Metastatic Urothelial Carcinoma
Conditions
Brief summary
Study of the Combination of ACP-196 and Pembrolizumab in Subjects With Platinum Resistant Metastatic Urothelial Cancer
Interventions
DRUGpembrolizumab
Sponsors
Merck Sharp & Dohme LLC
Acerta Pharma BV
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men and women ≥ 18 years of age * Histologically or cytologically confirmed urothelial carcinoma of the bladder or mixed histology bladder cancer * Metastatic bladder cancer with disease progression on or after platinum-based chemotherapy * Any primary site of urothelial carcinoma including upper tract, renal pelvis, bladder, and ureters * Prior therapy with ≥ 1 systemic chemotherapy regimens for urothelial carcinoma * Presence of radiographically measurable disease (defined as the presence of ≥ 1 lesion that measures ≥ 10 mm \[≥ 15 mm for lymph nodes\] * ECOG performance status of 0 or 1
Exclusion criteria
* Prior malignancy (other than bladder cancer), except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for ≥ 2 years of which will not limit survival to \< 2 years. * Known central nervous system metastases and/or carcinomatous meningitis * Malabsorption syndrome, disease significantly affecting gastrointestinal function * Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Overall Response | Every 12 weeks for up to 2 years. | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab Arm 1: pembrolizumab monotherapy
pembrolizumab | 35 |
| ACP-196 in Combination With Pembrolizumab Arm 2: ACP-196 in combination with pembrolizumab
ACP-196 in combination with pembrolizumab | 40 |
| Total | 75 |
Baseline characteristics
| Characteristic | ACP-196 in Combination With Pembrolizumab | Total | Pembrolizumab |
|---|---|---|---|
| Age, Continuous | 66.4 Years STANDARD_DEVIATION 8.53 | 66.1 Years STANDARD_DEVIATION 9.74 | 65.8 Years STANDARD_DEVIATION 11.08 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 74 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 37 Participants | 69 Participants | 32 Participants |
| Sex: Female, Male Female | 29 Participants | 57 Participants | 28 Participants |
| Sex: Female, Male Male | 11 Participants | 18 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 25 / 35 | 31 / 40 |
| other Total, other adverse events | 34 / 35 | 39 / 40 |
| serious Total, serious adverse events | 15 / 35 | 23 / 40 |
Outcome results
Primary
Number of Participants With Overall Response
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: Every 12 weeks for up to 2 years.
Population: The study participants had to have a minimum of one scan (for tumor assessment) after randomization/treatment in order to be considered analyzed.~And some of the participants didn't make it to Wk 7 of treatment, hence reduction in the number of subjects analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab | Number of Participants With Overall Response | 9 Participants |
| ACP-196 in Combination With Pembrolizumab | Number of Participants With Overall Response | 8 Participants |