Trial Outcomes & Findings for Oral Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations (NCT NCT04197986)

NCT ID: NCT04197986

Last Updated: 2024-03-13

Results Overview

DFS was defined as the number of months from date of randomization to local/regional invasive or metastatic recurrence or death due to any cause (referred as DFS event), whichever occurs earlier. Due to early termination of the study by the sponsor, results will focus primarily on the primary and key secondary endpoints of the study. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

39 participants

Primary outcome timeframe

The number of months from date of randomization to local/regional invasive or metastatic recurrence or death due to any cause.

Results posted on

2024-03-13

Participant Flow

Participants with a diagnosis of invasive urothelial carcinoma were recruited to this double-blind, randomized, placebo-controlled global study across 30 study centers (11 in North America, and 19 in Western Europe) based on documented evidence of FGFR3 genetic alteration. The first participant was treated on 18 March 2020. The data cutoff for the primary analysis was 28 February 2023.

Subjects meeting inclusion/exclusion criteria were randomly assigned 1:1 to receive oral infigratinib 125 mg (N=20) or placebo (N=19). Randomization was stratified by lymph node involvement (yes/no), prior neoadjuvant cisplatin chemotherapy (yes/no), stage (pT2 vs \> pT2), and disease (upper tract urothelial carcinoma \[UTUC\] vs urinary bladder cancer \[UBC\]).

Participant milestones

Participant milestones
Measure	Infigratinib 125 mg Participants were randomly assigned (1:1) to receive oral infigratinib administered once daily for the first 3 weeks (21 days) of each 28-day cycle for a maximum of 52 weeks. Infigratinib: Participants randomly assigned to infigratinib received hard gelatin capsules for oral administration of infigratinib 125 mg once a day (administered as one 100-mg capsule and one 25-mg capsule) using a 3 weeks on (Days 1-21) /1 week off (Days 22-28) dosing schedule.	Placebo Participants were randomly assigned (1:1) to receive oral placebo administered once daily for the first 3 weeks (21 days) of each 28-day cycle for a maximum of 52 weeks. Placebo: Participants randomly assigned to placebo received placebo matching in appearance the investigational product (infigratinib) provided as hard gelatin capsules for oral use and administered once daily on a 3 weeks on (Days 1-21) /1 week off (Days 22-28) dosing schedule.
Overall Study STARTED	20	19
Overall Study Treatment Ended	20	19
Overall Study COMPLETED	20	19
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Not available for 3 participants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Infigratinib n=20 Participants 125 mg oral infigratinib once daily for the first 3 weeks (21 days) of each 28-day cycle	Placebo n=19 Participants Placebo once daily for the first 3 weeks (21 days) of a 28-day treatment cycle	Total n=39 Participants Total of all reporting groups
Age, Categorical Age Group · <=18 years	0 Participants n=20 Participants	0 Participants n=19 Participants	0 Participants n=39 Participants
Age, Categorical Age Group · Between 18 and 65 years	8 Participants n=20 Participants	4 Participants n=19 Participants	12 Participants n=39 Participants
Age, Categorical Age Group · >=65 years	12 Participants n=20 Participants	15 Participants n=19 Participants	27 Participants n=39 Participants
Age, Continuous	66.1 years STANDARD_DEVIATION 12.10 • n=20 Participants	69.7 years STANDARD_DEVIATION 12.75 • n=19 Participants	67.8 years STANDARD_DEVIATION 12.39 • n=39 Participants
Sex: Female, Male Female	2 Participants n=20 Participants	4 Participants n=19 Participants	6 Participants n=39 Participants
Sex: Female, Male Male	18 Participants n=20 Participants	15 Participants n=19 Participants	33 Participants n=39 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=20 Participants	0 Participants n=19 Participants	0 Participants n=39 Participants
Race (NIH/OMB) Asian	1 Participants n=20 Participants	0 Participants n=19 Participants	1 Participants n=39 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=20 Participants	0 Participants n=19 Participants	0 Participants n=39 Participants
Race (NIH/OMB) Black or African American	1 Participants n=20 Participants	0 Participants n=19 Participants	1 Participants n=39 Participants
Race (NIH/OMB) White	17 Participants n=20 Participants	16 Participants n=19 Participants	33 Participants n=39 Participants
Race (NIH/OMB) More than one race	0 Participants n=20 Participants	2 Participants n=19 Participants	2 Participants n=39 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=20 Participants	1 Participants n=19 Participants	2 Participants n=39 Participants
Region of Enrollment North America	8 participants n=20 Participants	6 participants n=19 Participants	14 participants n=39 Participants
Region of Enrollment Europe	12 participants n=20 Participants	13 participants n=19 Participants	25 participants n=39 Participants
BMI	27.78 kg/m2 STANDARD_DEVIATION 4.882 • n=19 Participants • Not available for 3 participants	26.05 kg/m2 STANDARD_DEVIATION 4.793 • n=17 Participants • Not available for 3 participants	26.96 kg/m2 STANDARD_DEVIATION 4.850 • n=36 Participants • Not available for 3 participants
ECOG PS 0	15 Participants n=20 Participants	11 Participants n=19 Participants	26 Participants n=39 Participants
ECOG PS 1	5 Participants n=20 Participants	8 Participants n=19 Participants	13 Participants n=39 Participants
Primary Site of Cancer UTUC	11 Participants n=20 Participants	12 Participants n=19 Participants	23 Participants n=39 Participants
Primary Site of Cancer UBC	9 Participants n=20 Participants	7 Participants n=19 Participants	16 Participants n=39 Participants
Histological Subtype Urothelial	11 Participants n=20 Participants	7 Participants n=19 Participants	18 Participants n=39 Participants
Histological Subtype Papillary urothelial	7 Participants n=20 Participants	8 Participants n=19 Participants	15 Participants n=39 Participants
Histological Subtype Mixed	2 Participants n=20 Participants	4 Participants n=19 Participants	6 Participants n=39 Participants
Screening Diagnosis Category (Pathologic Stage at Definitive Surgery) - Tumor (T) T1	0 Participants n=20 Participants	1 Participants n=19 Participants	1 Participants n=39 Participants
Screening Diagnosis Category (Pathologic Stage at Definitive Surgery) - Tumor (T) T2	7 Participants n=20 Participants	5 Participants n=19 Participants	12 Participants n=39 Participants
Screening Diagnosis Category (Pathologic Stage at Definitive Surgery) - Tumor (T) T3	12 Participants n=20 Participants	11 Participants n=19 Participants	23 Participants n=39 Participants
Screening Diagnosis Category (Pathologic Stage at Definitive Surgery) - Tumor (T) T4	1 Participants n=20 Participants	2 Participants n=19 Participants	3 Participants n=39 Participants
Screening Diagnosis Category (Pathologic Stage at Definitive Surgery) - Node (N) NX	8 Participants n=20 Participants	6 Participants n=19 Participants	14 Participants n=39 Participants
Screening Diagnosis Category (Pathologic Stage at Definitive Surgery) - Node (N) N0	9 Participants n=20 Participants	8 Participants n=19 Participants	17 Participants n=39 Participants
Screening Diagnosis Category (Pathologic Stage at Definitive Surgery) - Node (N) N1	1 Participants n=20 Participants	3 Participants n=19 Participants	4 Participants n=39 Participants
Screening Diagnosis Category (Pathologic Stage at Definitive Surgery) - Node (N) N2	2 Participants n=20 Participants	2 Participants n=19 Participants	4 Participants n=39 Participants
Time from Initial Diagnosis to Randomization (Days)	166.2 days STANDARD_DEVIATION 91.15 • n=20 Participants	393.7 days STANDARD_DEVIATION 837.30 • n=19 Participants	277.0 days STANDARD_DEVIATION 591.19 • n=39 Participants
Type of FGFR3 Alteration (Local) Mutation	1 Participants n=20 Participants	0 Participants n=19 Participants	1 Participants n=39 Participants
Type of FGFR3 Alteration (Local) Fusion	0 Participants n=20 Participants	2 Participants n=19 Participants	2 Participants n=39 Participants
Type of FGFR3 Alteration (Local) Rearrangement	0 Participants n=20 Participants	0 Participants n=19 Participants	0 Participants n=39 Participants
Type of FGFR3 Alteration (Local) Not available	19 Participants n=20 Participants	17 Participants n=19 Participants	36 Participants n=39 Participants
FGFR3 Mutation Result (Local) G370C	1 Participants n=20 Participants	0 Participants n=19 Participants	1 Participants n=39 Participants
FGFR3 Mutation Result (Local) Not available	19 Participants n=20 Participants	19 Participants n=19 Participants	38 Participants n=39 Participants
FGFR3 Fusion Result (Local) Fusion Positive - Fusion partner known	0 Participants n=20 Participants	1 Participants n=19 Participants	1 Participants n=39 Participants
FGFR3 Fusion Result (Local) Not available	20 Participants n=20 Participants	18 Participants n=19 Participants	38 Participants n=39 Participants
Type FGFR3 Alteration (Central) Mutation	13 Participants n=20 Participants	13 Participants n=19 Participants	26 Participants n=39 Participants
Type FGFR3 Alteration (Central) Fusion	6 Participants n=20 Participants	4 Participants n=19 Participants	10 Participants n=39 Participants
Type FGFR3 Alteration (Central) Rearrangement	0 Participants n=20 Participants	0 Participants n=19 Participants	0 Participants n=39 Participants
Type FGFR3 Alteration (Central) Not available	1 Participants n=20 Participants	2 Participants n=19 Participants	3 Participants n=39 Participants
FGFR3 Mutation Result (Central) G370C	0 Participants n=20 Participants	1 Participants n=19 Participants	1 Participants n=39 Participants
FGFR3 Mutation Result (Central) K650E	1 Participants n=20 Participants	0 Participants n=19 Participants	1 Participants n=39 Participants
FGFR3 Mutation Result (Central) R248C	1 Participants n=20 Participants	2 Participants n=19 Participants	3 Participants n=39 Participants
FGFR3 Mutation Result (Central) S249C	9 Participants n=20 Participants	7 Participants n=19 Participants	16 Participants n=39 Participants
FGFR3 Mutation Result (Central) Y373C	2 Participants n=20 Participants	3 Participants n=19 Participants	5 Participants n=39 Participants
FGFR3 Mutation Result (Central) Not available	7 Participants n=20 Participants	6 Participants n=19 Participants	13 Participants n=39 Participants
FGFR3 Fusion Result (Central) Y	6 Participants n=20 Participants	4 Participants n=19 Participants	10 Participants n=39 Participants
FGFR3 Fusion Result (Central) Not available	14 Participants n=20 Participants	15 Participants n=19 Participants	29 Participants n=39 Participants
Tumor Mutational Burden Low	17 Participants n=20 Participants	13 Participants n=19 Participants	30 Participants n=39 Participants
Tumor Mutational Burden High	2 Participants n=20 Participants	3 Participants n=19 Participants	5 Participants n=39 Participants
Tumor Mutational Burden Unknown	0 Participants n=20 Participants	2 Participants n=19 Participants	2 Participants n=39 Participants
Tumor Mutational Burden Cannot be determined	0 Participants n=20 Participants	1 Participants n=19 Participants	1 Participants n=39 Participants
Tumor Mutational Burden Not available	1 Participants n=20 Participants	0 Participants n=19 Participants	1 Participants n=39 Participants

PRIMARY outcome

Timeframe: The number of months from date of randomization to local/regional invasive or metastatic recurrence or death due to any cause.

Population: Intent-to-treat (ITT) population, which included all subjects who were randomized

Outcome measures

Outcome measures
Measure	Infigratinib 125 mg n=3 Participants Infigratinib 125 mg once daily (3 weeks on / 1 week off treatment)	Placebo n=2 Participants Placebo once daily (3 weeks on / 1 week off treatment)
Centrally Determined Disease-free Survival (DFS)	5.3 Months Interval 0.03 to 17.48	5.4 Months Interval 0.03 to 20.9

SECONDARY outcome

Timeframe: The number of months from date of randomization to local/regional invasive or metastatic recurrence or death due to any cause.

Population: ITT population includes all subjects who were randomized

DFS was defined as the number of months from date of randomization to local/regional invasive or metastatic recurrence or death due to any cause (referred as DFS event), whichever occurs earlier. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.

Outcome measures

Outcome measures
Measure	Infigratinib 125 mg n=7 Participants Infigratinib 125 mg once daily (3 weeks on / 1 week off treatment)	Placebo n=3 Participants Placebo once daily (3 weeks on / 1 week off treatment)
Investigator-assessed DFS	6.39 Months Interval 0.03 to 18.07	12.22 Months Interval 0.03 to 21.36

SECONDARY outcome

Timeframe: The time from randomization to any metastatic recurrence as determined by the investigator, or death due to any cause.

Population: ITT Population

MFS was defined as the time from randomization to any metastatic recurrence as determined by the investigator, or death due to any cause, whichever occurred earlier. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.

Outcome measures

Outcome measures
Measure	Infigratinib 125 mg n=3 Participants Infigratinib 125 mg once daily (3 weeks on / 1 week off treatment)	Placebo n=2 Participants Placebo once daily (3 weeks on / 1 week off treatment)
Metastasis-free Survival (MFS)	6.5 Months Interval 0.03 to 18.07	12.2 Months Interval 0.03 to 21.36

SECONDARY outcome

Timeframe: The number of months from randomization to death.

Population: ITT population

Overall survival time was defined as the number of months from randomization to death. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.

Outcome measures

Outcome measures
Measure	Infigratinib 125 mg n=20 Participants Infigratinib 125 mg once daily (3 weeks on / 1 week off treatment)	Placebo n=19 Participants Placebo once daily (3 weeks on / 1 week off treatment)
Overall Survival (OS)	13.1 Months Interval 0.76 to 32.07	16.7 Months Interval 1.22 to 31.57

SECONDARY outcome

Timeframe: The number of months from date of randomization to local/regional invasive or metastatic recurrence or death due to any cause.

Population: ITT population

Investigator assessment of intraluminal low-risk recurrence as assessed by DFS. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.

Outcome measures

Outcome measures
Measure	Infigratinib 125 mg n=7 Participants Infigratinib 125 mg once daily (3 weeks on / 1 week off treatment)	Placebo n=4 Participants Placebo once daily (3 weeks on / 1 week off treatment)
Investigator-reviewed DFS Including Intraluminal Low-Risk Recurrence	5.29 Months Interval 0.03 to 18.07	5.62 Months Interval 0.03 to 20.9

SECONDARY outcome

Timeframe: From first dose to last dose of study treatment +30 days (an average of 4 months for the infigratinib arm and 8 months for the placebo arm).

Population: Safety Population

Number of participants with AEs

Outcome measures

Outcome measures
Measure	Infigratinib 125 mg n=20 Participants Infigratinib 125 mg once daily (3 weeks on / 1 week off treatment)	Placebo n=19 Participants Placebo once daily (3 weeks on / 1 week off treatment)
Number of Participants With Adverse Events (AEs)	19 Participants	16 Participants

SECONDARY outcome

Timeframe: From first dose to last dose of study treatment +30 days (an average of 4 months for the infigratinib arm and 8 months for the placebo arm)

Population: Safety Population

Number of Participants with SAEs

Outcome measures

Outcome measures
Measure	Infigratinib 125 mg n=20 Participants Infigratinib 125 mg once daily (3 weeks on / 1 week off treatment)	Placebo n=19 Participants Placebo once daily (3 weeks on / 1 week off treatment)
Number of Participants With Serious Adverse Events (SAEs)	2 Participants	2 Participants

Adverse Events

Infigratinib 125 mg

Serious events: 2 serious events

Other events: 19 other events

Deaths: 2 deaths

Placebo

Serious events: 2 serious events

Other events: 16 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Infigratinib 125 mg n=20 participants at risk Infigratinib 125 mg once daily (3 weeks on / 1 week off treatment)	Placebo n=19 participants at risk Placebo once daily (3 weeks on / 1 week off treatment)
Gastrointestinal disorders Diarrhoea	10.0% 2/20 • From first administration of study treatment and up to last administration of study treatment + 30 days (an average of 4 months for the infigratinib arm and 8 months for the placebo arm). AEs were assessed by the investigator according to the CTCAE version 5.0 and coded using MedDRA version 23.1. Treatment-emergent AEs are reported and include all AEs with onset after the first administration of study treatment and up to last administration of study treatment + 30 days if subjects ended study treatment. For a subject who had not ended study treatment, all the AEs after the first administration of study drug were considered treatment-emergent.	0.00% 0/19 • From first administration of study treatment and up to last administration of study treatment + 30 days (an average of 4 months for the infigratinib arm and 8 months for the placebo arm). AEs were assessed by the investigator according to the CTCAE version 5.0 and coded using MedDRA version 23.1. Treatment-emergent AEs are reported and include all AEs with onset after the first administration of study treatment and up to last administration of study treatment + 30 days if subjects ended study treatment. For a subject who had not ended study treatment, all the AEs after the first administration of study drug were considered treatment-emergent.
Gastrointestinal disorders Vomiting	5.0% 1/20 • From first administration of study treatment and up to last administration of study treatment + 30 days (an average of 4 months for the infigratinib arm and 8 months for the placebo arm). AEs were assessed by the investigator according to the CTCAE version 5.0 and coded using MedDRA version 23.1. Treatment-emergent AEs are reported and include all AEs with onset after the first administration of study treatment and up to last administration of study treatment + 30 days if subjects ended study treatment. For a subject who had not ended study treatment, all the AEs after the first administration of study drug were considered treatment-emergent.	0.00% 0/19 • From first administration of study treatment and up to last administration of study treatment + 30 days (an average of 4 months for the infigratinib arm and 8 months for the placebo arm). AEs were assessed by the investigator according to the CTCAE version 5.0 and coded using MedDRA version 23.1. Treatment-emergent AEs are reported and include all AEs with onset after the first administration of study treatment and up to last administration of study treatment + 30 days if subjects ended study treatment. For a subject who had not ended study treatment, all the AEs after the first administration of study drug were considered treatment-emergent.
Infections and infestations Urosepsis	0.00% 0/20 • From first administration of study treatment and up to last administration of study treatment + 30 days (an average of 4 months for the infigratinib arm and 8 months for the placebo arm). AEs were assessed by the investigator according to the CTCAE version 5.0 and coded using MedDRA version 23.1. Treatment-emergent AEs are reported and include all AEs with onset after the first administration of study treatment and up to last administration of study treatment + 30 days if subjects ended study treatment. For a subject who had not ended study treatment, all the AEs after the first administration of study drug were considered treatment-emergent.	5.3% 1/19 • From first administration of study treatment and up to last administration of study treatment + 30 days (an average of 4 months for the infigratinib arm and 8 months for the placebo arm). AEs were assessed by the investigator according to the CTCAE version 5.0 and coded using MedDRA version 23.1. Treatment-emergent AEs are reported and include all AEs with onset after the first administration of study treatment and up to last administration of study treatment + 30 days if subjects ended study treatment. For a subject who had not ended study treatment, all the AEs after the first administration of study drug were considered treatment-emergent.
Metabolism and nutrition disorders Dehydration	5.0% 1/20 • From first administration of study treatment and up to last administration of study treatment + 30 days (an average of 4 months for the infigratinib arm and 8 months for the placebo arm). AEs were assessed by the investigator according to the CTCAE version 5.0 and coded using MedDRA version 23.1. Treatment-emergent AEs are reported and include all AEs with onset after the first administration of study treatment and up to last administration of study treatment + 30 days if subjects ended study treatment. For a subject who had not ended study treatment, all the AEs after the first administration of study drug were considered treatment-emergent.	0.00% 0/19 • From first administration of study treatment and up to last administration of study treatment + 30 days (an average of 4 months for the infigratinib arm and 8 months for the placebo arm). AEs were assessed by the investigator according to the CTCAE version 5.0 and coded using MedDRA version 23.1. Treatment-emergent AEs are reported and include all AEs with onset after the first administration of study treatment and up to last administration of study treatment + 30 days if subjects ended study treatment. For a subject who had not ended study treatment, all the AEs after the first administration of study drug were considered treatment-emergent.
Renal and urinary disorders Chronic kidney disease	5.0% 1/20 • From first administration of study treatment and up to last administration of study treatment + 30 days (an average of 4 months for the infigratinib arm and 8 months for the placebo arm). AEs were assessed by the investigator according to the CTCAE version 5.0 and coded using MedDRA version 23.1. Treatment-emergent AEs are reported and include all AEs with onset after the first administration of study treatment and up to last administration of study treatment + 30 days if subjects ended study treatment. For a subject who had not ended study treatment, all the AEs after the first administration of study drug were considered treatment-emergent.	0.00% 0/19 • From first administration of study treatment and up to last administration of study treatment + 30 days (an average of 4 months for the infigratinib arm and 8 months for the placebo arm). AEs were assessed by the investigator according to the CTCAE version 5.0 and coded using MedDRA version 23.1. Treatment-emergent AEs are reported and include all AEs with onset after the first administration of study treatment and up to last administration of study treatment + 30 days if subjects ended study treatment. For a subject who had not ended study treatment, all the AEs after the first administration of study drug were considered treatment-emergent.
Renal and urinary disorders Urinary tract obstruction	0.00% 0/20 • From first administration of study treatment and up to last administration of study treatment + 30 days (an average of 4 months for the infigratinib arm and 8 months for the placebo arm). AEs were assessed by the investigator according to the CTCAE version 5.0 and coded using MedDRA version 23.1. Treatment-emergent AEs are reported and include all AEs with onset after the first administration of study treatment and up to last administration of study treatment + 30 days if subjects ended study treatment. For a subject who had not ended study treatment, all the AEs after the first administration of study drug were considered treatment-emergent.	5.3% 1/19 • From first administration of study treatment and up to last administration of study treatment + 30 days (an average of 4 months for the infigratinib arm and 8 months for the placebo arm). AEs were assessed by the investigator according to the CTCAE version 5.0 and coded using MedDRA version 23.1. Treatment-emergent AEs are reported and include all AEs with onset after the first administration of study treatment and up to last administration of study treatment + 30 days if subjects ended study treatment. For a subject who had not ended study treatment, all the AEs after the first administration of study drug were considered treatment-emergent.
Vascular disorders Lymphocele	0.00% 0/20 • From first administration of study treatment and up to last administration of study treatment + 30 days (an average of 4 months for the infigratinib arm and 8 months for the placebo arm). AEs were assessed by the investigator according to the CTCAE version 5.0 and coded using MedDRA version 23.1. Treatment-emergent AEs are reported and include all AEs with onset after the first administration of study treatment and up to last administration of study treatment + 30 days if subjects ended study treatment. For a subject who had not ended study treatment, all the AEs after the first administration of study drug were considered treatment-emergent.	5.3% 1/19 • From first administration of study treatment and up to last administration of study treatment + 30 days (an average of 4 months for the infigratinib arm and 8 months for the placebo arm). AEs were assessed by the investigator according to the CTCAE version 5.0 and coded using MedDRA version 23.1. Treatment-emergent AEs are reported and include all AEs with onset after the first administration of study treatment and up to last administration of study treatment + 30 days if subjects ended study treatment. For a subject who had not ended study treatment, all the AEs after the first administration of study drug were considered treatment-emergent.

Other adverse events

Additional Information

Acting Chief Medical Officer

QED Therapeutics, Inc.

Phone: 1-877-280-5655

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place