Trial Outcomes & Findings for Intermittent Checkpoint Inhibitor Therapy In Patients With Advanced Urothelial Carcinoma (NCT NCT04322643)

Last Updated: 2025-02-25

Results Overview

Efficiency, as measured by number of participants that sustain a response post CPI suspension. Response is defined as tumor burden reduction of 10% or greater. Response is measured based on RECIST criteria version 1.1. RECIST 1.1 responses include Complete Response (CR) which is defined as disappearance of all lesions and pathologic lymph nodes; Partial Response (PR) defined as ≥ 30% decrease SLD, no new lesions, no progression of non-target lesions; Stable disease (SD) which is defined as no partial or complete responses; or Progressive disease (PD) defined as ≥ 20% increase SLD compared to smallest SLD in study, or progression of non-target lesions, or new lesions.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

4 participants

Primary outcome timeframe

At 36 weeks post CPI suspension

Results posted on

2025-02-25

Participant Flow

Participant milestones

Participant milestones
Measure	CPI Therapy Patients will be treated with CPI therapy for at least 24 weeks (+/- 4 weeks) as per standard of care (SOC), at which time those with a tumor burden reduction of 10% or greater will suspend CPI therapy. Pembrolizumab: Pembrolizumab 200 mg IV over 30 minutes every 3 weeks Atezolizumab: Atezolizumab 1200 mg IV over 60 minutes every 3 weeks. (if first dose is tolerated, all subsequent infusions may be delivered over 30 minutes) Durvalumab: Durvalumab 10 mg/kg IV over 60 minutes every 2 weeks. Nivolumab: Nivolumab 480mg IV over 30 minutes every 4 weeks Avelumab: Avelumab 800 mg IV over 60 minutes every 2 weeks
Overall Study STARTED	4
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	CPI Therapy Patients will be treated with CPI therapy for at least 24 weeks (+/- 4 weeks) as per standard of care (SOC), at which time those with a tumor burden reduction of 10% or greater will suspend CPI therapy. Pembrolizumab: Pembrolizumab 200 mg IV over 30 minutes every 3 weeks Atezolizumab: Atezolizumab 1200 mg IV over 60 minutes every 3 weeks. (if first dose is tolerated, all subsequent infusions may be delivered over 30 minutes) Durvalumab: Durvalumab 10 mg/kg IV over 60 minutes every 2 weeks. Nivolumab: Nivolumab 480mg IV over 30 minutes every 4 weeks Avelumab: Avelumab 800 mg IV over 60 minutes every 2 weeks
Overall Study Study halted prematurely therefore treatment halted.	4

Baseline Characteristics

Intermittent Checkpoint Inhibitor Therapy In Patients With Advanced Urothelial Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CPI Therapy n=4 Participants Patients will be treated with CPI therapy for at least 24 weeks (+/- 4 weeks) as per standard of care (SOC), at which time those with a tumor burden reduction of 10% or greater will suspend CPI therapy. Pembrolizumab: Pembrolizumab 200 mg IV over 30 minutes every 3 weeks Atezolizumab: Atezolizumab 1200 mg IV over 60 minutes every 3 weeks. (if first dose is tolerated, all subsequent infusions may be delivered over 30 minutes) Durvalumab: Durvalumab 10 mg/kg IV over 60 minutes every 2 weeks. Nivolumab: Nivolumab 480mg IV over 30 minutes every 4 weeks Avelumab: Avelumab 800 mg IV over 60 minutes every 2 weeks
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	4 participants n=5 Participants

PRIMARY outcome

Timeframe: At 36 weeks post CPI suspension

Population: All four participants sustained a response after CPI therapy, but this study was terminated prematurely due to the changes in treatment landscape of advanced urothelial carcinoma.

Outcome measures

Outcome measures
Measure	CPI Therapy n=4 Participants Patients will be treated with CPI therapy for at least 24 weeks (+/- 4 weeks) as per standard of care (SOC), at which time those with a tumor burden reduction of 10% or greater will suspend CPI therapy. Pembrolizumab: Pembrolizumab 200 mg IV over 30 minutes every 3 weeks Atezolizumab: Atezolizumab 1200 mg IV over 60 minutes every 3 weeks. (if first dose is tolerated, all subsequent infusions may be delivered over 30 minutes) Durvalumab: Durvalumab 10 mg/kg IV over 60 minutes every 2 weeks. Nivolumab: Nivolumab 480mg IV over 30 minutes every 4 weeks Avelumab: Avelumab 800 mg IV over 60 minutes every 2 weeks
Number of Participants That Sustain a Response Post CPI Suspension	4 Participants

SECONDARY outcome

Timeframe: Up to 36 weeks from end of treatment, through study completion an average of 160 weeks

Population: Due to slow accrual and premature trial closure, data were incompletely collected and not analyzed, with no plans for future analysis. The true participant TFI is not available as this study terminated prematurely and ended follow up period. The outcome measure data is based on TFI at time of termination.

Median and range TFI in months. Participants will be treated with CPI therapy for at least 24 weeks (+/- 4 weeks) as per standard of care (SOC), at which time those with a tumor burden reduction of 10% or greater will suspend CPI therapy. Participants with a documented increase in ≥ 20% tumor burden (RECIST 1.1 PD) will re-initiate CPI. For those patients who continue to have response, they will remain off therapy.

Outcome measures

Outcome measures
Measure	CPI Therapy n=4 Participants Patients will be treated with CPI therapy for at least 24 weeks (+/- 4 weeks) as per standard of care (SOC), at which time those with a tumor burden reduction of 10% or greater will suspend CPI therapy. Pembrolizumab: Pembrolizumab 200 mg IV over 30 minutes every 3 weeks Atezolizumab: Atezolizumab 1200 mg IV over 60 minutes every 3 weeks. (if first dose is tolerated, all subsequent infusions may be delivered over 30 minutes) Durvalumab: Durvalumab 10 mg/kg IV over 60 minutes every 2 weeks. Nivolumab: Nivolumab 480mg IV over 30 minutes every 4 weeks Avelumab: Avelumab 800 mg IV over 60 minutes every 2 weeks
Median Treatment Free Interval (TFI) in Weeks	94.1 weeks Interval 36.1 to 106.8

SECONDARY outcome

Timeframe: Up to 36 weeks from end of treatment, through study completion an average of 160 weeks

Population: Due to slow accrual and premature trial closure, data were incompletely collected and not analyzed, with no plans for future analysis. All four participants sustained a response after CPI therapy, but this study was terminated prematurely due to the changes in treatment landscape of advanced urothelial carcinoma.

Response to re-initiation of CPI therapy as measured by overall response rate (ORR) defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed by RECIST 1.1

Outcome measures

Outcome measures
Measure	CPI Therapy n=4 Participants Patients will be treated with CPI therapy for at least 24 weeks (+/- 4 weeks) as per standard of care (SOC), at which time those with a tumor burden reduction of 10% or greater will suspend CPI therapy. Pembrolizumab: Pembrolizumab 200 mg IV over 30 minutes every 3 weeks Atezolizumab: Atezolizumab 1200 mg IV over 60 minutes every 3 weeks. (if first dose is tolerated, all subsequent infusions may be delivered over 30 minutes) Durvalumab: Durvalumab 10 mg/kg IV over 60 minutes every 2 weeks. Nivolumab: Nivolumab 480mg IV over 30 minutes every 4 weeks Avelumab: Avelumab 800 mg IV over 60 minutes every 2 weeks
Overall Response Rate (ORR) Partial Response	4 Participants
Overall Response Rate (ORR) Complete Response	0 Participants
Overall Response Rate (ORR) Stable Disease	0 Participants
Overall Response Rate (ORR) Progressive Disease	0 Participants

SECONDARY outcome

Timeframe: Up to 36 weeks from end of treatment, through study completion an average of 160 weeks

Population: 4/4 patients remained progression-free survival at the time of study termination.

Progression free survival (PFS) defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first as assessed by RECIST 1.1 criteria. PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm and the appearance of ≥1 new lesions is also considered PD.

Outcome measures

Outcome measures
Measure	CPI Therapy n=4 Participants Patients will be treated with CPI therapy for at least 24 weeks (+/- 4 weeks) as per standard of care (SOC), at which time those with a tumor burden reduction of 10% or greater will suspend CPI therapy. Pembrolizumab: Pembrolizumab 200 mg IV over 30 minutes every 3 weeks Atezolizumab: Atezolizumab 1200 mg IV over 60 minutes every 3 weeks. (if first dose is tolerated, all subsequent infusions may be delivered over 30 minutes) Durvalumab: Durvalumab 10 mg/kg IV over 60 minutes every 2 weeks. Nivolumab: Nivolumab 480mg IV over 30 minutes every 4 weeks Avelumab: Avelumab 800 mg IV over 60 minutes every 2 weeks
Number of Participants With Progression Free Survival (PFS)	4 Participants

SECONDARY outcome

Timeframe: Up to 36 weeks from end of treatment, through study completion an average of 160 weeks

Population: 4/4 participants were alive at the time of study termination.

Overall Survival (OS) defined as the time from randomization to death due to any cause

Outcome measures

Outcome measures
Measure	CPI Therapy n=4 Participants Patients will be treated with CPI therapy for at least 24 weeks (+/- 4 weeks) as per standard of care (SOC), at which time those with a tumor burden reduction of 10% or greater will suspend CPI therapy. Pembrolizumab: Pembrolizumab 200 mg IV over 30 minutes every 3 weeks Atezolizumab: Atezolizumab 1200 mg IV over 60 minutes every 3 weeks. (if first dose is tolerated, all subsequent infusions may be delivered over 30 minutes) Durvalumab: Durvalumab 10 mg/kg IV over 60 minutes every 2 weeks. Nivolumab: Nivolumab 480mg IV over 30 minutes every 4 weeks Avelumab: Avelumab 800 mg IV over 60 minutes every 2 weeks
Number of Participants With Overall Survival (OS)	4 Participants

Adverse Events

CPI Therapy

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Moshe Ornstein

Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center

Phone: 866-223-8100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place