This is a randomized, double-blind, controlled trial to evaluate the efficacy and safety of cabozantinib in combination with nivolumab and ipilimumab versus nivolumab and ipilimumab in previously untreated subjects with intermediate- and poor-risk advanced or metastatic RCC

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Exelixis Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

3 Oct 2019 → ongoing

Decision date (initial)

2024-10-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-515616-47-00

EudraCT number

2018-004567-31

WHO UTN

U1111-1312-1560

ClinicalTrials.gov

NCT03937219

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

The objective of this study is to evaluate the efficacy and safety of cabozantinib in combination with nivolumab and ipilimumab versus nivolumab and ipilimumab in previously untreated subjects with intermediate- and poor-risk advanced or metastatic RCC.

Conditions and MedDRA coding

Metastatic Renal Cell Carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1. Histologically confirmed advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) renal cell carcinoma with a clear-cell component.
2. 2. Intermediate- or poor-risk RCC as defined by International Metastatic RCC Database Consortium (IMDC) criteria.
3. 3. Measurable disease per RECIST 1.1 as determined by the Investigator.
4. 4. Karnofsky Performance Status (KPS) ≥ 70%.
5. 5. Adequate organ and marrow function.

Exclusion criteria 5

1. 1. Prior systemic anticancer therapy for unresectable locally advanced or metastatic RCC including investigational agents.
2. 2. Uncontrolled, significant intercurrent or recent illness including, but not limited to serious cardiovascular disorders (including uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment), GI disorders associated with high risk for perforation or fistula formation, tumors invading GI tract, bowel obstruction, intra-abdominal abscess, clinically significant bleeding events, cavitating pulmonary lesions, or lesion invading major pulmonary blood vessels.
3. 3. Other clinically significant disorders such as: i. Autoimmune disease that has been symptomatic or required treatment within the past two years from the date of randomization. ii. Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. iii. Active infection requiring systemic treatment. Acute or chronic hepatitis B or C infection, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or known positive test for tuberculosis infection where there is clinical or radiographic evidence of active mycobacterial infection. iv. Known history of COVID-19 unless the subject has clinically recovered from the disease at least 30 days prior to randomization.
4. 4. Major surgery (eg, nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 4 weeks prior to randomization. Minor surgeries within 10 days prior to randomization. Subjects must have complete wound healing from major or minor surgery before randomization.
5. 5. Any other active malignancy at time of randomization or diagnosis of another malignancy within 3 years prior to randomization that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Duration of PFS (Progression-Free Survival), per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), by Blinded Independent Radiology Committee (BIRC)

Secondary endpoints 1

1. Duration of OS (overall survival)

Investigational products

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

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Exelixis Inc.

Sponsor organisation

Exelixis Inc.

Address

1851 Harbor Bay Parkway

City

Alameda

Postcode

94502-3010

Country

United States

Scientific contact point

Organisation

Exelixis Inc.

Contact name

Exelixis Medical Affairs

Public contact point

Organisation

Exelixis Inc.

Contact name

Exelixis Medical Affairs

Third parties 5

Locations

9 EU/EEA countries · 47 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 58 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