DURvalumab in Combination With S-488210/S-488211 vAccine in Non-muscle Invasive Bladder CancEr

NCT04106115 | Recruiting Phase 1 DMC

• 1 other identifier: UCL/121881
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 5

Brief Summary

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).

Conditions

Bladder Cancer

Keywords

Non-Muscle Invasive Bladder Cancer (NMIBC); Durvalumab; S-488210/S-488211; Immunotherapy; Vaccine; PD-L1 Inhibitor; BCG unresponsive

Outcome Measures

Primary Outcomes (2)

• 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).

  At the end of cycle 1 (cycle 1 is 28 days)

• Pathological Disease Free Survival Rate (DFSR) (Phase 2)

  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 after start of treatment

Secondary Outcomes (6)

• 1 year DFSR stratified by HLA-A*02:01

  1 year after start of treatment

• 5 year Overall Survival rate

  5 years from start of treatment to date of death, if applicable.

• 5 year Overall Survival rate stratified by HLA-A*02:01

  5 years from start of treatment to date of death, if applicable.

• Assessment of Quality of Life using EORTC QLQ-C30 questionnaire

  Assessments will be performed at baseline (prior to starting treatment on cycle 1 days 1), every 12 weeks up to 12 months after start of treatment and 24 months after start of treatment.

• Assessment of Quality of Life using EORTC QLQ-NMIBC24 questions

  Assessments will be performed at baseline (prior to starting treatment on cycle 1 days 1), every 12 weeks up to 12 months after start of treatment and 24 months after start of treatment.

Other Outcomes (4)

• 1 year DFSR stratified by PD-L1 status

  1 year after start of treatment

• 1 year DFSR stratified by baseline Tumour Infiltrating Lymphocyte (TIL) status

  1 year after start of treatment

• 5 year Overall Survival rate stratified by PD-L1 status and TIL status

  5 years from start of treatment to date of death, if applicable.

Study Arms (1)

Durvalumab + S-488210/S-488211

EXPERIMENTAL

Trial treatment for up to 24 weeks of Durvalumab (1500 mg IV infusion every 4 weeks for up to 7 doses) in combination with S-488210/S-488211 vaccine (given as 2 subcutaneous injections of S-488210/Montanide and S-488211/Montanide starting day after first durvalumab dose, then weekly for the first 6 weeks, and then every 2 weeks for a further 9 doses).

Drug: Durvalumab; Biological: S-488210/S-488211

Interventions

Durvalumab DRUG

1500 mg IV infusion every 4 weeks for up to 7 doses

Also known as: MEDI 4736

Durvalumab + S-488210/S-488211

S-488210/S-488211 BIOLOGICAL

S-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

Also known as: S-488210/Montanide, S-488211/Montanide

Durvalumab + S-488210/S-488211

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Refused or deemed clinically inappropriate for radical cystectomy
• ≥18 years of age
• Body weight \>30 kg
• World Health Organisation (WHO) performance status 0-1
• Must have undergone each of the following procedures within 8 weeks of registration:
• Complete excision of all papillary disease (T1/TaHG) and demonstration of no muscle invasive disease in the resected specimens (muscle must be present in the tumour sample)
• Bladder 'Mapping biopsies' taken
• CT of the chest
• CT Urogram or MRI of the abdomen and pelvis (if CT is not possible)
• Adequate haematological status:
• Haemoglobin ≥9.0 g/dL

You may not qualify if:

• Any history of autoimmune or inflammatory disease including (any patients with a history of an autoimmune condition but without active disease in the last 5 years may be included only after consultation with the CI/TMG):
• Inflammatory bowel disease (e.g. colitis or Crohn's disease)
• Diverticulitis (with the exception of diverticulosis)
• Systemic lupus erythematous (SLE)
• Sarcoidosis syndrome
• Wegener syndrome (granulomatosis with polyangitis, Grave's disease, rheumatoid arthritis, hypophysitis, uveitis, etc.)
• Patients with prior allogeneic stem cell or solid organ transplantation
• Patients who have had prior treatment with anti- PD-1, PD-L1 or CTLA-4 monoclonal antibody or other novel immune-oncology agent(s)
• Active invasive malignancy in the previous 2 years excluding non-melanoma skin cancer
• History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia) or evidence of active pneumonitis on screening chest CT scan (history of radiation pneumonitis in the radiation field is permitted)
• Patients with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
• QTcF value of \>470 ms. If prolonged, this should be confirmed by 2 further ECGs each separated by at least 5 minutes.
• Patients with the following risk factors for bowel perforation:
• History of acute diverticulitis or intra-abdominal abcess in the last 3 years
• History of mechanical GI obstruction or abdominal carcinomatosis

Sponsors & Collaborators

• University College, London: lead
• AstraZeneca: collaborator
• Shionogi: collaborator

Study Sites (5)

Guy's and St Thomas' NHS Foundation Trust

London, United Kingdom

RECRUITING

The Royal Marsden NHS Foundation Trust

London, United Kingdom

RECRUITING

University College London Hospital NHS Foundation Trust

London, United Kingdom

RECRUITING

The Christie NHS Foundation Trust

Manchester, United Kingdom

RECRUITING

University Hospital Southampton NHS Foundation Trust

Southampton, United Kingdom

RECRUITING

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms

Interventions

durvalumab; Monatide (IMS 3015)

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Mark Linch

  University College London Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Madison Williams

CONTACT

02076799514; ctc.durance@ucl.ac.uk

Rubina Begum

CONTACT

02076799514; rubina.begum@ucl.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2019
• First Posted: September 26, 2019
• Study Start: March 25, 2022
• Primary Completion: May 31, 2025
• Study Completion (Estimated): May 31, 2029
• Last Updated: December 4, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (5)