficient of Variation 38 |
| Phase I: 80 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCtau C1D1 | 4910 hr*ng/mL | Geometric Coefficient of Variation 30.3 |
| Phase I: 80 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCinf C1D1 | 5090 hr*ng/mL | Geometric Coefficient of Variation 32.9 |
| Phase I: 80 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUClast C2D1 | 4210 hr*ng/mL | Geometric Coefficient of Variation 32.5 |
| Phase I: 80 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCinf C1D8 | 5130 hr*ng/mL | Geometric Coefficient of Variation 28.9 |
| Phase I: 80 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCinf C2D1 | 4580 hr*ng/mL | Geometric Coefficient of Variation 30.6 |
| Phase I: 80 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUClast C1D8 | 4840 hr*ng/mL | Geometric Coefficient of Variation 27 |
| Phase I: 80 mg Fed | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUClast C1D1 | 4600 hr*ng/mL | Geometric Coefficient of Variation 39.2 |
| Phase I: 80 mg Fed | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCtau C1D8 | 5290 hr*ng/mL | Geometric Coefficient of Variation 24 |
| Phase I: 80 mg Fed | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCinf C1D8 | 5550 hr*ng/mL | Geometric Coefficient of Variation 23.2 |
| Phase I: 80 mg Fed | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUClast C2D1 | 4880 hr*ng/mL | Geometric Coefficient of Variation 43.1 |
| Phase I: 80 mg Fed | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCtau C2D1 | 4870 hr*ng/mL | Geometric Coefficient of Variation 43.7 |
| Phase I: 80 mg Fed | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCtau C1D1 | 4860 hr*ng/mL | Geometric Coefficient of Variation 29.4 |
| Phase I: 80 mg Fed | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCinf C2D1 | 5110 hr*ng/mL | Geometric Coefficient of Variation 44.3 |
| Phase I: 80 mg Fed | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUClast C1D8 | 5280 hr*ng/mL | Geometric Coefficient of Variation 23.9 |
| Phase I: 80 mg Fed | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCinf C1D1 | 5560 hr*ng/mL | Geometric Coefficient of Variation 23.1 |
| Phase I: 120 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCtau C1D8 | 6970 hr*ng/mL | Geometric Coefficient of Variation 38.7 |
| Phase I: 120 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCinf C1D1 | 7210 hr*ng/mL | Geometric Coefficient of Variation 35.4 |
| Phase I: 120 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUClast C1D1 | 6710 hr*ng/mL | Geometric Coefficient of Variation 35.6 |
| Phase I: 120 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCtau C1D1 | 6840 hr*ng/mL | Geometric Coefficient of Variation 33.6 |
| Phase I: 120 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCinf C1D8 | 7590 hr*ng/mL | Geometric Coefficient of Variation 43 |
| Phase I: 120 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUClast C1D8 | 6480 hr*ng/mL | Geometric Coefficient of Variation 47.5 |
| Phase I: 120 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCinf C2D1 | 7770 hr*ng/mL | Geometric Coefficient of Variation 33.2 |
| Phase I: 120 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUClast C2D1 | 7260 hr*ng/mL | Geometric Coefficient of Variation 33.6 |
| Phase I: 120 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCtau C2D1 | 7330 hr*ng/mL | Geometric Coefficient of Variation 31.7 |
| Phase I: 120 mg Fed | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUClast C1D8 | 7640 hr*ng/mL | Geometric Coefficient of Variation 33.1 |
| Phase I: 120 mg Fed | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCinf C1D8 | 7980 hr*ng/mL | Geometric Coefficient of Variation 25.1 |
| Phase I: 120 mg Fed | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCinf C2D1 | 8760 hr*ng/mL | Geometric Coefficient of Variation 23.5 |
| Phase I: 120 mg Fed | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCtau C1D1 | 8020 hr*ng/mL | Geometric Coefficient of Variation 33.5 |
| Phase I: 120 mg Fed | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCtau C2D1 | 7830 hr*ng/mL | Geometric Coefficient of Variation 23.4 |
| Phase I: 120 mg Fed | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUClast C2D1 | 7520 hr*ng/mL | Geometric Coefficient of Variation 38.7 |
| Phase I: 120 mg Fed | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUClast C1D1 | 7850 hr*ng/mL | Geometric Coefficient of Variation 34.1 |
| Phase I: 120 mg Fed | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCinf C1D1 | 8520 hr*ng/mL | Geometric Coefficient of Variation 35.2 |
| Phase I: 120 mg Fed | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCtau C1D8 | 7330 hr*ng/mL | Geometric Coefficient of Variation 26.7 |
| Phase I: 150 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCinf C1D1 | 8190 hr*ng/mL | Geometric Coefficient of Variation 42.7 |
| Phase I: 150 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCinf C1D8 | 7850 hr*ng/mL | Geometric Coefficient of Variation 29.4 |
| Phase I: 150 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCtau C1D8 | 7510 hr*ng/mL | Geometric Coefficient of Variation 29.8 |
| Phase I: 150 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCtau C2D1 | 7620 hr*ng/mL | Geometric Coefficient of Variation 25.7 |
| Phase I: 150 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUClast C2D1 | 7610 hr*ng/mL | Geometric Coefficient of Variation 25.8 |
| Phase I: 150 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCinf C2D1 | 7850 hr*ng/mL | Geometric Coefficient of Variation 25.7 |
| Phase I: 150 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUCtau C1D1 | 7930 hr*ng/mL | Geometric Coefficient of Variation 41.8 |
| Phase I: 150 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUClast C1D8 | 7550 hr*ng/mL | Geometric Coefficient of Variation 28.6 |
| Phase I: 150 mg Fasted | AUCinf, AUClast & AUCtau of FGF401: Phase I | AUClast C1D1 | 7920 hr*ng/mL | Geometric Coefficient of Variation 42 |
Secondary
AUClast and AUCtau of PDR001 in Combination of FGF401: Phase I
AUClast: The AUC from time zero to the last measurable concentration sampling time (Tlast) (mass x time x volume-1) AUCtau (AUC0 504h): The AUC calculated to the end of a dosing interval (tau) (amount x time x volume-1)
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: 50 mg Fasted | AUClast and AUCtau of PDR001 in Combination of FGF401: Phase I | AUClast | 795 day*μg/mL | Geometric Coefficient of Variation 34.5 |
| Phase I: 50 mg Fasted | AUClast and AUCtau of PDR001 in Combination of FGF401: Phase I | AUC0-504h (n = 3, 6) | 760 day*μg/mL | Geometric Coefficient of Variation 1.9 |
| Phase I: 80 mg Fasted | AUClast and AUCtau of PDR001 in Combination of FGF401: Phase I | AUClast | 978 day*μg/mL | Geometric Coefficient of Variation 15.8 |
| Phase I: 80 mg Fasted | AUClast and AUCtau of PDR001 in Combination of FGF401: Phase I | AUC0-504h (n = 3, 6) | 967 day*μg/mL | Geometric Coefficient of Variation 13.9 |
Secondary
Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II
BOR is the best response recorded from the start of the treatment until disease progression/recurrence. BOR is determined according to: complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) and unknown.
Time frame: approx. 4.5 years
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase I: 50 mg Fasted | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Stable Disease | 2 Participants |
| Phase I: 50 mg Fasted | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Unknown | 2 Participants |
| Phase I: 50 mg Fasted | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Progressive Disease | 7 Participants |
| Phase I: 50 mg Fasted | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Partial Response | 0 Participants |
| Phase I: 50 mg Fasted | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Complete Response | 0 Participants |
| Phase I: 80 mg Fasted | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Complete Response | 0 Participants |
| Phase I: 80 mg Fasted | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Progressive Disease | 4 Participants |
| Phase I: 80 mg Fasted | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Stable Disease | 1 Participants |
| Phase I: 80 mg Fasted | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Unknown | 0 Participants |
| Phase I: 80 mg Fasted | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Partial Response | 1 Participants |
| Phase I: 80 mg Fed | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Stable Disease | 2 Participants |
| Phase I: 80 mg Fed | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Complete Response | 0 Participants |
| Phase I: 80 mg Fed | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Unknown | 1 Participants |
| Phase I: 80 mg Fed | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Partial Response | 1 Participants |
| Phase I: 80 mg Fed | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Progressive Disease | 1 Participants |
| Phase I: 120 mg Fasted | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Complete Response | 1 Participants |
| Phase I: 120 mg Fasted | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Partial Response | 0 Participants |
| Phase I: 120 mg Fasted | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Progressive Disease | 11 Participants |
| Phase I: 120 mg Fasted | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Stable Disease | 12 Participants |
| Phase I: 120 mg Fasted | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Unknown | 2 Participants |
| Phase I: 120 mg Fed | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Progressive Disease | 8 Participants |
| Phase I: 120 mg Fed | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Stable Disease | 9 Participants |
| Phase I: 120 mg Fed | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Partial Response | 0 Participants |
| Phase I: 120 mg Fed | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Unknown | 2 Participants |
| Phase I: 120 mg Fed | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Complete Response | 0 Participants |
| Phase I: 150 mg Fasted | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Progressive Disease | 2 Participants |
| Phase I: 150 mg Fasted | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Complete Response | 0 Participants |
| Phase I: 150 mg Fasted | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Partial Response | 1 Participants |
| Phase I: 150 mg Fasted | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Unknown | 0 Participants |
| Phase I: 150 mg Fasted | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Stable Disease | 4 Participants |
| Phase I: FGF401 80 mg + PDR001 300 mg | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Stable Disease | 2 Participants |
| Phase I: FGF401 80 mg + PDR001 300 mg | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Partial Response | 1 Participants |
| Phase I: FGF401 80 mg + PDR001 300 mg | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Unknown | 0 Participants |
| Phase I: FGF401 80 mg + PDR001 300 mg | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Complete Response | 0 Participants |
| Phase I: FGF401 80 mg + PDR001 300 mg | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Progressive Disease | 3 Participants |
| Phase I: FGF401 120 mg + PDR001 300 mg | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Unknown | 2 Participants |
| Phase I: FGF401 120 mg + PDR001 300 mg | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Stable Disease | 2 Participants |
| Phase I: FGF401 120 mg + PDR001 300 mg | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Partial Response | 1 Participants |
| Phase I: FGF401 120 mg + PDR001 300 mg | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Complete Response | 0 Participants |
| Phase I: FGF401 120 mg + PDR001 300 mg | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Progressive Disease | 1 Participants |
| Phase II: Group 1 - FGF401 120 mg QD | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Partial Response | 2 Participants |
| Phase II: Group 1 - FGF401 120 mg QD | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Complete Response | 0 Participants |
| Phase II: Group 1 - FGF401 120 mg QD | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Stable Disease | 11 Participants |
| Phase II: Group 1 - FGF401 120 mg QD | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Progressive Disease | 16 Participants |
| Phase II: Group 1 - FGF401 120 mg QD | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Unknown | 1 Participants |
| Phase II: Group 2 - FGF401 120 mg QD | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Partial Response | 2 Participants |
| Phase II: Group 2 - FGF401 120 mg QD | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Complete Response | 0 Participants |
| Phase II: Group 2 - FGF401 120 mg QD | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Stable Disease | 20 Participants |
| Phase II: Group 2 - FGF401 120 mg QD | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Unknown | 8 Participants |
| Phase II: Group 2 - FGF401 120 mg QD | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Progressive Disease | 6 Participants |
| PhaseII: Group 3 - FGF401 120 mg QD | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Complete Response | 0 Participants |
| PhaseII: Group 3 - FGF401 120 mg QD | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Partial Response | 0 Participants |
| PhaseII: Group 3 - FGF401 120 mg QD | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Progressive Disease | 12 Participants |
| PhaseII: Group 3 - FGF401 120 mg QD | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Stable Disease | 6 Participants |
| PhaseII: Group 3 - FGF401 120 mg QD | Best Overall Response (BOR) by Investigator Assessment: Phase I and Phase II | Unknown | 2 Participants |
Secondary
Cmax of FGF401 in Combination With PDR001: Phase I
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)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase I: 50 mg Fasted | Cmax of FGF401 in Combination With PDR001: Phase I | 732 ng/mL | Geometric Coefficient of Variation 26.8 |
| Phase I: 80 mg Fasted | Cmax of FGF401 in Combination With PDR001: Phase I | 1450 ng/mL | Geometric Coefficient of Variation 31.4 |
Secondary
Cmax of FGF401: Phase I
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)
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: 50 mg Fasted | Cmax of FGF401: Phase I | Cycle 1 Day 8 | 663 ng/mL | Geometric Coefficient of Variation 46.8 |
| Phase I: 50 mg Fasted | Cmax of FGF401: Phase I | Cycle 1 Day 1 | 698 ng/mL | Geometric Coefficient of Variation 36.1 |
| Phase I: 50 mg Fasted | Cmax of FGF401: Phase I | Cycle 2 Day 1 | 696 ng/mL | Geometric Coefficient of Variation 44.2 |
| Phase I: 80 mg Fasted | Cmax of FGF401: Phase I | Cycle 1 Day 8 | 838 ng/mL | Geometric Coefficient of Variation 16.5 |
| Phase I: 80 mg Fasted | Cmax of FGF401: Phase I | Cycle 1 Day 1 | 967 ng/mL | Geometric Coefficient of Variation 25 |
| Phase I: 80 mg Fasted | Cmax of FGF401: Phase I | Cycle 2 Day 1 | 786 ng/mL | Geometric Coefficient of Variation 25.5 |
| Phase I: 80 mg Fed | Cmax of FGF401: Phase I | Cycle 1 Day 8 | 704 ng/mL | Geometric Coefficient of Variation 22.1 |
| Phase I: 80 mg Fed | Cmax of FGF401: Phase I | Cycle 1 Day 1 | 659 ng/mL | Geometric Coefficient of Variation 15.2 |
| Phase I: 80 mg Fed | Cmax of FGF401: Phase I | Cycle 2 Day 1 | 703 ng/mL | Geometric Coefficient of Variation 41.7 |
| Phase I: 120 mg Fasted | Cmax of FGF401: Phase I | Cycle 1 Day 8 | 1120 ng/mL | Geometric Coefficient of Variation 36.5 |
| Phase I: 120 mg Fasted | Cmax of FGF401: Phase I | Cycle 1 Day 1 | 1090 ng/mL | Geometric Coefficient of Variation 37.9 |
| Phase I: 120 mg Fasted | Cmax of FGF401: Phase I | Cycle 2 Day 1 | 1070 ng/mL | Geometric Coefficient of Variation 32.2 |
| Phase I: 120 mg Fed | Cmax of FGF401: Phase I | Cycle 1 Day 8 | 1060 ng/mL | Geometric Coefficient of Variation 22.1 |
| Phase I: 120 mg Fed | Cmax of FGF401: Phase I | Cycle 1 Day 1 | 1050 ng/mL | Geometric Coefficient of Variation 32.3 |
| Phase I: 120 mg Fed | Cmax of FGF401: Phase I | Cycle 2 Day 1 | 1000 ng/mL | Geometric Coefficient of Variation 23.9 |
| Phase I: 150 mg Fasted | Cmax of FGF401: Phase I | Cycle 1 Day 1 | 1400 ng/mL | Geometric Coefficient of Variation 32.1 |
| Phase I: 150 mg Fasted | Cmax of FGF401: Phase I | Cycle 2 Day 1 | 1350 ng/mL | Geometric Coefficient of Variation 28.1 |
| Phase I: 150 mg Fasted | Cmax of FGF401: Phase I | Cycle 1 Day 8 | 1070 ng/mL | Geometric Coefficient of Variation 46 |
Secondary
Cmax of PDR001 in Combination With FGF401: Phase I
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase I: 50 mg Fasted | Cmax of PDR001 in Combination With FGF401: Phase I | 74.7 μg/mL | Geometric Coefficient of Variation 43 |
| Phase I: 80 mg Fasted | Cmax of PDR001 in Combination With FGF401: Phase I | 87.7 μg/mL | Geometric Coefficient of Variation 5.4 |
Secondary
Disease Control Rate (DCR) by Local Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1, 2 & 3
DCR is the percentage of participants with a best overall response of CR or PR or SD per local assessment according to RECIST v1.1. Phase I part and FGF401 single agent Phase II Group 1 (HCC, Asians) and Group 2 (HCC, non-Asians) and Group 3 (non-HCC, other solid tumors).
Time frame: approx. 4.5 years
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Phase I: 50 mg Fasted | Disease Control Rate (DCR) by Local Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1, 2 & 3 | 18.2 percentage of participants |
| Phase I: 80 mg Fasted | Disease Control Rate (DCR) by Local Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1, 2 & 3 | 33.3 percentage of participants |
| Phase I: 80 mg Fed | Disease Control Rate (DCR) by Local Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1, 2 & 3 | 60.0 percentage of participants |
| Phase I: 120 mg Fasted | Disease Control Rate (DCR) by Local Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1, 2 & 3 | 50.0 percentage of participants |
| Phase I: 120 mg Fed | Disease Control Rate (DCR) by Local Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1, 2 & 3 | 47.4 percentage of participants |
| Phase I: 150 mg Fasted | Disease Control Rate (DCR) by Local Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1, 2 & 3 | 71.4 percentage of participants |
| Phase I: FGF401 80 mg + PDR001 300 mg | Disease Control Rate (DCR) by Local Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1, 2 & 3 | 50.0 percentage of participants |
| Phase I: FGF401 120 mg + PDR001 300 mg | Disease Control Rate (DCR) by Local Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1, 2 & 3 | 50.0 percentage of participants |
| Phase II: Group 1 - FGF401 120 mg QD | Disease Control Rate (DCR) by Local Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1, 2 & 3 | 43.3 percentage of participants |
| Phase II: Group 2 - FGF401 120 mg QD | Disease Control Rate (DCR) by Local Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1, 2 & 3 | 61.1 percentage of participants |
| PhaseII: Group 3 - FGF401 120 mg QD | Disease Control Rate (DCR) by Local Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1, 2 & 3 | 30.0 percentage of participants |
Secondary
Overall Response Rate (ORR) by Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1 & 2
ORR is defined as the proportion of patients with a best overall response of CR or PR (RECIST v1.1). Phase I part and FGF401 single agent Phase II Group 1 (HCC, Asians) and Group 2 (HCC, non-Asians)
Time frame: approx. 4.5 years
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Phase I: 50 mg Fasted | Overall Response Rate (ORR) by Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1 & 2 | 0 Percentage of participants |
| Phase I: 80 mg Fasted | Overall Response Rate (ORR) by Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1 & 2 | 16.7 Percentage of participants |
| Phase I: 80 mg Fed | Overall Response Rate (ORR) by Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1 & 2 | 20.0 Percentage of participants |
| Phase I: 120 mg Fasted | Overall Response Rate (ORR) by Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1 & 2 | 3.8 Percentage of participants |
| Phase I: 120 mg Fed | Overall Response Rate (ORR) by Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1 & 2 | 0 Percentage of participants |
| Phase I: 150 mg Fasted | Overall Response Rate (ORR) by Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1 & 2 | 14.3 Percentage of participants |
| Phase I: FGF401 80 mg + PDR001 300 mg | Overall Response Rate (ORR) by Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1 & 2 | 16.7 Percentage of participants |
| Phase I: FGF401 120 mg + PDR001 300 mg | Overall Response Rate (ORR) by Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1 & 2 | 16.7 Percentage of participants |
| Phase II: Group 1 - FGF401 120 mg QD | Overall Response Rate (ORR) by Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1 & 2 | 6.7 Percentage of participants |
| Phase II: Group 2 - FGF401 120 mg QD | Overall Response Rate (ORR) by Investigator Assessment Phase I and FGF401 Single Agent Phase II Groups 1 & 2 | 5.6 Percentage of participants |
Secondary
Overall Survival (OS) in Participants Dosed With Single Agent FGF401 120 mg (Fasted & Fed) and in Participants Dosed With Combination FGF401 120 mg and PDR001 300 mg Q3W (Phase I & II)
Overall survival (OS) is defined as the time from date of start of treatment to date of death due to any cause. If a patient was not known to have died, survival was censored at the date of last known date patient alive. Method used was Kaplan-Meier analysis.
Time frame: start of treatment to death, up to about 53 months
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I: 50 mg Fasted | 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) | 7.0 months |
| Phase I: 80 mg Fasted | 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) | 4.9 months |
| Phase I: 80 mg Fed | 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) | NA months |
| Phase I: 120 mg Fasted | 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) | 5.9 months |
| Phase I: 120 mg Fed | 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) | 10.9 months |
| Phase I: 150 mg Fasted | 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) | 6.2 months |
Secondary
Presence and/or Concentration of Anti-PDR001 Antibodies
Serum PDR001 concentrations as well as immunogenicity analysis were performed for all subjects receiving PDR001. Treatment-induced ADA-positive percentage was based on percentage subjects ADA-negative at baseline. Treatment-boosted ADA-positive percentage was based on subjects ADA-positive at baseline.
Time frame: Day 1 of Cycle 1 to 6, approx. 10 months after C1D1 and 150-day safety follow up (FU)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I: 50 mg Fasted | Presence and/or Concentration of Anti-PDR001 Antibodies | ADA-negative | 100.0 percentage of participants |
| Phase I: 50 mg Fasted | Presence and/or Concentration of Anti-PDR001 Antibodies | ADA-positive (i.e. ADA incidence) | 0 percentage of participants |
| Phase I: 50 mg Fasted | Presence and/or Concentration of Anti-PDR001 Antibodies | Treatment-induced ADA-positive | 0 percentage of participants |
| Phase I: 50 mg Fasted | Presence and/or Concentration of Anti-PDR001 Antibodies | Treatment-boosted ADA-positive | 0 percentage of participants |
| Phase I: 80 mg Fasted | Presence and/or Concentration of Anti-PDR001 Antibodies | Treatment-boosted ADA-positive | 0 percentage of participants |
| Phase I: 80 mg Fasted | Presence and/or Concentration of Anti-PDR001 Antibodies | ADA-negative | 83.3 percentage of participants |
| Phase I: 80 mg Fasted | Presence and/or Concentration of Anti-PDR001 Antibodies | Treatment-induced ADA-positive | 20.0 percentage of participants |
| Phase I: 80 mg Fasted | Presence and/or Concentration of Anti-PDR001 Antibodies | ADA-positive (i.e. ADA incidence) | 16.7 percentage of participants |
Secondary
Progression-free Survival (PFS) - FGF401 Single Agent Phase II: Group 3
Progression-free survival (PFS) is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. Group 3 - non-HCC, other solid tumors. Method used was Kaplan-Meier analysis.
Time frame: 4.5 years
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I: 50 mg Fasted | Progression-free Survival (PFS) - FGF401 Single Agent Phase II: Group 3 | 1.4 months |
Secondary
T1/2 of FGF401: Phase I
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)
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: 50 mg Fasted | T1/2 of FGF401: Phase I | C1D8 | 6.57 hour (hr) | Geometric Coefficient of Variation 16.6 |
| Phase I: 50 mg Fasted | T1/2 of FGF401: Phase I | C1D1 | 6.27 hour (hr) | Geometric Coefficient of Variation 16.2 |
| Phase I: 50 mg Fasted | T1/2 of FGF401: Phase I | C2D1 | 6.46 hour (hr) | Geometric Coefficient of Variation 18.9 |
| Phase I: 80 mg Fasted | T1/2 of FGF401: Phase I | C1D8 | 6.08 hour (hr) | Geometric Coefficient of Variation 13.8 |
| Phase I: 80 mg Fasted | T1/2 of FGF401: Phase I | C1D1 | 4.91 hour (hr) | Geometric Coefficient of Variation 31.6 |
| Phase I: 80 mg Fasted | T1/2 of FGF401: Phase I | C2D1 | 5.44 hour (hr) | Geometric Coefficient of Variation 34.9 |
| Phase I: 80 mg Fed | T1/2 of FGF401: Phase I | C1D8 | 5.58 hour (hr) | Geometric Coefficient of Variation 12 |
| Phase I: 80 mg Fed | T1/2 of FGF401: Phase I | C1D1 | 5.2 hour (hr) | Geometric Coefficient of Variation 8.8 |
| Phase I: 80 mg Fed | T1/2 of FGF401: Phase I | C2D1 | 5.43 hour (hr) | Geometric Coefficient of Variation 17.2 |
| Phase I: 120 mg Fasted | T1/2 of FGF401: Phase I | C2D1 | 5.8 hour (hr) | Geometric Coefficient of Variation 22.1 |
| Phase I: 120 mg Fasted | T1/2 of FGF401: Phase I | C1D1 | 5.47 hour (hr) | Geometric Coefficient of Variation 14.4 |
| Phase I: 120 mg Fasted | T1/2 of FGF401: Phase I | C1D8 | 5.43 hour (hr) | Geometric Coefficient of Variation 30 |
| Phase I: 120 mg Fed | T1/2 of FGF401: Phase I | C1D1 | 5.16 hour (hr) | Geometric Coefficient of Variation 16.3 |
| Phase I: 120 mg Fed | T1/2 of FGF401: Phase I | C1D8 | 5.58 hour (hr) | Geometric Coefficient of Variation 17.1 |
| Phase I: 120 mg Fed | T1/2 of FGF401: Phase I | C2D1 | 5.81 hour (hr) | Geometric Coefficient of Variation 20.2 |
| Phase I: 150 mg Fasted | T1/2 of FGF401: Phase I | C1D8 | 5.24 hour (hr) | Geometric Coefficient of Variation 12.4 |
| Phase I: 150 mg Fasted | T1/2 of FGF401: Phase I | C1D1 | 5 hour (hr) | Geometric Coefficient of Variation 11.3 |
| Phase I: 150 mg Fasted | T1/2 of FGF401: Phase I | C2D1 | 4.92 hour (hr) | Geometric Coefficient of Variation 14.4 |
Secondary
T1/2 of PDR001: Phase I
Due to the sparse PK sampling designed from PDR001, the PDR001 concentration data was insufficient for accurate estimation of secondary PK parameters including T1/2.
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
Population: 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.
Secondary
Time to Progression (TTP) in Participants Dosed With Single Agent FGF401 120 mg (Fasted & Fed) & With Combination FGF401 120 mg + PDR001 300 mg Q3W (Phase I)
TTP is defined as the date of start treatment to the date of event defined as the first documented progression or death due to underlying cancer. Method used was Kaplan-Meier analysis.
Time frame: approx. 4.5 years
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I: 50 mg Fasted | 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) | 4.1 months |
| Phase I: 80 mg Fasted | 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) | 2.0 months |
| Phase I: 80 mg Fed | 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) | 5.3 months |
Post Hoc
All Collected Deaths
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I: 50 mg Fasted | All Collected Deaths | Total deaths | 10 Participants |
| Phase I: 50 mg Fasted | All Collected Deaths | Deaths post-treatment survival follow up | 8 Participants |
| Phase I: 50 mg Fasted | All Collected Deaths | Deaths on-treatment | 2 Participants |
| Phase I: 80 mg Fasted | All Collected Deaths | Deaths post-treatment survival follow up | 4 Participants |
| Phase I: 80 mg Fasted | All Collected Deaths | Total deaths | 5 Participants |
| Phase I: 80 mg Fasted | All Collected Deaths | Deaths on-treatment | 1 Participants |
| Phase I: 80 mg Fed | All Collected Deaths | Deaths post-treatment survival follow up | 3 Participants |
| Phase I: 80 mg Fed | All Collected Deaths | Total deaths | 3 Participants |
| Phase I: 80 mg Fed | All Collected Deaths | Deaths on-treatment | 0 Participants |
| Phase I: 120 mg Fasted | All Collected Deaths | Deaths on-treatment | 4 Participants |
| Phase I: 120 mg Fasted | All Collected Deaths | Total deaths | 23 Participants |
| Phase I: 120 mg Fasted | All Collected Deaths | Deaths post-treatment survival follow up | 19 Participants |
| Phase I: 120 mg Fed | All Collected Deaths | Deaths post-treatment survival follow up | 6 Participants |
| Phase I: 120 mg Fed | All Collected Deaths | Total deaths | 12 Participants |
| Phase I: 120 mg Fed | All Collected Deaths | Deaths on-treatment | 6 Participants |
| Phase I: 150 mg Fasted | All Collected Deaths | Total deaths | 4 Participants |
| Phase I: 150 mg Fasted | All Collected Deaths | Deaths on-treatment | 1 Participants |
| Phase I: 150 mg Fasted | All Collected Deaths | Deaths post-treatment survival follow up | 3 Participants |
| Phase I: FGF401 80 mg + PDR001 300 mg | All Collected Deaths | Deaths post-treatment survival follow up | 18 Participants |
| Phase I: FGF401 80 mg + PDR001 300 mg | All Collected Deaths | Total deaths | 20 Participants |
| Phase I: FGF401 80 mg + PDR001 300 mg | All Collected Deaths | Deaths on-treatment | 2 Participants |
| Phase I: FGF401 120 mg + PDR001 300 mg | All Collected Deaths | Deaths on-treatment | 2 Participants |
| Phase I: FGF401 120 mg + PDR001 300 mg | All Collected Deaths | Total deaths | 22 Participants |
| Phase I: FGF401 120 mg + PDR001 300 mg | All Collected Deaths | Deaths post-treatment survival follow up | 20 Participants |
| Phase II: Group 1 - FGF401 120 mg QD | All Collected Deaths | Deaths on-treatment | 2 Participants |
| Phase II: Group 1 - FGF401 120 mg QD | All Collected Deaths | Deaths post-treatment survival follow up | 14 Participants |
| Phase II: Group 1 - FGF401 120 mg QD | All Collected Deaths | Total deaths | 16 Participants |
| Phase II: Group 2 - FGF401 120 mg QD | All Collected Deaths | Deaths on-treatment | 20 Participants |
| Phase II: Group 2 - FGF401 120 mg QD | All Collected Deaths | Total deaths | 115 Participants |
| Phase II: Group 2 - FGF401 120 mg QD | All Collected Deaths | Deaths post-treatment survival follow up | 95 Participants |
| PhaseII: Group 3 - FGF401 120 mg QD | All Collected Deaths | Deaths on-treatment | 0 Participants |
| PhaseII: Group 3 - FGF401 120 mg QD | All Collected Deaths | Deaths post-treatment survival follow up | 2 Participants |
| PhaseII: Group 3 - FGF401 120 mg QD | All Collected Deaths | Total deaths | 2 Participants |
| Phase I: FGF401 120 mg + PDR001 300 mg | All Collected Deaths | Deaths on-treatment | 0 Participants |
| Phase I: FGF401 120 mg + PDR001 300 mg | All Collected Deaths | Total deaths | 2 Participants |
| Phase I: FGF401 120 mg + PDR001 300 mg | All Collected Deaths | Deaths post-treatment survival follow up | 2 Participants |
| All Patients of Combination Dose | All Collected Deaths | Total deaths | 4 Participants |
| All Patients of Combination Dose | All Collected Deaths | Deaths post-treatment survival follow up | 4 Participants |
| All Patients of Combination Dose | All Collected Deaths | Deaths on-treatment | 0 Participants |
| All Patients | All Collected Deaths | Deaths post-treatment survival follow up | 99 Participants |
| All Patients | All Collected Deaths | Deaths on-treatment | 20 Participants |
| All Patients | All Collected Deaths | Total deaths | 119 Participants |