Advanced and Metastatic Urothelial Cancer
Conditions
Keywords
Futibatinib, Pembrolizumab, Urothelial cancer, FGFR, TAS120, MK3475 B04
Brief summary
The purpose of the trial is to evaluate the antitumor activity and confirm the safety for the combination of Fibroblast Growth Factor Receptor (FGFR) inhibitor futibatinib and anti-programmed cell death-1 (PD-1) antibody pembrolizumab in patients with advanced or metastatic urothelial cancer who are not candidates to receive a platinum-based treatment regimens.
Interventions
DRUGFutibatinib
Oral
DRUGPembrolizumab
IV
Sponsors
Merck Sharp & Dohme LLC
Taiho Oncology, Inc.
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. Willing and able to provide written informed consent for the trial. 2. Age ≥ 18 years of age 3. Histologically confirmed advanced or metastatic urothelial carcinoma who have not received systemic treatment for advanced metastatic disease. 1. Cohort A: must have an FGFR3 mutation or FGFR1-4 fusion/rearrangement. 2. Cohort B: all other patients with UC (including patients with other FGFR or non-FGFR genetic aberrations and patients with wild-type \[non-mutated\] tumors) 4. Unfit for or intolerant to standard platinum-based chemotherapy. 5. Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1. 6. Adequate organ function. 7. Have a measurable disease per RECIST 1.1
Exclusion criteria
1. Have received prior therapy with anti-PD-1, anti-PD-L1/L2 agent or FGFR inhibitor. 2. History and/or current evidence of any of the following disorders: 1. Non-tumor related alteration of the calcium-phosphorus homeostasis that is considered clinically significant in the opinion of the Investigator. 2. Ectopic mineralization/calcification considered clinically significant in the opinion of the Investigator. 3. Retinal or corneal disorder considered clinically significant in the opinion of the Investigator. 3. Has received a live vaccine within 30 days prior to the first dose of study drug. 4. Have an active autoimmune disease that has required systemic treatment in the past 2 years. 5. Have a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis. 6. Have had an allogenic tissue/ organ transplant. 7. Has known human immunodeficiency virus (HIV) and/or history of Hepatitis B or C infections, or known to be positive for Hepatitis B antigen (HBsAg)/ Hepatitis B virus (HBV) DNA or Hepatitis C Antibody or RNA. 8. Have known active central nervous system metastases and/or carcinomatous meningitis. 9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy. 10. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to 38 months | ORR was defined as the proportion of participants experiencing a best overall response of partial response (PR) or complete response (CR) according to response evaluation criteria in solid tumors, version 1.1 (RECIST 1.1) criteria based on investigator assessment. Evaluation of target lesions defined a CR as the disappearance of all target lesions and non-target lesions (if applicable), and normalization of tumor marker level; PR was defined as at least a 30 percent (%) decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum of diameters for all target lesion assessments. Evaluation of non-target lesions was defined as the persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. For both target and non-target evaluations, any pathological lymph node must have had a reduction in short axis to less than (\<)10 millimeters (mm). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | Up to 38 months | DCR was defined as the proportion of participants experiencing a best overall response of SD, PR, or CR. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), referencing the smallest sum diameters while on study. Evaluation of target lesions defined a CR as the disappearance of all target lesions and non-target lesions (if applicable), and normalization of tumor marker level; PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum of diameters for all target lesion assessments. Evaluation of non-target lesions was defined as the persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. For both target and non-target evaluations, any pathological lymph node must have had a reduction in short axis \<10 mm. |
| Duration of Response (DOR) | Up to 38 months | DOR was calculated for all responders from the date of first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurred first. Evaluation of target lesions defined a CR as the disappearance of all target lesions and non-target lesions (if applicable), and normalization of tumor marker level; PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum of diameters for all target lesion assessments. Evaluation of non-target lesions was defined as the persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. For both target and non-target evaluations, any pathological lymph node must have had a reduction in short axis to \<10 mm. |
| Progression-free Survival (PFS) | Up to 38 months | PFS was defined as the time from the first dose of study therapy to the date of death (any cause) or disease progression, whichever occurred first. The PFS was analyzed using a Kaplan-Meier method, with PFS time being censored on the date of the last tumor assessment. The 95% confidence interval (CI) for median PFS was provided using the Kaplan-Meier procedure. |
| Overall Survival (OS) | Up to 38 months | OS was defined as the time from the date of the first dose to the death date. Participants without a documented death date were censored on the last date they were known to be alive. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Up to 38 months | An adverse event (AE) is defined as any untoward medical occurrence in a clinical study participant and does not necessarily have a causal relationship with the study drug. TEAEs are defined as AEs reported up to 30 days after the last dose of any study therapy (safety follow-up) or until the start of new antitumor therapy, whichever is earlier, unless otherwise specified. |
Countries
France, Spain, United States
Participant flow
Recruitment details
Participants took part in the study at 18 sites in the United States, France and Spain from 07 January 2021 to 16 September 2025.
Pre-assignment details
A total of 43 participants were enrolled to receive futibatinib along with pembrolizumab.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A Participants with metastatic urothelial carcinoma (UC) and FGFR3 mutation or FGFR1-4 fusion/rearrangement received futibatinib 20 milligrams (mg), orally, once daily (QD), in a 21-day cycle for maximum duration of 590 days along with pembrolizumab 200 mg, intravenously (IV), every 3 weeks (Q3W), in a 21-day cycle for a maximum of 35 doses or a maximum duration of 2 years. | 17 |
| Cohort B Participants with metastatic UC (including participants with other FGFR or non-FGFR genetic aberrations and participants with wild type \[non-mutated\] tumors) received futibatinib 20 mg, orally, QD, in a 21-day cycle for maximum duration of 563 days along with pembrolizumab 200 mg, IV, Q3W in a 21-day cycle for a maximum of 35 doses or a maximum duration of 2 years. | 26 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event/Serious Adverse Event | 3 | 7 |
| Overall Study | At the Participant's Request | 0 | 1 |
| Overall Study | Clinical Disease Progression | 2 | 1 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Disease Progression | 2 | 4 |
| Overall Study | Radiological Progression | 4 | 11 |
| Overall Study | Reason Not Specified | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort A | Cohort B | Total |
|---|---|---|---|
| Age, Continuous | 73.1 years STANDARD_DEVIATION 9.86 | 72.2 years STANDARD_DEVIATION 10.03 | 72.6 years STANDARD_DEVIATION 9.86 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 17 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants | 8 Participants | 15 Participants |
| Race/Ethnicity, Customized Black/African American | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Caucasian/White | 7 Participants | 15 Participants | 22 Participants |
| Race/Ethnicity, Customized Not Reported | 9 Participants | 9 Participants | 18 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 14 Participants | 23 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 17 | 13 / 26 |
| other Total, other adverse events | 17 / 17 | 26 / 26 |
| serious Total, serious adverse events | 10 / 17 | 12 / 26 |
Outcome results
Primary
Objective Response Rate (ORR)
ORR was defined as the proportion of participants experiencing a best overall response of partial response (PR) or complete response (CR) according to response evaluation criteria in solid tumors, version 1.1 (RECIST 1.1) criteria based on investigator assessment. Evaluation of target lesions defined a CR as the disappearance of all target lesions and non-target lesions (if applicable), and normalization of tumor marker level; PR was defined as at least a 30 percent (%) decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum of diameters for all target lesion assessments. Evaluation of non-target lesions was defined as the persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. For both target and non-target evaluations, any pathological lymph node must have had a reduction in short axis to less than (\<)10 millimeters (mm).
Time frame: Up to 38 months
Population: All treated population included all participants in all enrolled population who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A | Objective Response Rate (ORR) | 47.1 percentage of participants |
| Cohort B | Objective Response Rate (ORR) | 26.9 percentage of participants |
Secondary
Disease Control Rate (DCR)
DCR was defined as the proportion of participants experiencing a best overall response of SD, PR, or CR. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), referencing the smallest sum diameters while on study. Evaluation of target lesions defined a CR as the disappearance of all target lesions and non-target lesions (if applicable), and normalization of tumor marker level; PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum of diameters for all target lesion assessments. Evaluation of non-target lesions was defined as the persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. For both target and non-target evaluations, any pathological lymph node must have had a reduction in short axis \<10 mm.
Time frame: Up to 38 months
Population: All treated population included all participants in all enrolled population who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A | Disease Control Rate (DCR) | 82.4 percentage of participants |
| Cohort B | Disease Control Rate (DCR) | 53.8 percentage of participants |
Secondary
Duration of Response (DOR)
DOR was calculated for all responders from the date of first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurred first. Evaluation of target lesions defined a CR as the disappearance of all target lesions and non-target lesions (if applicable), and normalization of tumor marker level; PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum of diameters for all target lesion assessments. Evaluation of non-target lesions was defined as the persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. For both target and non-target evaluations, any pathological lymph node must have had a reduction in short axis to \<10 mm.
Time frame: Up to 38 months
Population: All treated population included all participants in all enrolled population who received at least one dose of study drug. Overall number of participants analyzed is the number of participants with data available for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A | Duration of Response (DOR) | 12.32 months |
| Cohort B | Duration of Response (DOR) | 14.46 months |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) is defined as any untoward medical occurrence in a clinical study participant and does not necessarily have a causal relationship with the study drug. TEAEs are defined as AEs reported up to 30 days after the last dose of any study therapy (safety follow-up) or until the start of new antitumor therapy, whichever is earlier, unless otherwise specified.
Time frame: Up to 38 months
Population: All treated population included all participants in all enrolled population who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 17 Participants |
| Cohort B | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 26 Participants |
Secondary
Overall Survival (OS)
OS was defined as the time from the date of the first dose to the death date. Participants without a documented death date were censored on the last date they were known to be alive.
Time frame: Up to 38 months
Population: All treated population included all participants in all enrolled population who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A | Overall Survival (OS) | 16.2 months |
| Cohort B | Overall Survival (OS) | 18.3 months |
Secondary
Progression-free Survival (PFS)
PFS was defined as the time from the first dose of study therapy to the date of death (any cause) or disease progression, whichever occurred first. The PFS was analyzed using a Kaplan-Meier method, with PFS time being censored on the date of the last tumor assessment. The 95% confidence interval (CI) for median PFS was provided using the Kaplan-Meier procedure.
Time frame: Up to 38 months
Population: All treated population included all participants in all enrolled population who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A | Progression-free Survival (PFS) | 8.3 months |
| Cohort B | Progression-free Survival (PFS) | 4.1 months |