NCT04203901.

Study name	‐
Methods	Study type: RCT, phase IIb Blinding: no, open‐label Accrual period: July 22, 2020 ‐ March, 2022 (estimated study completion date) Countries: national (USA), single‐ centre (Texas) Cross‐over study: no Status: Recruiting (as of Februrary 11, 2022)
Participants	Estimated enrolment: N=120 Inclusion criteria: age ≥ 18 years, all sexes advanced disease histologically assessed as RCC, with predominantly clear cell histology metastatic disease (measurable or non‐measurable) that can be monitored throughout the course of study participation per iRECIST participants who are candidates for standard first‐line therapy time from initial RCC diagnosis to initiation of systemic treatment (Nivolumab+Ipilimumab) of <1 year Karnofsky Performance Status (KPS) ≥ 70% resolution of all acute toxic effects of prior radiotherapy or surgical procedures to Grade ≤ 1 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Exclusion criteria: prior systemic therapy (including adjuvant or neoadjuvant) of any kind for RCC, including immunotherapy, chemotherapy, hormonal, or investigational therapy prior history of malignancy within the preceding 3 years, except for adequately treated in situ carcinomas or non‐melanoma skin cancer, adequately treated early stage breast cancer, superficial bladder cancer, and non‐metastatic prostate cancer with a normal PSA history of or known brain metastases, spinal cord compression, or carcinomatous meningitis, or evidence of brain or leptomeningeal disease participants will be excluded if they have <2 of the following risk factors at Screening: Time from diagnosis to systemic treatment < 1 year Hgb < LLN Corrected calcium > 10.0 mg/dLKPS < 80% Neutrophils > ULNPlatelets > ULN NCI CTCAE Grade 3 haemorrhage < 28 days before Visit 1 (Week 0) any serious medical condition or illness considered by the investigator to constitute an unwarranted high risk for investigational treatment *Other protocol‐defined inclusion/exclusion criteria apply
Interventions	Experimental arm: CMN‐001 and Nivolumab+Ipilimumab (1st line therapy), Lenvatinib + Everolimus (2nd line therapy after progression) Control arm: Nivolumab+Ipilimumab (1st line therapy), Lenvatinib + Everolimus (2nd line therapy after progression)
Outcomes	Primary outcome(s) OS (time frame: through study completion, an average of 2 years), participants will be followed for OS until the completion of the study Secondary Outcome(s) treatment emergent adverse events (TEAEs) between both arms (time frame: through study completion, an average of 2 years) PFS (time frame: through study completion, an average of 2 years, assessed by the investigator per iRECIST) Relevant to this review but not reported: QoL, SAEs, TFST, number of patients who discontinued treatment Other outcomes (not relevant to this review): tumour response
Starting date	July 22, 2020
Contact information	CoImmune; Mark DeBenedette, PhD
Notes	Funding source: CoImmune