Trial Outcomes & Findings for Pembrolizumab in Intermediate Risk Recurrent Non-muscle Invasive Bladder Cancer (NMIBC) (NCT NCT03167151)

Last Updated: 2020-07-31

Results Overview

Adverse events are categorised according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Patients with intermediate risk Non-muscle Invasive Bladder Cancer (NMIBC) were assessed for dose limiting toxicity (DLT) and tolerability. Administration of at least 5 out of 6 treatments was required for the regime to be defined as tolerable.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

6 participants

Primary outcome timeframe

Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy.

Results posted on

2020-07-31

Participant Flow

Initially, the plan was to recruit the 6 participants for the safety run-in phase of the study within 6 months. 9 patients, of which 6 were evaluable, were recruited at the Oxford Churchill Hospital site from 02 Mar 2018 until 31 Jan 2019. Due to the issues with slow recruitment, the steering committee decided to end recruitment on 31 Jan 2019

9 participants were recruited onto the study. However, of the 9 participants, 2 were found to have no tumour present during their surgery and were therefore no longer eligible. A further 1 participant withdrew their consent after they had been recruited. Thus of 9 participants only 6 were eligible for analysis.

Participant milestones

Participant milestones
Measure	Safety run-in Phase Cohort 1 Cohort 1 in the safety run-in phase. Day 1 starting dose 50mg intravesical pembrolizumab	Safety run-in Phase Cohort 2 Cohort 2 in the safety run-in phase. Day 1 starting dose 100mg intravesical pembrolizumab	Safety run-in Phase Cohort 3 Cohort 3 in the safety run-in phase. Day 1 starting dose 200mg intravesical pembrolizumab
Overall Study STARTED	3	3	3
Overall Study COMPLETED	2	2	2
Overall Study NOT COMPLETED	1	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Safety run-in Phase Cohort 1 Cohort 1 in the safety run-in phase. Day 1 starting dose 50mg intravesical pembrolizumab	Safety run-in Phase Cohort 2 Cohort 2 in the safety run-in phase. Day 1 starting dose 100mg intravesical pembrolizumab	Safety run-in Phase Cohort 3 Cohort 3 in the safety run-in phase. Day 1 starting dose 200mg intravesical pembrolizumab
Overall Study Withdrawal by Subject	1	0	0
Overall Study No evidence of tumour at surgery	0	1	1

Baseline Characteristics

Pembrolizumab in Intermediate Risk Recurrent Non-muscle Invasive Bladder Cancer (NMIBC)

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy.

Population: Six patients received at least 5 out of 6 scheduled treatments, or withdrew early due to drug-related toxicity, and hence these patients contributed to the DLT and tolerability analysis.

Outcome measures

Outcome measures
Measure	Safety run-in Phase Cohort 1 n=2 Participants Cohort 1 in the safety run-in phase. Day 1 starting dose 50mg intravesical pembrolizumab	Safety run-in Phase Cohort 2 n=2 Participants Cohort 2 in the safety run-in phase. Day 1 starting dose 100mg intravesical pembrolizumab	Safety run-in Phase Cohort 3 n=2 Participants Cohort 3 in the safety run-in phase. Day 1 starting dose 200mg intravesical pembrolizumab
Number of Dose Limiting Toxicities (DLTs) to Assess the Safety, Tolerability and Toxicities of Intravesical Pembrolizumab After Transurethral Resection of Bladder Tumour (TURBT).	0 DLTs	0 DLTs	0 DLTs

OTHER_PRE_SPECIFIED outcome

Timeframe: Day -14 TURBT, optional Day 50 TURBT, Day 85 TURBT and where applicable optional follow-up period ≤ 24 months

Pre treatment, during treatment (optional), and post treatment tumour samples Immunohistochemistry and Fluorescence-activated cell sorting (FACS) analysis to measure. Additionally, collection of an optional tumour sample at the time of recurrence or progression for research purposes will be performed if the patient provides consent for this. The optional tumour sample would be collected at the time of a standard care surveillance cystoscopy or resection if the patient had a repeat TURBT in standard care.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 pre-treatment

Gene expression profiling and DNA sequencing on pre-treatment blood and tumour samples to predict efficacy of pembrolizumab treatment in NMIBC patients.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 to 92

Evaluating the effects of pembrolizumab treatment on the immunological profile and tumour specific immune responses in patients with intermediate risk NMIBC.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 to 92

Identification of myeloid or T cell responses in the tumour microenvironment associated with the response to treatment with pembrolizumab.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 to 92

Identification of myeloid or T cell responses in the tumour microenvironment associated with response to treatment

Outcome measures

Outcome data not reported

Adverse Events

Safety run-in Phase Cohort 1

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Safety run-in Phase Cohort 2

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Safety run-in Phase Cohort 3

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Safety run-in Phase Cohort 1 n=2 participants at risk Cohort 1 in the safety run-in phase. Day 1 starting dose 50mg intravesical pembrolizumab	Safety run-in Phase Cohort 2 n=2 participants at risk Cohort 2 in the safety run-in phase. Day 1 starting dose 100mg intravesical pembrolizumab	Safety run-in Phase Cohort 3 n=2 participants at risk Cohort 3 in the safety run-in phase. Day 1 starting dose 200mg intravesical pembrolizumab
Infections and infestations Urosepsis	50.0% 1/2 • Number of events 1 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.

Other adverse events

Other adverse events
Measure	Safety run-in Phase Cohort 1 n=2 participants at risk Cohort 1 in the safety run-in phase. Day 1 starting dose 50mg intravesical pembrolizumab	Safety run-in Phase Cohort 2 n=2 participants at risk Cohort 2 in the safety run-in phase. Day 1 starting dose 100mg intravesical pembrolizumab	Safety run-in Phase Cohort 3 n=2 participants at risk Cohort 3 in the safety run-in phase. Day 1 starting dose 200mg intravesical pembrolizumab
Infections and infestations Cystitis	50.0% 1/2 • Number of events 1 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.
Nervous system disorders Dizziness	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	50.0% 1/2 • Number of events 1 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.
Renal and urinary disorders Dysuria	50.0% 1/2 • Number of events 1 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	50.0% 1/2 • Number of events 1 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.
General disorders Fatigue	50.0% 1/2 • Number of events 1 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	50.0% 1/2 • Number of events 1 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.
General disorders Fever	50.0% 1/2 • Number of events 1 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.
Renal and urinary disorders Haematuria	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	50.0% 1/2 • Number of events 1 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.
Vascular disorders Hot flushes	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	50.0% 1/2 • Number of events 2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.
Skin and subcutaneous tissue disorders Itching	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	50.0% 1/2 • Number of events 1 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.
Gastrointestinal disorders Nausea	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	50.0% 1/2 • Number of events 1 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.
Skin and subcutaneous tissue disorders Rash	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	50.0% 1/2 • Number of events 1 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.
General disorders Rigors	50.0% 1/2 • Number of events 1 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.
Renal and urinary disorders Urgency-Frequency Syndrome	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	50.0% 1/2 • Number of events 3 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.
Infections and infestations Urinary Tract Infection	100.0% 2/2 • Number of events 2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	0.00% 0/2 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.	50.0% 1/2 • Number of events 1 • Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy. The investigator monitored each patient for clinical and laboratory evidence of adverse events on a routine basis throughout the study.

Additional Information

Dr Andrew S Protheroe

Oxford University Hospitals NHS Foundation Trust

Phone: 01865 253275

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Safety run-in Phase Cohort 1 n=2 Participants Cohort 1 in the safety run-in phase. Day 1 starting dose 50mg intravesical pembrolizumab	Safety run-in Phase Cohort 2 n=2 Participants Cohort 2 in the safety run-in phase. Day 1 starting dose 100mg intravesical pembrolizumab	Safety run-in Phase Cohort 3 n=2 Participants Cohort 3 in the safety run-in phase. Day 1 starting dose 200mg intravesical pembrolizumab	Total n=6 Participants Total of all reporting groups
Age, Continuous	73 years STANDARD_DEVIATION 0 • n=5 Participants	66 years STANDARD_DEVIATION 10.6 • n=7 Participants	81 years STANDARD_DEVIATION 7.8 • n=5 Participants	73 years STANDARD_DEVIATION 8.9 • n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized White British	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Smoking status Current	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Smoking status Ex-smoker	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Smoking status Never smoked	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Performance Status 0	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Performance Status 1	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Site of primary tumour Bladder	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Site of primary tumour Left renal pelvis	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Site of primary tumour Urothelial	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Prior chemotherapy Yes	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Prior chemotherapy No	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Prior surgery Yes	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Prior surgery No	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants