A Phase 3 Study of Nivolumab plus Ipilimumab Versus Sunitinib in untreated Subjects with Advanced or Metastatic Renal Cell Carcinoma (RCC)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bristol Myers Squibb International Corporation

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 Nov 2014 → 21 Mar 2025

Decision date (initial)

2023-09-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Bristol-Myers Squibb International Corporation, Belgium

External identifiers

EU CT number

2023-504761-23-00

EudraCT number

2014-001750-42

WHO UTN

U1111-1161-0444

ClinicalTrials.gov

NCT02231749

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

The purpose of this study is to compare the progression free survival and the overall survival of nivolumab combined with ipilimumab to sunitinib monotherapy in patients with previously untreated Renal Cell Cancer

Secondary objectives 8

1. Progression-free survival
2. Overall survival
3. Objective response rate
4. Duration of objective response
5. Overall safety and tolerability
6. Disease related symptom progression
7. Health related quality of life
8. Healthcare resource utilization

Conditions and MedDRA coding

Advanced or metastatic renal cell carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Histological confirmation of RCC with a clear-cell component
2. Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) RCC
3. No prior systemic therapy for RCC with the following exception: a) One prior adjuvant or neoadjuvant therapy for completely resectable RCC if such therapy did not include an agent that targets VEGF or VEGF receptors and if recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy.
4. Karnofsky Performance Status (KPS) of at least 70%
5. Measurable disease as per RECIST 1.1
6. Tumor tissue (formalin-fixed paraffin-embedded (FFPE) archival or recent acquisition) must be received in order to randomize a subject to study treatment. (Note: Fine Needle Aspiration [FNA] and bone met by the central vendor (block or unstained slides) astases samples are not acceptable for submission)

Exclusion criteria 5

1. Any history of or current CNS metastases. Baseline imaging of the brain is required within 28 days prior to randomization
2. Prior systemic treatment with VEGF or VEGF receptor targeted therapy (including, but not limited to, sunitinib, pazopanib, axitinib, tivozanib, and bevacizumab)
3. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
4. Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (> 10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll
5. Any condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medication within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoints are overall survival and progression free survival

Secondary endpoints 9

1. Overall survival
2. Objective response rate
3. Duration of objective response
4. Overall safety and tolerability
5. Disease related symptom progression
6. Health related quality of life
7. Healthcare resource utilization
8. Adverse Event Incidence Rate
9. Progression-free survival

Investigational products

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

Test 2

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bristol Myers Squibb International Corporation

Sponsor organisation

Bristol Myers Squibb International Corporation

Address

Terhulpsesteenweg 185

City

Watermaal-Bosvoorde

Postcode

1170

Country

Belgium

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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 44 files

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

Application history

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