A Study of Subcutaneous Nivolumab in Previously Treated Advanced or Metastatic Clear Cell Renal Cell Carcinoma

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

1 Jun 2021 → 5 Dec 2025

Decision date (initial)

2024-08-01

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

2023-503280-42-00

EudraCT number

2020-003655-15

WHO UTN

U1111-1255-9514

ClinicalTrials.gov

NCT04810078

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

To demonstrate PK noninferiority of SC nivolumab vs IV nivolumab administration

Secondary objectives 4

1. 1. To demonstrate the ORR noninferiority of nivolumab SC vs nivolumab IV administration.
2. 2. To evaluate efficacy of nivolumab SC over 12 months.
3. 3. To evaluate PK of nivolumab SC and nivolumab IV administration.
4. 4. To evaluate the safety profile of nivolumab SC and nivolumab IV administration.

Conditions and MedDRA coding

Metastatic Clear Cell Renal Cell Carcinoma

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myer Squibb’s data sharing policy and process can be found at: https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosure-commitment.html

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. * Histological confirmation of renal cell carcinoma (RCC) with a clear cell component, including participants who may also have sarcomatoid features.
2. * Advanced RCC (not amenable to curative surgery or radiation therapy) or metastatic RCC (Stage IV).
3. * Measurable disease as defined by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 criteria within 28 days prior to randomization.
4. * Received no more than 2 prior systemic treatment regimens.
5. * Intolerance or progression on or after the last treatment regimen received and within 6 months prior to randomization.
6. * Karnofsky PS ≥ 70 at screening.
7. * Must agree to follow specific methods of contraception, if applicable.

Exclusion criteria 8

1. * Untreated, symptomatic central nervous system (CNS) metastases.
2. * Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active within 2 years prior to randomization.
3. * Active, known, or suspected autoimmune disease.
4. * Known human immunodeficiency virus (HIV) positive with an acquired immunodeficiency syndrome (AIDS) defining opportunistic infection within the last year, or a current CD4 count < 350 cells/μL. Participants with HIV are eligible if: 1. They have received established antiretroviral therapy (ART) for at least 4 weeks prior to randomization. 2. They continue on ART as clinically indicated while enrolled on study. 3. CD4 counts and viral load are monitored per standard of care by a local healthcare provider. 4. Inclusion of participants with HIV should be based on Investigator clinical judgment in consultation with the Medical Monitor. NOTE: Testing for HIV must be performed at sites where mandated locally. HIV- positive participants must be excluded where mandated locally.
5. * Serious or uncontrolled medical disorders including for example, active severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2) infection within approximately 4 weeks prior to screening. In the case of prior SARS-CoV-2 infection, acute symptoms must have resolved based on investigator clinical judgment and, in consultation with Medical Monitor, there are no sequelae that would place the participant at a higher risk of receiving investigational treatment to be eligible.
6. * Prior treatment with a programmed death receptor-1 (anti-PD-1), programmed death ligand-1 (anti-PD-L1), or cytotoxic T-lymphocyte associated antigen-4 (anti-CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co stimulation or checkpoint pathways.
7. * Treatment with any live attenuated vaccine within 30 days of first study treatment
8. * Other protocol-defined inclusion/exclusion criteria apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Time-averaged serum concentration over 28 days (Cavgd28)
2. Trough serum concentration at steady-state (Cminss)

Secondary endpoints 33

1. - Objective response rate (ORR) by Blinded Independent Central Review (BICR) with a minimum of 6 months follow-up [ Time Frame: Up to 2 years 6 months ]
2. - Trough serum concentration at day 28 (Cmind28) [ Time Frame: At 28 days ]
3. - Maximum serum concentration after the first dose (Cmax1) [ Time Frame: Up to 7 days ]
4. - Peak serum concentration at steady-state (Cmaxss) [ Time Frame: Up to 4 months ]
5. - Steady-state average serum concentration (Cavgss) [ Time Frame: Up to 4 months ]
6. - Observed trough nivolumab serum concentration (Ctrough) at Week 17 [ Time Frame: At Week 17 ]
7. - Incidence of adverse events (AEs) [ Time Frame: Up to 2 years 3 months ]
8. - Incidence of serious adverse events (SAEs) [ Time Frame: Up to 2 years 3 months ]
9. - Incidence of AEs leading to discontinuation [ Time Frame: Up to 2 years ]
10. - Incidence of deaths [ Time Frame: Up to 5 years ]
11. - Incidence of clinically significant changes in clinical laboratory results: Hematology tests [ Time Frame: Up to 2 years 3 months ]
12. - Incidence of clinically significant changes in clinical laboratory results: Chemistry panel tests [ Time Frame: Up to 2 years 3 months ]
13. - Efficacy parameters: disease control rate (DCR) by BICR with a minimum of 6 months follow-up [ Time Frame: Up to 2 years 6 months ]
14. - Efficacy parameters: DCR by BICR with a minimum of 12 months follow-up [ Time Frame: Up to 3 years ]
15. - Efficacy parameters: DCR by BICR at end of study [ Time Frame: Up to 5 years ]
16. - Efficacy parameters: duration of response (DOR) by BICR with a minimum of 6 months follow-up [ Time Frame: Up to 2 years 6 months ]
17. - Efficacy parameters: DOR by BICR with a minimum of 12 months follow-up [ Time Frame: Up to 3 years ]
18. - Efficacy parameters: DOR by BICR at end of study [ Time Frame: Up to 5 years
19. - Efficacy parameters: time to objective response (TTR) by BICR with a minimum of 6 months follow-up [ Time Frame: Up to 2 years 6 months ]
20. - Efficacy parameters: TTR by BICR with a minimum of 12 months followup [ Time Frame: Up to 3 years ]
21. - Efficacy parameters: TTR by BICR at end of study [ Time Frame: Up to 5 years ]
22. - Efficacy parameters: progression-free survival (PFS) by BICR with a minimum of 6 months follow-up [ Time Frame: Up to 2 years 6 months ]
23. - Efficacy parameters: PFS by BICR with a minimum of 12 months followup [ Time Frame: Up to 3 years ]
24. - Efficacy parameters: PFS by BICR at end of study [ Time Frame: Up to 5 years ]
25. - Efficacy parameters: overall survival (OS) with a minimum of 6 months follow-up [ Time Frame: Up to 2 years 6 months ]
26. - Efficacy parameters: OS with a minimum of 12 months follow-up [ Time Frame: Up to 3 years ]
27. - Efficacy parameters: OS at end of study [ Time Frame: Up to 5 years ]
28. - Efficacy parameters: ORR by BICR with a minimum of 12 months follow-up [ Time Frame: Up to 3 years ]
29. - Efficacy parameters: ORR by BICR at end of study [ Time Frame: Up to 5 years ]
30. - Incidence of anaphylactic, hypersensitivity, and systemic infusion reactions [ Time Frame: Up to 2 years 3 months ]
31. - Incidence of local injection- or infusion-site reactions [ Time Frame: Up to 2 years 3 months ]
32. - Percentage of participants who develop anti-nivolumab antibodies, if applicable [ Time Frame: Up to 2 years 3 months ]
33. - Percentage of participants who develop neutralizing antibodies, if applicable [ Time Frame: Up to 2 years 3 months ]

Investigational products

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

Test 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 Services Unlimited Company

Contact name

GSM-CT

Public contact point

Organisation

Bristol-Myers Squibb Services Unlimited Company

Contact name

GSM-CT

Third parties 25

Locations

9 EU/EEA countries · 26 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 84 files

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

Application history

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