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Bladder CancerPhase 2ABACUSNCT02662309

Preoperative MPDL3280A in Transitional Cell Carcinoma of the Bladder

A Phase 2 study testing MPDL3280A in people with Bladder Cancer, run by Queen Mary University of London at 20 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

ABACUS is an open-label, international, multi-centre, window of opportunity phase II trial for patients with histologically confirmed (T2-T4a) transitional cell carcinoma of the bladder. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Bladder Cancer
What is being tested?
MPDL3280A
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
96 participants
Where
20 sitesin 4 countries
Study dates
1 Feb 2016to 11 Jun 2020
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Willing and able to provide written informed consent
  • Ability to comply with the protocol
  • Age ≥ 18 years
  • Histopathologically confirmed transitional cell carcinoma (T2-T4a) of the bladder. Patients with mixed histologies are required to have a dominant transitional cell pattern.
  • Residual disease after TURBT (surgical opinion, cystoscopy or radiological presence).
  • Fit and planned for cystectomy (according to local guidelines).
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  • N0 or M0 disease CT or MRI (within 4 weeks of registration)
  • Representative formalin-fixed paraffin embedded (FFPE) bladder tumour samples with an associated pathology report that are determined to be available and sufficient for central testing.
  • Patients who refuse neoadjuvant cisplatin based chemotherapy or in whom neoadjuvant cisplatin based therapy is not appropriate.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Negative pregnancy test within 2 weeks of Day 1 Cycle 1 for female patients of childbearing potential.
  • For female patients of childbearing potential to use a highly effecting form(s) of contraception (i.e. one that results in a low failure rate [<1% per year] when used consistently and correctly) and to continue its use for 90 days after the last dose of MPDL3280A.
  • Adequate hematologic and end-organ function within 4 weeks prior to the first study treatment

Who cannot join

  • 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 bladder 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.
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  • 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 UBC 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).
  • Patients with uncontrolled Type 1 diabetes mellitus. Patients with Type 1 diabetes controlled on a stable insulin regimen are eligible.
  • Patients with active hepatitis infection (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
  • Positive test for HIV
  • Patients with active tuberculosis
  • History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug.
  • Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or Ca > 12 mg/dL or corrected serum calcium > the institutional ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab. Patients who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible. Patients who are receiving denosumab prior to enrollment must be willing and eligible to receive a bisphosphonate instead while on study.
  • History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
  • Patients with a history of autoimmune-related hypothyroidism, unless on a stable dose of thyroid-replacement hormone.
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the MPDL3280A formulation

Trial locations and contacts

20 sites in 4 countries.

20 sites in 4 countries

Spain9 sites

  • Athaia Xarxa Manresa

    Barcelona

  • Hospital del Mar

    Barcelona

  • Hospital Germans Trias i Pujol

    Barcelona

  • Hospital Santa Creu i Sant Pau

    Barcelona

  • Hospital Vall d'Hebron

    Barcelona

  • Hospital Reina Sofía

    Córdoba

  • Hospital 12 de Octubre

    Madrid

  • CHU de Santiago

    Santiago de Compostela

  • Hospital Virgen del Rocío

    Seville

Other trials in Spain

United Kingdom6 sites

  • Clatterbridge Cancer Centre NHS Foundation Trust

    Liverpool

  • Barts Health NHS Trust

    London

  • University College London Hospitals NHS Foundation Trust

    London

  • Oxford University Hospitals NHS Foundation Trust

    Oxford

  • Sheffield Teaching Hospitals NHS Foundation Trust

    Sheffield

  • University Hospital Southampton NHS Foundation Trust

    Southampton

Other trials in United Kingdom

France4 sites

  • Centre Hospitalier Universitaire (CHU) de Bordeaux

    Bordeaux

  • Hospices Civils de Lyon

    Lyon

  • Institut Paoli-Calmettes

    Marseille

  • Institut Claudius Régaud

    Toulouse

Other trials in France

Netherlands1 site

  • Netherlands Cancer Institute (NKI)

    Amsterdam

Other trials in Netherlands

About this study

Official title: A Phase II Study Investigating Preoperative MPDL3280A in Operable Transitional Cell Carcinoma of the Bladder (ABACUS)

ABACUS is an open-label, international, multi-centre, window of opportunity phase II trial for patients with histologically confirmed (T2-T4a) transitional cell carcinoma of the bladder. The trial aims to test the efficacy of preoperative MPDL3280A and will include extensive biomarker work on samples from these patients. Eligible patients will receive two 3-weekly cycles of MPDL3280A pre-cystectomy. Following cystectomy, patients will be followed up for safety, survival, and disease data.

Read the detailed description

MPDL3280A (also called atezolizumab) is an immune check point inhibitor which targets programmed death-ligand 1 (PD-L1). Overexpression of PD-L1 prevents the immune system from eradicating cancerous cells as it blocks antigen recognition. MPDL3280A inhibits this interaction, allowing immune-mediated tumour cell killing.

Conditions
Bladder Cancer
Being tested
MPDL3280A
Keywords
Muscle invasive bladder cancer, Transitional cell carcinoma
Medical subject headings
Urinary Bladder Neoplasms, Carcinoma, Transitional Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MPDL3280ADrug

    Also called Atezolizumab

    Intravenous infusion

Study groups in NCT02662309
Study groupRoleWhat they receive
MPDL3280AExperimentalPatients receive 2x 3-weekly cycles of MPDL3280A (one infusion on the first day of each cycle) prior to cystectomy surgery.
Receives: Drug: MPDL3280A

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Efficacy of MPDL3280A pre-cystectomy with respect to pathological complete response rate (pCRR)

    Pathological complete response rate defined as no microscopic evidence of residual disease in the bladder based on histological evaluation of the resected bladder specimen collected during cystectomy (post-treatment).

    Measured: 2-3 months (timeframe dependent on delay to surgery)

Secondary outcomes (3)

  1. Efficacy of MPDL3280A pre-cystectomy with respect to anti-tumour effects as measured by radiological response (RR)

    CT or MRI scan taken at screening and pre-cystectomy visits. RR is defined as a >30% decrease in tumour diameter from the baseline scan.

    Measured: Approx 34 weeks (timeframe dependent on delay to pre-cystectomy visit)

  2. Efficacy of MPDL3280A pre-cystectomy with respect to anti-tumour effects based on disease free survival (DFS)

    Disease and survival data is reviewed at post-surgery visits and at 1 and 2 years post-cystectomy.

    Measured: Up to 2 years post-cystectomy

  3. Efficacy of MPDL3280A pre-cystectomy with respect to anti-tumour effects based on overall survival (OS)

    Disease and survival data is reviewed at post-surgery visits and at 1 and 2 years post-cystectomy.

    Measured: Up to 2 years post-cystectomy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jan 2016 (estimated)
  2. Study start1 Feb 2016
  3. Primary completion11 Jun 2020
  4. Study completion11 Jun 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
96 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02662309
Sponsor's protocol ID
010463QM
Other IDs
2015-001112-35, 2015
Acronym
ABACUS
Status last verified
Mar 2025
First submitted
18 Jan 2016
Last updated
10 Mar 2025
Results posted
No
Data monitoring committee
Yes

Publications

  • Powles, T., et al., A phase II study investigating the safety and efficacy of neoadjuvant atezolizumab in muscle invasive bladder cancer (ABACUS). Journal of Clinical Oncology, 2018. 36(15_suppl): p. 4506-4506.

  • Powles T, Kockx M, Rodriguez-Vida A, Duran I, Crabb SJ, Van Der Heijden MS, Szabados B, Pous AF, Gravis G, Herranz UA, Protheroe A, Ravaud A, Maillet D, Mendez MJ, Suarez C, Linch M, Prendergast A, van Dam PJ, Stanoeva D, Daelemans S, Mariathasan S, Tea JS, Mousa K, Banchereau R, Castellano D. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial. Nat Med. 2019 Nov;25(11):1706-1714. doi: 10.1038/s41591-019-0628-7. Epub 2019 Nov 4.

    PubMed 31686036

  • Elias R, Aragaki AK, Hoffman-Censits JH, Hahn NM, McConkey DJ, Johnson BA 3rd. Intratumoral Expression of a Composite B Cell / CD8 T Cell Biomarker Stratifies Overall Survival by Circulating Tumor DNA Status and Benefit From Adjuvant Immunotherapy in High-Risk Muscle-Invasive Urothelial Carcinoma. J Urol. 2026 Mar;215(3):294-304. doi: 10.1097/JU.0000000000004828. Epub 2025 Oct 27.

    PubMed 41144872

  • Szabados B, Rodriguez-Vida A, Duran I, Crabb SJ, Van Der Heijden MS, Pous AF, Gravis G, Herranz UA, Protheroe A, Ravaud A, Maillet D, Mendez-Vidal MJ, Suarez C, Linch M, Prendergast A, Tyson C, Mousa K, Castellano D, Powles T. Toxicity and Surgical Complication Rates of Neoadjuvant Atezolizumab in Patients with Muscle-invasive Bladder Cancer Undergoing Radical Cystectomy: Updated Safety Results from the ABACUS Trial. Eur Urol Oncol. 2021 Jun;4(3):456-463. doi: 10.1016/j.euo.2020.11.010. Epub 2021 Feb 18.

    PubMed 33612455

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MPDL3280A in people with Bladder Cancer, run by Queen Mary University of London at 20 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Spain, United Kingdom, France, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy of MPDL3280A pre-cystectomy with respect to pathological complete response rate (pCRR) (time frame: 2-3 months (timeframe dependent on delay to surgery)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02662309, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2025.

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