Trial Outcomes & Findings for Basket Trial in Solid Tumors Harboring a Fusion of FGFR1, FGFR2 or FGFR3- (FUZE Clinical Trial) (NCT NCT03834220)

Last Updated: 2024-02-07

Results Overview

ORR was defined as the percentage of participants with a best overall response (BOR) of partial or complete response (PR or CR). BOR was defined as the best confirmed response observed from first administration of study drug until disease progression. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

63 participants

Primary outcome timeframe

Up to disease progression or end of study (up to 1 year and 9 months)

Results posted on

2024-02-07

Participant Flow

A total of 63 participants were enrolled at 31 investigational sites in the United States, France, Spain, Finland, Korea, Singapore, Australia, Bulgaria, Denmark, Norway, Russian Federation, Taiwan, and the United Kingdom from 22 March 2019 to 04 January 2022.

A total of 63 participants with solid tumors harboring FGFR1-3 gene fusion/rearrangement were enrolled into one of the 3 cohorts: Cohort 1: Biliary Tract Cancer (N=30), Cohort 2: Urothelial Cancer (N=4), Cohort 3: All Other Solid Tumor Histologies (N=29) to receive Debio 1347.

Participant milestones

Participant milestones
Measure	Cohort 1: Debio 1347 (Biliary Tract Cancer) Participants with biliary tract cancer were included in this cohort to receive Debio 1347 80 milligrams (mg) tablets, orally, once daily (QD), from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 20 weeks).	Cohort 2: Debio 1347 (Urothelial Cancer) Participants with urothelial cancer were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 5.86 weeks)	Cohort 3: Debio 1347 (All Other Solid Tumor Histologies) Participants with all other solid tumor histologies were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 8.14 weeks).
Overall Study STARTED	30	4	29
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	30	4	29

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1: Debio 1347 (Biliary Tract Cancer) Participants with biliary tract cancer were included in this cohort to receive Debio 1347 80 milligrams (mg) tablets, orally, once daily (QD), from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 20 weeks).	Cohort 2: Debio 1347 (Urothelial Cancer) Participants with urothelial cancer were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 5.86 weeks)	Cohort 3: Debio 1347 (All Other Solid Tumor Histologies) Participants with all other solid tumor histologies were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 8.14 weeks).
Overall Study Adverse Event	1	0	0
Overall Study Death	8	1	17
Overall Study Reason not Specified	9	0	6
Overall Study Sponsor/EthicsCommittee Decided to Terminate Study	10	1	4
Overall Study Withdrawal of Consent	2	2	2

Baseline Characteristics

Basket Trial in Solid Tumors Harboring a Fusion of FGFR1, FGFR2 or FGFR3- (FUZE Clinical Trial)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: Debio 1347 (Biliary Tract Cancer) n=30 Participants Participants with biliary tract cancer were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 20 weeks).	Cohort 2: Debio 1347 (Urothelial Cancer) n=4 Participants Participants with urothelial cancer were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 5.86 weeks).	Cohort 3: Debio 1347 (All Other Solid Tumor Histologies) n=29 Participants Participants with all other solid tumor histologies were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 8.14 weeks).	Total n=63 Participants Total of all reporting groups
Age, Continuous	59.1 years STANDARD_DEVIATION 12.21 • n=5 Participants	55.3 years STANDARD_DEVIATION 15.22 • n=7 Participants	60.0 years STANDARD_DEVIATION 12.58 • n=5 Participants	59.3 years STANDARD_DEVIATION 12.40 • n=4 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	2 Participants n=7 Participants	16 Participants n=5 Participants	34 Participants n=4 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	2 Participants n=7 Participants	13 Participants n=5 Participants	29 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=5 Participants	4 Participants n=7 Participants	28 Participants n=5 Participants	61 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized White	20 Participants n=5 Participants	3 Participants n=7 Participants	22 Participants n=5 Participants	45 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	5 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized Asian	3 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Race/Ethnicity, Customized Not Willing to Provide	1 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to disease progression or end of study (up to 1 year and 9 months)

Population: ITT Population consisted of all participants who received study drug. Overall number of participants analyzed is the number of participants with measurable disease and tumor assessment at Baseline.

Outcome measures

Outcome measures
Measure	Cohort 1: Debio 1347 (Biliary Tract Cancer) n=30 Participants Participants with biliary tract cancer were included in this cohort to receive Debio 1347 80 mg tablets, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 20 weeks).	Cohort 2: Debio 1347 (Urothelial Cancer) n=3 Participants Participants with urothelial cancer were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 5.86 weeks).	Cohort 3: Debio 1347 (All Other Solid Tumor Histologies) n=25 Participants Participants with all other solid tumor histologies were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 8.14 weeks).
Objective Response Rate (ORR) as Centrally Measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Criteria	6.7 percentage of participants Interval 1.2 to 19.5	0 percentage of participants Interval 0.0 to 63.2	4.0 percentage of participants Interval 0.2 to 17.6

SECONDARY outcome

Timeframe: Up to disease progression or end of study (up to 2 years and 9 months)

Population: ITT Population consisted of all participants who received study drug. Only participants with best overall response of CR or PR were analyzed for this endpoint.

DOR was defined as the time from the date of the initial PR or CR to date of the first documented progression or death due to any cause. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Cohort 1: Debio 1347 (Biliary Tract Cancer) Participants with biliary tract cancer were included in this cohort to receive Debio 1347 80 mg tablets, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 20 weeks).	Cohort 2: Debio 1347 (Urothelial Cancer) Participants with urothelial cancer were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 5.86 weeks).	Cohort 3: Debio 1347 (All Other Solid Tumor Histologies) n=1 Participants Participants with all other solid tumor histologies were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 8.14 weeks).
Duration of Response (DOR) as Centrally Measured by Independent Review Committee (IRC)	—	—	5.55 months The lower and upper limit of 95% confidence interval (CI) were not estimable due to insufficient number of participants with event.

SECONDARY outcome

Timeframe: Up to disease progression or end of study (up to 2 years and 9 months)

Population: ITT population consisted of all participants who received study drug. Percentages are rounded off to the nearest single decimal point.

DCR was defined as the percentage of participants with a BOR of confirmed CR, confirmed PR or stable disease (SD) ≥6 weeks. BOR was defined as the best confirmed response observed from first administration of study drug until disease progression. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.

Outcome measures

Outcome measures
Measure	Cohort 1: Debio 1347 (Biliary Tract Cancer) n=30 Participants Participants with biliary tract cancer were included in this cohort to receive Debio 1347 80 mg tablets, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 20 weeks).	Cohort 2: Debio 1347 (Urothelial Cancer) n=4 Participants Participants with urothelial cancer were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 5.86 weeks).	Cohort 3: Debio 1347 (All Other Solid Tumor Histologies) n=29 Participants Participants with all other solid tumor histologies were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 8.14 weeks).
Disease Control Rate (DCR) as Centrally Measured by Independent Review Committee (IRC)	63.3 percentage of participants Interval 43.9 to 80.1	0 percentage of participants Interval 0.0 to 60.2	34.5 percentage of participants Interval 17.9 to 54.3

SECONDARY outcome

Timeframe: From the start of the study up to disease progression or death (up to 2 years and 9 months)

Population: ITT population consisted of all participants who received study drug.

PFS was defined as the time from the start date of treatment to date of the first documented progression or death due to any cause.

Outcome measures

Outcome measures
Measure	Cohort 1: Debio 1347 (Biliary Tract Cancer) n=30 Participants Participants with biliary tract cancer were included in this cohort to receive Debio 1347 80 mg tablets, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 20 weeks).	Cohort 2: Debio 1347 (Urothelial Cancer) n=4 Participants Participants with urothelial cancer were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 5.86 weeks).	Cohort 3: Debio 1347 (All Other Solid Tumor Histologies) n=29 Participants Participants with all other solid tumor histologies were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 8.14 weeks).
Progression-Free Survival (PFS) as Centrally Measured by Independent Review Committee (IRC)	3.68 months Interval 3.55 to 10.58	1.77 months Interval 0.95 to The upper limit of 95% CI was not estimable due to insufficient number of participants with event.	1.84 months Interval 1.71 to 3.52

SECONDARY outcome

Timeframe: Until death or loss to follow-up or end of study (up to 2 years and 9 months)

Population: ITT population consisted of all participants who received study drug.

OS was defined as the time from the start date of treatment to date of death due to any cause. Participants with no documented death were censored at the last date known to be alive.

Outcome measures

Outcome measures
Measure	Cohort 1: Debio 1347 (Biliary Tract Cancer) n=30 Participants Participants with biliary tract cancer were included in this cohort to receive Debio 1347 80 mg tablets, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 20 weeks).	Cohort 2: Debio 1347 (Urothelial Cancer) n=4 Participants Participants with urothelial cancer were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 5.86 weeks).	Cohort 3: Debio 1347 (All Other Solid Tumor Histologies) n=29 Participants Participants with all other solid tumor histologies were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 8.14 weeks).
Overall Survival (OS)	NA months The median, lower and upper limit of 95% CI were not estimable due to insufficient number of participants with events.	NA months The median, lower and upper limit of 95% CI were not estimable due to insufficient number of participants with events.	7.13 months Interval 4.3 to 11.37

SECONDARY outcome

Timeframe: From first dose of study drug up to 30 days post last dose (Up to 2 years and 9 months)

Population: Safety Population consisted of all participants who received study drug.

An AE is any untoward medical occurrence in a participant or clinical trial participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A TEAE is defined as an AE that either starts or worsens in severity on or after the first administration of the study drug and within 30 days of the last administration of the study drug. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Outcome measures

Outcome measures
Measure	Cohort 1: Debio 1347 (Biliary Tract Cancer) n=30 Participants Participants with biliary tract cancer were included in this cohort to receive Debio 1347 80 mg tablets, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 20 weeks).	Cohort 2: Debio 1347 (Urothelial Cancer) n=4 Participants Participants with urothelial cancer were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 5.86 weeks).	Cohort 3: Debio 1347 (All Other Solid Tumor Histologies) n=29 Participants Participants with all other solid tumor histologies were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 8.14 weeks).
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Assessed by National Cancer Institute Common Terminology Criteria (NCI CTCAE) v5.0 and Serious Adverse Events (SAEs) TEAEs	30 Participants	4 Participants	28 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Assessed by National Cancer Institute Common Terminology Criteria (NCI CTCAE) v5.0 and Serious Adverse Events (SAEs) Serious TEAEs	14 Participants	2 Participants	7 Participants

SECONDARY outcome

Timeframe: Predose and post dose up to Cycle 2 Day 28 (each cycle length = 28 days)

Population: Pharmacokinetic (PK) Population included participants who received one or more doses of Debio 1347 and have at least one PK concentration result available. Overall number of participants analyzed is the number of participants with data available for analysis.

Geometric mean and geometric percent CV summary was estimated based on log-linear model.

Outcome measures

Outcome measures
Measure	Cohort 1: Debio 1347 (Biliary Tract Cancer) n=30 Participants Participants with biliary tract cancer were included in this cohort to receive Debio 1347 80 mg tablets, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 20 weeks).	Cohort 2: Debio 1347 (Urothelial Cancer) n=3 Participants Participants with urothelial cancer were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 5.86 weeks).	Cohort 3: Debio 1347 (All Other Solid Tumor Histologies) n=26 Participants Participants with all other solid tumor histologies were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 8.14 weeks).
Trough Concentration at Steady State (Ctrough,ss) of Debio 1347 in Plasma	619.6 nanogram per millilitre (ng/mL) Geometric Coefficient of Variation 100.0	306.8 nanogram per millilitre (ng/mL) Geometric Coefficient of Variation 43.4	463.2 nanogram per millilitre (ng/mL) Geometric Coefficient of Variation 127.3

SECONDARY outcome

Timeframe: Predose and post dose up to Cycle 2 Day 28 (each cycle length = 28 days)

Population: PK Population included participants who received one or more doses of Debio 1347 and have at least one PK concentration result available. Overall number of participants analyzed is the number of participants with data available for analyses.

Geometric mean and geometric percent CV summary was estimated based on log-linear model.

Outcome measures

Outcome measures
Measure	Cohort 1: Debio 1347 (Biliary Tract Cancer) n=30 Participants Participants with biliary tract cancer were included in this cohort to receive Debio 1347 80 mg tablets, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 20 weeks).	Cohort 2: Debio 1347 (Urothelial Cancer) n=3 Participants Participants with urothelial cancer were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 5.86 weeks).	Cohort 3: Debio 1347 (All Other Solid Tumor Histologies) n=26 Participants Participants with all other solid tumor histologies were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 8.14 weeks).
Area Under the Plasma Concentration-Time Curve Over the Dosing Interval at Steady State (AUCtau,ss) of Debio 1347 in Plasma	23326.7 hournanogram (hng)/mL Geometric Coefficient of Variation 70.4	13999.0 hournanogram (hng)/mL Geometric Coefficient of Variation 39.1	18192.1 hournanogram (hng)/mL Geometric Coefficient of Variation 86.2

SECONDARY outcome

Timeframe: Pre-dose on Days 14 and 28, and 1, 3, 7 hours post-dose on Day 28 of Cycle 1; pre-dose on Days 14 and 28, and 3 hours post-dose on Day 28 of Cycle 2 (each cycle length = 28 days)

Population: The study was terminated by sponsor and thus the analysis for this outcome measure was not deemed necessary and no data was collected.

Outcome measures

Outcome data not reported

Adverse Events

Cohort 1: Debio 1347 (Biliary Tract Cancer)

Serious events: 14 serious events

Other events: 30 other events

Deaths: 9 deaths

Cohort 2: Debio 1347 (Urothelial Cancer)

Serious events: 2 serious events

Other events: 4 other events

Deaths: 1 deaths

Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)

Serious events: 7 serious events

Other events: 28 other events

Deaths: 17 deaths

Serious adverse events

Other adverse events

Additional Information

Head Clinical Research & Development

Debiopharm International S.A.

Phone: 4121 321 01 11

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Any publication or scientific communication related to this study can only take place once the agreement between the Sponsor and the Investigator has been reached.
Publication restrictions are in place

Restriction type: OTHER