NCT03937219.

Study name	COSMIC‐313
Methods	Study type: RCT, parallel assignment, phase III Blinding: yes, double‐ blind Accrual period: June 25, 2019 ‐ March 2025 (estimated study completion date) Countries: multicentre (167 study locations) Cross‐over study: no Status: Active, not recruiting (as of March 10, 2022)
Participants	Estimated enrolment: N = 840 Inclusion criteria: histologically confirmed advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) renal cell carcinoma with a clear‐cell component intermediate‐ or poor‐risk RCC as defined by International Metastatic RCC Database Consortium (IMDC) criteria measurable disease per RECIST 1.1 as determined by the Investigator Karnofsky Performance Status (KPS) ≥ 70%. adequate organ and marrow function all sexes, 18 years and older Exclusion criteria: prior systemic anticancer therapy for unresectable locally advanced or metastatic RCC including investigational agents uncontrolled, significant intercurrent or recent illness other clinically significant disorders such as: Autoimmune disease that has been symptomatic or required treatment within the past two years from the date of randomisation. Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomisation. Known history of COVID‐19 unless the participant has clinically recovered from the disease at least 30 days prior to randomisation major surgery (e.g., nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 4 weeks prior to randomisation any other active malignancy at time of randomisation or diagnosis of another malignancy within 3 years prior to randomisation 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 *Other protocol‐defined inclusion/exclusion criteria apply
Interventions	Experimental arm: cabozantinib + nivolumab + ipilimumab (4 doses) followed by cabozantinib + nivolumab Control arm: Cabozantinib‐matched placebo + nivolumab + ipilimumab (4 doses) followed by cabozantinib‐matched placebo + nivolumab
Outcomes	Primary outcome(s) PFS per RECIST 1.1 as determined by blinded independent radiology committee (time frame: up to 23 months after first participant randomised) Secondary outcome(s) OS (time frame: up to 69 months after first participant randomised) Relevant to this review but not reported: QoL, AEs/SAEs, TFST, number of patients who discontinued treatment Other outcomes (not relevant to this review): ‐
Starting date	June 25, 2019
Contact information	‐
Notes	Funding source: Exelixis