Trial Outcomes & Findings for Durvalumab Plus Tremelimumab With Concurrent Radiotherapy for Localized Muscle Invasive Bladder Cancer Treated With a Selective Bladder Preservation Approach (NCT NCT03702179)
NCT ID: NCT03702179
Last Updated: 2024-12-05
Results Overview
Pathological response is defined as the absence of muscle- invasive bladder cancer at post-treatment biopsy (≤cT1). Cystoscopy and bladder biopsy six weeks since the end of radiotherapy.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
32 participants
Primary outcome timeframe
12 weeks
Results posted on
2024-12-05
Participant Flow
Participant milestones
| Measure |
Durvalumab + Tremelimumab
The treatment consisted of initial TUR of the tumor, with multiple random biopsies of normal-appearing bladder urothelium, followed by durvalumab 1500 mg i.v. plus tremelimumab 75 mg i.v., every 4 weeks for a total of 3 doses.
Durvalumab: All patients will receive durvalumab (MEDI4736) (1500mg Q4W) in combination with tremelimumab (75 mg IV Q4W) for up to 3 doses/cycles each, unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. If a patient's weight falls to 30kg or below the patient should receive weight-based dosing equivalent to 20 mg/kg of durvalumab Q4W and 1mg/kg tremelimumab Q4W until the weight improves to \>30 kg, at which point the patient should start receiving the fixed dosing of durvalumab 1500mg plus tremelimumab 75 mg Q4W.
Tremelimumab: All patients will receive durvalumab (MEDI4736) (1500mg Q4W) in combination with tremelimumab (75 mg IV Q4W) for up to 3 doses/cycles each, unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. If a patient's weight falls to 30kg or below the patient should receive weight-based dosing equivalent to 20 mg/kg of durvalumab Q4W and 1mg/kg tremelimumab Q4W until the weight improves to \>30 kg, at which point the patient should start receiving the fixed dosing of durvalumab 1500mg plus tremelimumab 75 mg Q4W.
Radiotherapy 46 Gy to the minor pelvis and 64-66 Gy to the bladder.
|
|---|---|
|
Overall Study
STARTED
|
32
|
|
Overall Study
COMPLETED
|
32
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Durvalumab Plus Tremelimumab With Concurrent Radiotherapy for Localized Muscle Invasive Bladder Cancer Treated With a Selective Bladder Preservation Approach
Baseline characteristics by cohort
| Measure |
Durvalumab + Tremelimumab
n=32 Participants
The treatment consisted of initial TUR of the tumor, with multiple random biopsies of normal-appearing bladder urothelium, followed by durvalumab 1500 mg i.v. plus tremelimumab 75 mg i.v., every 4 weeks for a total of 3 doses.
Durvalumab: All patients will receive durvalumab (MEDI4736) (1500mg Q4W) in combination with tremelimumab (75 mg IV Q4W) for up to 3 doses/cycles each, unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. If a patient's weight falls to 30kg or below the patient should receive weight-based dosing equivalent to 20 mg/kg of durvalumab Q4W and 1mg/kg tremelimumab Q4W until the weight improves to \>30 kg, at which point the patient should start receiving the fixed dosing of durvalumab 1500mg plus tremelimumab 75 mg Q4W.
Tremelimumab: All patients will receive durvalumab (MEDI4736) (1500mg Q4W) in combination with tremelimumab (75 mg IV Q4W) for up to 3 doses/cycles each, unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. If a patient's weight falls to 30kg or below the patient should receive weight-based dosing equivalent to 20 mg/kg of durvalumab Q4W and 1mg/kg tremelimumab Q4W until the weight improves to \>30 kg, at which point the patient should start receiving the fixed dosing of durvalumab 1500mg plus tremelimumab 75 mg Q4W.
Radiotherapy 46 Gy to the minor pelvis and 64-66 Gy to the bladder.
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|---|---|
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Age, Continuous
|
71 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
25 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
|
32 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
|
|
Eastern Cooperative Oncology Group Performance Status (ECOG-PS)
ECOG 0
|
25 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group Performance Status (ECOG-PS)
ECOG 1
|
7 Participants
n=5 Participants
|
|
Histology
Urothelial carcinoma
|
31 Participants
n=5 Participants
|
|
Histology
Mixed urothelial carcinoma
|
1 Participants
n=5 Participants
|
|
Clinical T stage
T2
|
28 Participants
n=5 Participants
|
|
Clinical T stage
T3
|
3 Participants
n=5 Participants
|
|
Clinical T stage
T4
|
1 Participants
n=5 Participants
|
|
Previous bladder cancer non-muscle invasive
Yes
|
14 Participants
n=5 Participants
|
|
Previous bladder cancer non-muscle invasive
No
|
18 Participants
n=5 Participants
|
|
Previous treatment
Bacillus Calmette-Guérin (BCG)
|
9 Participants
n=5 Participants
|
|
Previous treatment
Mitomycin
|
1 Participants
n=5 Participants
|
|
Previous treatment
Transurethral Resection of Bladder Tumor (TURBT)
|
1 Participants
n=5 Participants
|
|
Previous treatment
No treatment
|
21 Participants
n=5 Participants
|
|
PD-L1 expression
Positive
|
15 Participants
n=5 Participants
|
|
PD-L1 expression
Negative
|
12 Participants
n=5 Participants
|
|
PD-L1 expression
Unknown
|
5 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 weeksPathological response is defined as the absence of muscle- invasive bladder cancer at post-treatment biopsy (≤cT1). Cystoscopy and bladder biopsy six weeks since the end of radiotherapy.
Outcome measures
| Measure |
Durvalumab + Tremelimumab
n=28 Participants
Experimental arm:
Durvalumab 1500 mg i.v. plus tremelimumab 75 mg i.v., every 4 weeks for a total of 3 doses Radiotherapy 46 Gy to the minor pelvis and 64-66 Gy to the bladder.
|
|---|---|
|
Proportion of Patients With Pathological Response
Complete Response (≤T1)
|
26 Participants
|
|
Proportion of Patients With Pathological Response
Non-response (MIBC)
|
2 Participants
|
SECONDARY outcome
Timeframe: 24 monthsNumber of patients whom bladder has been preserved after cytoscopic evaluation.
Outcome measures
| Measure |
Durvalumab + Tremelimumab
n=28 Participants
Experimental arm:
Durvalumab 1500 mg i.v. plus tremelimumab 75 mg i.v., every 4 weeks for a total of 3 doses Radiotherapy 46 Gy to the minor pelvis and 64-66 Gy to the bladder.
|
|---|---|
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Rate of Patients With Bladder Preserved
Preserved bladder
|
28 Participants
|
|
Rate of Patients With Bladder Preserved
Not preserved bladder
|
0 Participants
|
SECONDARY outcome
Timeframe: 24 monthsNumber of patients with indication of salvage cystectomies after first trial-related cystoscopic evaluation.
Outcome measures
| Measure |
Durvalumab + Tremelimumab
n=32 Participants
Experimental arm:
Durvalumab 1500 mg i.v. plus tremelimumab 75 mg i.v., every 4 weeks for a total of 3 doses Radiotherapy 46 Gy to the minor pelvis and 64-66 Gy to the bladder.
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|---|---|
|
Rate of Immediate Salvage Cystectomies
Radical cystectomy performed
|
1 Participants
|
|
Rate of Immediate Salvage Cystectomies
Radical cystectomy not required
|
31 Participants
|
SECONDARY outcome
Timeframe: 24 monthsNumber of patients with indication of salvage cystectomies based on follow-up cystoscopic evaluation.
Outcome measures
| Measure |
Durvalumab + Tremelimumab
n=32 Participants
Experimental arm:
Durvalumab 1500 mg i.v. plus tremelimumab 75 mg i.v., every 4 weeks for a total of 3 doses Radiotherapy 46 Gy to the minor pelvis and 64-66 Gy to the bladder.
|
|---|---|
|
Rate of Late Salvage Cystectomies
Required late cystectomy
|
2 Participants
|
|
Rate of Late Salvage Cystectomies
Not required late cystectomy
|
30 Participants
|
SECONDARY outcome
Timeframe: 24 monthsTime from the start of immunotherapy to either the date of cystectomy or the date of recurrence of muscle- invasive bladder carcinoma or metastasis. Here we report the estimated rate of patients free of event at 24 months after the start of immunotherapy. Estimation by kaplan meier method.
Outcome measures
| Measure |
Durvalumab + Tremelimumab
n=32 Participants
Experimental arm:
Durvalumab 1500 mg i.v. plus tremelimumab 75 mg i.v., every 4 weeks for a total of 3 doses Radiotherapy 46 Gy to the minor pelvis and 64-66 Gy to the bladder.
|
|---|---|
|
Survival With Bladder Preserved Free of Tumor
|
65 percentage of patients (%) free of event
Interval 50.3 to 84.1
|
SECONDARY outcome
Timeframe: 24 monthsTime from treatment start to tumour relapse or distant progression (without Salvage cystectomy). Bladder relapse with salvage cystectomy is not considered as an event. Deaths are also considered as events. Here we report the estimated rate of patients free of events at 24 months after the start of the immunotherapy. Estimation by kaplan meier method.
Outcome measures
| Measure |
Durvalumab + Tremelimumab
n=32 Participants
Experimental arm:
Durvalumab 1500 mg i.v. plus tremelimumab 75 mg i.v., every 4 weeks for a total of 3 doses Radiotherapy 46 Gy to the minor pelvis and 64-66 Gy to the bladder.
|
|---|---|
|
Disease-free Survival
|
71.4 percentage of patients (%) free of event
Interval 57.2 to 89.1
|
SECONDARY outcome
Timeframe: 24 monthsTime from the start of immunotherapy to the date of death due to any cause. The reported outcome is the estimated ratio of patients alive at 24 months after start of immunotherapy using kaplan meier method.
Outcome measures
| Measure |
Durvalumab + Tremelimumab
n=32 Participants
Experimental arm:
Durvalumab 1500 mg i.v. plus tremelimumab 75 mg i.v., every 4 weeks for a total of 3 doses Radiotherapy 46 Gy to the minor pelvis and 64-66 Gy to the bladder.
|
|---|---|
|
Overall Survival
|
84.3 percentage of patients (%) alive
Interval 72.5 to 97.9
|
SECONDARY outcome
Timeframe: 24 monthsFrequency, nature and number of patients developing adverse events throughout follow up
Outcome measures
| Measure |
Durvalumab + Tremelimumab
n=32 Participants
Experimental arm:
Durvalumab 1500 mg i.v. plus tremelimumab 75 mg i.v., every 4 weeks for a total of 3 doses Radiotherapy 46 Gy to the minor pelvis and 64-66 Gy to the bladder.
|
|---|---|
|
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
Treatment related adverse events of any grade · Had treatment-related adverse events
|
31 Participants
|
|
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
Treatment related adverse events of any grade · Had not treatment-related adverse events
|
1 Participants
|
|
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
Treatment related adverse events Grade ≥3 · Had treatment-related adverse events
|
10 Participants
|
|
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
Treatment related adverse events Grade ≥3 · Had not treatment-related adverse events
|
22 Participants
|
Adverse Events
Durvalumab + Tremelimumab
Serious events: 11 serious events
Other events: 32 other events
Deaths: 7 deaths
Serious adverse events
| Measure |
Durvalumab + Tremelimumab
n=32 participants at risk
The treatment consisted of initial TUR of the tumor, with multiple random biopsies of normal-appearing bladder urothelium, followed by durvalumab 1500 mg i.v. plus tremelimumab 75 mg i.v., every 4 weeks for a total of 3 doses.
Durvalumab: All patients will receive durvalumab (MEDI4736) (1500mg Q4W) in combination with tremelimumab (75 mg IV Q4W) for up to 3 doses/cycles each, unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. If a patient's weight falls to 30kg or below the patient should receive weight-based dosing equivalent to 20 mg/kg of durvalumab Q4W and 1mg/kg tremelimumab Q4W until the weight improves to \>30 kg, at which point the patient should start receiving the fixed dosing of durvalumab 1500mg plus tremelimumab 75 mg Q4W.
Tremelimumab: All patients will receive durvalumab (MEDI4736) (1500mg Q4W) in combination with tremelimumab (75 mg IV Q4W) for up to 3 doses/cycles each, unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. If a patient's weight falls to 30kg or below the patient should receive weight-based dosing equivalent to 20 mg/kg of durvalumab Q4W and 1mg/kg tremelimumab Q4W until the weight improves to \>30 kg, at which point the patient should start receiving the fixed dosing of durvalumab 1500mg plus tremelimumab 75 mg Q4W.
Radiotherapy 46 Gy to the minor pelvis and 64-66 Gy to the bladder.
|
|---|---|
|
General disorders
Fever
|
9.4%
3/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Gastrointestinal disorders
Immunomediated colitis
|
6.2%
2/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Gastrointestinal disorders
Diarrhea
|
15.6%
5/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Renal and urinary disorders
Acute kidney injury
|
6.2%
2/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Renal and urinary disorders
Urinary tract infection
|
3.1%
1/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, specify -
|
6.2%
2/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Renal and urinary disorders
Acute pyelonephritis
|
3.1%
1/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Blood and lymphatic system disorders
Platelet count decreased
|
3.1%
1/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Infections and infestations
Infections and infestations - Other, specify
|
6.2%
2/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Vascular disorders
Hypotension
|
3.1%
1/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
General disorders
General disorders and administration site conditions - Other, specify
|
3.1%
1/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Gastrointestinal disorders
Fecaloid peritonitis
|
3.1%
1/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Renal and urinary disorders
Cystitis noninfective
|
3.1%
1/32 • Throughout the study period, approximately a median o 24 months follow up.
|
Other adverse events
| Measure |
Durvalumab + Tremelimumab
n=32 participants at risk
The treatment consisted of initial TUR of the tumor, with multiple random biopsies of normal-appearing bladder urothelium, followed by durvalumab 1500 mg i.v. plus tremelimumab 75 mg i.v., every 4 weeks for a total of 3 doses.
Durvalumab: All patients will receive durvalumab (MEDI4736) (1500mg Q4W) in combination with tremelimumab (75 mg IV Q4W) for up to 3 doses/cycles each, unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. If a patient's weight falls to 30kg or below the patient should receive weight-based dosing equivalent to 20 mg/kg of durvalumab Q4W and 1mg/kg tremelimumab Q4W until the weight improves to \>30 kg, at which point the patient should start receiving the fixed dosing of durvalumab 1500mg plus tremelimumab 75 mg Q4W.
Tremelimumab: All patients will receive durvalumab (MEDI4736) (1500mg Q4W) in combination with tremelimumab (75 mg IV Q4W) for up to 3 doses/cycles each, unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. If a patient's weight falls to 30kg or below the patient should receive weight-based dosing equivalent to 20 mg/kg of durvalumab Q4W and 1mg/kg tremelimumab Q4W until the weight improves to \>30 kg, at which point the patient should start receiving the fixed dosing of durvalumab 1500mg plus tremelimumab 75 mg Q4W.
Radiotherapy 46 Gy to the minor pelvis and 64-66 Gy to the bladder.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
12.5%
4/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, specify
|
15.6%
5/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Investigations
Alanine aminotransferase increased
|
15.6%
5/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Renal and urinary disorders
Urinary tract pain
|
12.5%
4/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Gastrointestinal disorders
Vomiting
|
9.4%
3/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
9.4%
3/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Gastrointestinal disorders
Nausea
|
9.4%
3/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders - Other, specify
|
9.4%
3/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
General disorders
Insomnia
|
9.4%
3/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
General disorders
Edema limbs
|
9.4%
3/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Nervous system disorders
Dizziness
|
9.4%
3/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Gastrointestinal disorders
Constipation
|
9.4%
3/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other, specify
|
12.5%
4/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Metabolism and nutrition disorders
Hypothyroidism
|
12.5%
4/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Blood and lymphatic system disorders
Hematuria
|
12.5%
4/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
General disorders
General disorders and administration site conditions - Other, specify
|
9.4%
3/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Investigations
Aspartate aminotransferase increased
|
12.5%
4/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Metabolism and nutrition disorders
Anorexia
|
12.5%
4/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Renal and urinary disorders
Renal and urinary disorders - Other, specify
|
46.9%
15/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Gastrointestinal disorders
Diarrhea
|
28.1%
9/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Renal and urinary disorders
Urinary frequency
|
34.4%
11/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Metabolism and nutrition disorders
Hyperthyroidism
|
25.0%
8/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
21.9%
7/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, specify
|
21.9%
7/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
General disorders
Fatigue
|
21.9%
7/32 • Throughout the study period, approximately a median o 24 months follow up.
|
|
Renal and urinary disorders
Urinary tract infection
|
15.6%
5/32 • Throughout the study period, approximately a median o 24 months follow up.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place