CheckMate 274

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bristol-Myers Squibb Services Unlimited Company

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

6 May 2016 → ongoing

Decision date (initial)

2022-08-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Bristol-Myers Squibb International Corporation

External identifiers

EU CT number

2022-500630-29-00

EudraCT number

2014-003626-40

WHO UTN

U1111-1160-7285

ClinicalTrials.gov

NCT02632409

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Pharmacokinetic, Therapy, Safety, Pharmacodynamic, Prophylaxis, Efficacy, Others

To compare the disease free survival (DFS) for nivolumab versus placebo in subjects with tumors expressing PD-L1 (>=1% membranous staining in tumor cells) and all randomized subjects

Secondary objectives 3

1. To compare the overall survival (OS) for nivolumab versus placebo in subjects with tumors expressing PD-L1 (>= 1% membranous staining in tumor cells) and all randomized subjects
2. To evaluate non-urothelial tract recurrence free survival (NUTRFS) in each randomized treatment group (nivolumab versus placebo) in subjects with tumors expressing PD-L1 (>= 1% membranous staining in tumor cells) and all randomized subjects
3. To evaluate disease specific survival (DSS) in each randomized treatment group (nivolumab and placebo) in subjects with tumors expressing PD-L1 (>= 1% membranous staining in tumor cells) and all randomized subjects

Conditions and MedDRA coding

Subjects with High Risk Invasive Urothelial Carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. All subjects must be status post radical surgical resection (R0) for Invasive Urothelial Carcinoma performed within 120 days prior to randomization. Subjects with carcinoma in situ in surgical margins are not eligible for study entry.
2. All subjects must have pathologic evidence of urothelial carcinoma (originating in bladder, ureter, or renal pelvis) at high risk of recurrence based on pathologic staging of radical surgery tissue (see protocol for more details)
3. Dominant component of histology needs to be urothelial carcinoma or transitional cell carcinoma. Foci of varied histologies (eg. minor variants) are accepted
4. All subjects must have disease-free status defined as no clinical or radiographic evidence of recurrence of disease documented by a complete physical examination and imaging studies within 4 weeks of randomization. Subjects with equivocal nodes less than 15 mm in short axis may be eligible after discussion with BMS Medical Monitor. Imaging studies must include CT of chest and CT or MRI of abdomen, pelvis, and all known sites of resected disease including cystoscopy in subjects with upper GU primaries who still have bladder intact. Brain imaging (MRI except where contraindicated in which CT scan is acceptable) must be completed within 4 weeks prior to randomization for subjects with clinical suspicion of CNS disease. Subjects who are found to have high-risk NMIBC at the time of screening are not eligible for study entry. Patients with low-risk papillary lesions may enter the study if rendered free of disease at cystoscopy. Subjects with intermediate-risk NMIBC may enter the study if intravesical chemotherapy or BCG is not required. Screening cystoscopy may occur within 60 days of randomization and is encouraged to be done prior to other imaging. Any suspect lesions seen on cystoscopy should be biopsied to rule-out the possibility of high-risk lesions
5. Tumor tissue from the most recently resected site of disease (preferable) or from the transurethral resection that yielded the initial muscle invasive diagnosis must be provided for biomarker analyses. In order to be randomized, a subject must have a PD-L1 expression level classification (>=1%, < 1%, indeterminate) as determined by the central lab.
6. Life expectancy >= 6 months
7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. Subjects who have not received cisplatin based neoadjuvant chemotherapy and are considered ineligible for cisplatin adjuvant chemotherapy, may enter the study with ECOG PS 2
8. Prior surgery that required general anesthesia must be completed at least 4 weeks before study drug administration. Surgery requiring local/epidural anesthesia must be completed at least 72 hours before study drug administration. TURBT must be completed 14 days before randomization

Exclusion criteria 9

1. Partial cystectomy in the setting of bladder cancer primary tumor or partial nephrectomy in the setting of renal pelvis primary tumor
2. Adjuvant systemic or radiation therapy for urothelial or prostatic carcinoma following radical surgical resection of urothelial carcinoma
3. Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results
4. Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, prostate cancer with evidence of undetectable Prostate Specific Antigen (PSA) or carcinoma in situ of the prostate, cervix or breast. Patients with known history of recent metastatic urothelial carcinoma will be excluded.
5. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enrol
6. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
7. Subjects with history of life-threatening toxicity related to prior immune therapy (eg. anti-CTLA-4 or anti-PD-1/PD-L1 treatment or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) except those that are unlikely to re-occur with standard countermeasures (eg, hormone replacement after adrenal crisis)
8. All toxicities attributed to prior anti-cancer therapy other than nephropathy, neuropathy, hearing loss, alopecia and fatigue must have resolved to Grade 1 (NCI CTCAE version 4) or baseline before administration of study drug. Subjects with toxicities attributed to prior anti-cancer therapy which are not expected to resolve and result in long lasting sequelae, such as neuropathy after platinum based therapy, are permitted to enroll. See protocol inclusion criterion 2) i) (5) for renal function eligibility. Neuropathy must have resolved to Grade 2 (NCI CTCAE version 4)
9. Treatment with any chemotherapy, radiation therapy, biologics for cancer, intravesical therapy, or investigational therapy within 28 days of first administration of study treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease Free Survival - This endpoint will be analyzed in two different populations (co-primary): Subjects with PD-L1 expression level >=1% and all randomized subjects

Secondary endpoints 3

1. To compare Non-Urothelial Tract Recurrence Free Survival (NUTRFS) for nivolumab versus placebo in subjects with tumors expressing PD-L1 (>= 1% membranous staining in tumor cells) and all randomized subjects
2. To compare the Disease Specific Survival (DSS) for nivolumab and placebo in subjects with tumors expressing PD-L1 (>=1% membranous staining in tumor cells) and all randomized subjects
3. To compare the Overall Survival (OS) for nivolumab versus placebo in subjects with tumors expressing PD-L1 (>=1% membranous staining in tumor cells) and all randomized subjects

Investigational products

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

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bristol-Myers Squibb Services Unlimited Company

Sponsor organisation

Bristol-Myers Squibb Services Unlimited Company

Address

Plaza 254, Blanchardstown Corporate Park 2 Blanchardstown Corporate Park 2

City

Dublin 15

Postcode

D15 T867

Country

Ireland

Scientific contact point

Organisation

Bristol-Myers Squibb International Corporation

Contact name

GSM-CT

Public contact point

Organisation

Bristol-Myers Squibb International Corporation

Contact name

GSM-CT

Third parties 9

Locations

13 EU/EEA countries · 40 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 93 files

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

Application history

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