Study to evaluate the efficacy and safety of Durvalumab(MEDI4736) in combination with intravesical BCG for the treatment of patients diagnosed with early stage bladder cancer (non-muscle invasive) compared to the standard therapy of intravesical BCG alone.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Healthy volunteers, Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 Jul 2018 → ongoing

Decision date (initial)

2024-03-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB Sweden

External identifiers

EU CT number

2023-505341-23-00

EudraCT number

2017-002979-26

ClinicalTrials.gov

NCT03528694

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis

To assess the efficacy of durvalumab + BCG combinationtherapy compared to BCG alone in terms of Disease FreeSurvival (DFS).

Secondary objectives 1

1. To assess the efficacy of the combination therapy(Durvalumab plus BCG) compared to SoC in terms of disease free at 24 months (DFS24), overall survival at 5years (OS5), any disease-free survival (aDFS), time to muscle-invasive bladder cancer or metastatic disease, time to cystectomy and time to development of uppertrack urothelial carcinoma. To assess the efficacy of the combination therapy(Durvalumab plus BCG) compared to SoC for patients withCIS prior to study entry or at baseline in terms ofComplete response rate (CRR) at 6 month. To assess disease-related symptoms and HRQoL inpatients treated with durvalumab plus BCG combinationtherapy compared to SoC using EORTC QLQ-C30 andEORTC QLQ NMIBC24. Tolerability using patient-reported PRO CTCAE symptoms. To assess PK of durvalumab and Immunogenicity ofdurvalumab

Conditions and MedDRA coding

Non-muscle invasive bladder cancer

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. -BCG-naïve (patients who have not received priorintravesical BCG or who previously received but stoppedBCG more than 3 years before study entry are eligible). - Local histological confirmation (based on pathologyreport) of high-risk transitional cell carcinoma of theurothelium of the urinary bladder confined to the mucosaor submucosa.A high-risk tumor is defined as one of thefollowing: -T1 tumor -High grade/G3 tumor -CIS -Multiple andrecurrent and large (with diameter of largesttumor ≥3cm) tumors (all conditions must be met in this point) -Complete resection of all Ta/T1 papillary disease prior torandomization, with the TURBT removing high-risk NMIBCperformed not more than 4 months before randomizationin the study. Patients with residual CIS after TURBT are eligible. -No prior radiotherapy for bladder cancer. -No prior exposure to immune-mediated therapy of cancerincluding, but not limited to, other anti CTLA-4, anti-PD-1,anti-PD-L1, and anti-programmed cell death ligand 2antibodies. Patients who have been treated with anticancer vaccines will be excluded.

Exclusion criteria 1

1. -Evidence of muscle-invasive, locally advanced,metastatic, and/or extra vesical bladder cancer (ie, T2,T3, T4, and / or stage IV). -Concurrent extravesical (ie, urethra, ureter, or renalpelvis), non-muscle-invasive transitional cell carcinoma of the urothelium. -Previous investigational product (IP) assignment in the present study. -Any concurrent chemotherapy, IP, biologic, or hormonaltherapy for cancer treatment. Concurrent use of hormonaltherapy for noncancer related conditions (eg, hormonereplacement therapy) is acceptable. Chemotherapy for previous instances of NMIBC is acceptable. Patients who have received a single instillation of Mitomycin C orequivalent chemotherapy agent immediately after TURBT can be enrolled in the study. -Active infection including TB, hepatitis B (known positivehepatitis B virus [HBV] surface antigen [HBsAg] result),hepatitis C virus (HCV), or human immunodeficiency virus(HIV [positive HIV] 1/2) antibodies. Patients with a pastor resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) areeligible. Patients positive for hepatitis C antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA). Appropriate TB tests (e.g.skin or interferon gamma tests) should be performed to exclude TB infection requiring treatment. Additional clinical evaluations including clinical history, physical examination, radiographic findings, and other diagnostic procedures and specialist consultations should be performed if necessary. -Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion: Intranasal, inhaled, topical steroids, or local steroidinjections (eg, intra articular injection) Systemic corticosteroids at physiologic doses not toexceed 10 mg/day of prednisone or its equivalent Steroids as premedication for hypersensitivity reactions(eg, computed tomography [CT] scan premedication) -Active or prior documented autoimmune or inflammatorydisorders (including inflammatory bowel disease [eg,colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegenersyndrome [granulomatosis with polyangiitis, Graves’disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion: Patients with vitiligo or alopecia Patients with hypothyroidism (e.g., following Hashimotosyndrome) stable on hormone replacement. Any chronic skin condition that does not requiresystemic therapy Patients without active disease in the last 5 years maybe included but only after consultation with the Study Physician − Patients with celiac disease controlled by diet alone − History of another primary malignancy except for Malignancy treated with curative intent and with noknown active disease ≥ 2 years before the first dose of IPand of low potential risk for recurrence during study period Adequately treated nonmelanoma skin cancer or lentigomaligna without evidence of disease Adequately treated CIS without evidence of disease Prostate cancer (tumor/node/metastasis stage) of stage≤ T2cN0M0 without biochemical recurrence or progression that in the opinion of the Investigator does not require active intervention.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease-free survival (DFS)

Secondary endpoints 1

1. Disease free at 24 months (DFS24) Survival at 5 years (OS5) Complete response rate (CRR) Any disease-free survival (aDFS) Time to muscle-invasive bladder (MIBC) cancer ormetastasis Time to cystectomy. Time to development of upper track urothelial carcinoma(UTUC) Disease related symptoms Patient reported treatment tolerability Assessment of PK of Durvalumab Immunogenicity of Durvalumab (ADA) in combination with BCG

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

7 EU/EEA countries · 61 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 62 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications