Neoadjuvant Immune Checkpoint Inhibitor Treatment in Urothelial Cancer

NCT04624399 | Recruiting Phase 2 DMC

• 1 other identifier: ABACUS-2
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being carried out to see if the drug atezolizumab can reduce the size of tumours in patients with types of urothelial cancer before surgery. Atezolizumab is designed to stop a protein called PD-L1 (programmed death-ligand 1) being expressed on the cancer, allowing the immune system to recognise the tumour cells as foreign bodies and attack them. Atezolizumab has been shown to have activity in urothelial cancer which has spread. There two cohorts for this trial. One cohort will investigate the most common histological type of urothelial cancer (transitional cell carcinoma) outside the bladder, for example in the upper urinary tract. The other cohort will investigate rarer histological subtypes (such as such as squamous cell or adenocarcinoma) of urothelial cancer throughout the entire urinary system. This study will be recruiting patients from hospitals in the UK, France and Spain. If a patient is eligible for the study and decides to take part, they will receive up to two 3-weekly cycles of atezolizumab. 4-8 weeks after being enrolled, the patient will have an operation to remove the bladder (cystectomy) or the kidney, ureter and part of the bladder (nephroureterectomy or distal ureteral resection) as per normal practice. Following surgery, they will attend three hospital visits (4,12 and 24 weeks after surgery) and their disease progress/survival will be followed over the next 2 years. The clinical team will compare the patient's tumour tissue samples,scan results and blood results from before and after treatment with atezolizumab in order to see how well the drug works and if it is safe. Many of the procedures involved in this study are offered as standard care and participation in this trial will not delay surgery.

Conditions

Urogenital Cancer

Outcome Measures

Primary Outcomes (2)

• Pathological complete response rate (pCRR)

  No microscopic evidence (pT0/Tis/Cis) of residual disease in the bladder based on histological evaluation of the resected bladder specimen collected during cystectomy (post-treatment) \[Bladder Cohort\] \- No microscopic evidence (pT0/Tis/Cis) of residual disease in the renal pelvis or ureter in the resected sample collected during radical surgery for upper tract disease (post-treatment) \[UTUC Cohort\]

  At surgery (4-8 weeks after patient registration)

• Assessment on immune parameters

  ynamic changes in T cell subpopulations (CD8 and/or CD3) measured in tumour samples collected pre- and post-treatment.

  Samples acquired at surgery (4-8 weeks after patient registration)

Secondary Outcomes (4)

• Evaluate the safety and tolerability of atezolizumab when given in the neoadjuvant setting

  Adverse Events will be collated during treatment and up to 24 weeks post-cystectomy or post-radical surgery. Surgical complications will be assessed at the 4wk and 12 week follow-up visits.

• Assess the efficacy of atezolizumab given in the neoadjuvant setting with respect to anti-tumour effects as measured by Investigator assessed radiological response (RR)

  Assessed at CT scan pre-surgery.

• Assess the efficacy of atezolizumab given in the neoadjuvant setting with respect to anti-tumour effects based on Investigator assessed disease-free survival (DFS)

  Evaluated at 12 weeks, 24 weeks, 12 months, and 24 months post-surgery.

• Assess the efficacy of atezolizumab given in the neoadjuvant setting with respect to overall survival (OS)

  Evaluated at 12 weeks, 24 weeks, 12 months, and 24 months post-surgery.

Study Arms (1)

Atezolizumab

EXPERIMENTAL

Patients receive 2 x 3-weekly cycles of Atezolizumab (one infusion on the first day of each cycle) prior to cystectomy surgery.

Drug: Atezolizumab

Interventions

Atezolizumab DRUG

Patients receive 2 x 3-weekly cycles of Atezolizumab (one infusion on the first day of each cycle) prior to cystectomy surgery.

Also known as: MPDL3280A

Atezolizumab

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• UTUC cohort:
• Histopathologically confirmed,high grade or high risk upper urinary tract urothelial carcinoma (renal pelvis and ureter). This cohort includes all patients with upper tract malignancy who in the opinion of the investigators qualify for radical surgery (nephroureterectomy or distal ureter resection). Urothelial carcinoma of the upper urinary tract qualifies as high-risk disease if any of the below factors are present:
• Hydronephrosis
• Tumour size \>2cm on cross sectional imaging
• High grade cytology
• High grade biopsy
• Multifocal disease
• Variant histology
• Previous radical cystectomy for urothelial cancer of the bladder
• All patients undergoing radical surgery with curative intent in the opinion of the investigator are eligible. Radical surgical interventions include nephroureterectomy or distal ureteral resection.
• Willing and able to provide written informed consent
• Ability to comply with the protocol
• Age ≥ 18 years
• Residual disease after TURBT or URS (surgical opinion, endoscopy or radiological presence).
• Fit and planned for radical surgery with curative intent in the opinion of the investigator (according to local guidelines).

You may not qualify if:

• Pregnant and lactating female patients.
• Major surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.
• Previously intravenous chemotherapy for urothelial cancer.
• Patients with prior allogeneic stem cell or solid organ transplantation.
• Prior treatment with CD137 agonists,anti-CTLA-4,anti-programmed death-1 (PD-1),or anti-PD-L1 therapeutic antibody or pathway-targeting agents.
• Patients must not have had oral or IV steroids for 14 days prior to study entry. The use of inhaled corticosteroids, physiologic replacement doses of glucocorticoids (i.e.,for adrenal insufficiency), and mineralocorticoids (e.g. fludrocortisone) is allowed.
• Received therapeutic oral or intravenous (IV) antibiotics within 14 days prior to enrolment (Patients receiving prophylactic antibiotics (e.g.,for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible).
• Administration of a live,attenuated vaccine within 4 weeks prior to enrolment or anticipation that such a live,attenuated vaccine will be required during the study.
• Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin \[IL\]-2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment.
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 4 weeks prior to enrolment.
• Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome).
• Malignancies other than UC within 5 years prior to Cycle 1,Day 1,with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer (Gleason score ≤ 3 + 4 and PSA \< 10 ng/mL undergoing active surveillance and treatment naive).
• Severe infections within 4 weeks prior to enrolment in the study including but not limited to hospitalization for complications of infection, bacteraemia,or severe pneumonia.
• Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to enrolment, unstable arrhythmias, or unstable angina.
• 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 (fibrosis) is permitted).

Sponsors & Collaborators

• Queen Mary University of London: lead
• Hoffmann-La Roche: collaborator

Study Sites (1)

Barts and London Hospital NHS Trust

London, United Kingdom

RECRUITING

MeSH Terms

Conditions

Urogenital Neoplasms

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Thomas Powles

  Queen Mary University of London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

ABACUS-2 Trial Coordinator

CONTACT

020 7882 8478; bci-abacus2@qmul.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2020
• First Posted: November 10, 2020
• Study Start: June 17, 2021
• Primary Completion (Estimated): May 30, 2026
• Study Completion (Estimated): May 30, 2026
• Last Updated: November 18, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)