DURANCE is a two part, phase Ib/II, multi-centre study to assess the safety and activity of S-488210/S-488211 in combination with durvalumab, in patients with non-muscle invasive bladder cancer (NMIBC).
Histologically proven high risk non-muscle invasive bladder cancer (NMIBC)
Adequate archival tissue sample available for histological assessment (date sample taken must be within 6 months of planned start of treatment)
Predominant histologic component (> 50%) must be urothelial (transitional cell) carcinoma
Bacillus Calmette-Guerin (BCG) unresponsive disease or are intolerant of BCG therapy
Inflammatory bowel disease (e.g. colitis or Crohn's disease)
Diverticulitis (with the exception of diverticulosis)
Systemic lupus erythematous (SLE)
Sarcoidosis syndrome
Single group
Durvalumab
Drug1500 mg IV infusion every 4 weeks for up to 7 doses
S-488210/S-488211
Biological/VaccineS-488210/S-488211 is given as a 1 mL subcutaneous (SC) injection of S-488210/Montanide emulsion and a 1 mL SC injection of S-488211/Montanide emulsion starting the day after first dose of durvalumab and continuing weekly for 6 doses and then every 2 weeks for a further 9 doses
Occurrence of Dose Limiting Toxicity (Phase 1b)
Detailed adverse event monitoring will be conducted, assessed using CTCAE v5. Dose Limiting Toxicity (DLT) is defined as any adverse event or laboratory abnormality detailed in the trial protocol, that has a reasonable possibility of being related to trial treatment and occurring at anytime during the DLT evaluation period (28 days from the first administration of S-488210/S-488211 on cycle 1 day 2).
Pathological Disease Free Survival Rate (DFSR) (Phase 2) from cystoscopy and mapping biopsies
Disease Free Survival will be calculated from start of trial treatment (cycle 1 day 1) until the time at which either primary disease is confirmed to have recurred, any secondary cancer is confirmed or death from any cause. The primary endpoint of Disease Free Survival Rate will be assessed at 1 year from start of treatment (and include patients that start trial treatment and receive combination treatment on cycle 2 day 1) and compared to the historical control rate of 20%.
1 year DFSR stratified by HLA-A*02:01
If the primary endpoint (DFSR) is statistically signification, comparison of DFSR at 1 year will be conducted between patients that are human leukocyte antigen-A (HLA-A\*02:01) positive versus negative.
Overall Survival rate
Overall survival will be assessed from time of starting treatment to time of death from any cause.
5 year Overall Survival rate stratified by HLA-A*02:01
Overall survival will be assessed from time of starting treatment to time of death from any cause, stratified by HLA-A\*02:01 positive or negative.
Assessment of Quality of Life using EORTC QLQ-C30 questionnaire
Quality of Life assessments will be undertaken using EORTC QLQ-C30 (version 3) questionnaire using Likert score (26 questions scored: 1=not at all, 2=a little, 3=quite a bit, 4=very much; 2 questions scored: 1-7, 1=very poor, 7=excellent) . Descriptions of mean change in EORTC QLQ scores will be presented and compared to baseline values from pre-treatment.
DFSR stratified by PD-L1 status
DFSR stratified, retrospectively, by PD-L1 status will be performed.
DFSR stratified by baseline Tumour Infiltrating Lymphocyte (TIL) status
DFSR stratified, retrospectively, by TIL status (high, intermediate and low) to assess the distribution of a three-category variable (TIL status) over survival status.
Overall Survival rate stratified by PD-L1 status and TIL status
Overall survival will be assessed from time of starting treatment to time of death from any cause, stratified by PD-L1 status and TIL status.
Correlation of plasma cytokine levels with 1 year DFSR
The association between DFSR at 1 year and plasma cytokine levels will be assessed using logistic regression, with odds ratios and 95% confidence interval reported.
Click on the lead sponsor to view all of their trials.
