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. 2023 May 4;2023(5):CD013798. doi: 10.1002/14651858.CD013798.pub2

NCT03141177.

Study characteristics
Methods Study name: CheckMate 9ER
Study design: RCT, phase III
Blinding: none, open‐label
Study Dates: September 2017 ‐ May 2019 (date of randomisation)
Date of data cut‐off: March 30, 2020 (for safety); exact dates for OS and PFS not reported, but we extracted data for the longest follow‐up time available (median 23.5 months)
Location: 18 countries, (Argentina, Australia, Brazil, Chile, Czech Republic, Germany, Greece, Israel, Italy, Japan, Mexico, Poland, Romania, Russia, Spain, Turkey, UK, USA), types of centres: not reported (only "local institutions")
Cross‐over study or cross over permitted: no
Participants Inclusion criteria:

  • all sexes

  • 18 years and older

  • histological confirmation of RCC with a clear‐cell component, including participants who may also have sarcomatoid features

  • advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) RCC

  • no prior systemic therapy for RCC with the following exception:

    • 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


Exclusion criteria:

  • any active CNS metastases

  • any active, known or suspected autoimmune disease

  • any condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomisation


Statement on CT.gov: "Other protocol defined inclusion/exclusion criteria could apply."
Sample size: N=651
Age, median (years, range): experimental arm: 62 (29‐90), control arm: 61 (28‐86)
Sex (m/f, (%)): experimental arm: 249/74 (77.1/22.9), control arm: 232/96 (70.7/29.3)
Prognostic factors:

  • IMDC risk score, n(%)

  • Favourable

  • experimental arm: 74 (22.9), control arm: 72 (22.0)

  • Intermediate

  • experimental arm: 188 (58.2), control arm: 188 (57.3)

  • Poor

  • experimental arm: 61 (18.9), control arm: 68 (20.7)

  • Previous nephrectomy, n(%)

  • Yes

  • experimental arm: 222 (68.7), control arm: 233 (71.0)

  • Karnofsky performance‐status score, n(%)

  • 90 or 100

  • experimental arm: 257 (79.6), control arm: 241 (73.5)

  • 70 or 80

  • experimental arm: 66 (20.4), control arm: 85 (25.9)

  • Not reported

  • experimental arm: 0 (0), control arm: 2 (0.6)
Interventions Experimental group (n = 323): nivolumab (240 mg, intravenous, every 2 weeks) + cabozantinib (40 mg, oral, once/day)
Control group (n =3 28): sunitinib (50 mg, oral, once/day) ‐ treatment was 4 weeks on treatment, 2 weeks off treatment (1 cycle = 6 weeks)
Outcomes Primary outcome(s)

  • PFS per BICR

    • Time frame: up to 29 months


Secondary outcome(s)

  • OS

    • Time frame: up to 40 months

  • Incidence of AEs

    • Time frame: up to 40 months

  • Incidence of SAEs

    • Time frame: up to 40 months

  • Incidence of AEs leading to discontinuation

    • Time frame: up to 40 months

  • Incidence of deaths

    • Time frame: up to 40 months

  • QoL (not stated on CT.gov).


Relevant to this review but not reported: TFST
Other outcomes (not relevant to this review): laboratory values, ORR
Notes Funding sources: Bristol‐Myers Squibb and others
Declarations of Interests:Quote: "Disclosure forms provided by the authors are available with the full text of this article at NEJM.org."
Clinical study report available: not yet
Study protocol available: yes
Statistical analysis plan available: yes

AEs: adverse events; ; v; CNS: central nervous system; CT: computed tomography; DCR: disease control rate; DR: duration of response; ECOG: Eastern Cooperative Oncology Group; ITT: intention‐to‐treat; KPS: Karnofsky Performance Status LDH: lactate dehydrogenase; MRI: magnetic resonance imaging; ORR: objective response rate; mTOR: mammalian target of rapamycin; OS: overall survival ; PFS: progression‐free survival ; QoL: quality of life; RCC: renal cell carcinoma; RR: response rate; SAEs: serious adverse events; SD: standard deviation; TTP: time to progression; VEGF: Vascular endothelial growth factor.

NCT not available for this study.