IMmotion151: A Randomized Phase III Study of Atezolizumab Plus Bevacizumab vs Sunitinib in Untreated Metastatic Renal Cell Carcinoma (mRCC)

BACKGROUND: Atezolizumab (atezo; anti–PD-L1) + bevacizumab (bev; anti-VEGF) showed first-line (1L) anti-tumor activity with a manageable safety profile in PD-L1+ mRCC pts in a Phase II study (McDermott ASCO-GU 2017). Here we describe the first randomized Phase III trial of a PD-L1/PD-1 pathway inhibitor combined with an anti-VEGF agent in 1L mRCC.

METHODS: IMmotion151 (NCT02420821) enrolled treatment-naïve pts regardless of prognostic risk group randomized 1:1 to receive atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w or sunitinib (sun) 50 mg PO QD 4 wk on/2 wk off. Pts were stratified by PD-L1 status (< 1% vs ≥ 1% PD-L1 expression on tumor-infiltrating immune cells [IC]; SP142 IHC assay). Coprimary endpoints: progression-free survival (PFS; by investigator per RECIST v1.1) in PD-L1+ pts (≥ 1% IC) and overall survival (OS) in intent-to-treat (ITT) pts. Secondary endpoints included PFS in ITT pts, ORR and DOR.

RESULTS: Baseline characteristics were comparable between arms within PD-L1+ (40% of ITT) and ITT pts. Median survival follow-up was 15 mo. PFS HR for atezo + bev vs sun was 0.74 (95% CI 0.57, 0.96) in PD-L1+ pts and 0.83 (95% CI 0.70, 0.97) in ITT pts. OS was immature at first interim analysis. PFS benefit was consistent across analyzed subgroups, including MSKCC risk, liver metastases and sarcomatoid histology. In PD-L1+ pts, ORR was 43% and DOR was not reached for atezo + bev vs 35% and 12.9 mo for sun. 40% of atezo + bev–treated pts and 54% of sun-treated pts had treatment-related Gr 3-4 AEs; 12% and 8% of treatment-related all-Gr AEs led to discontinuation, respectively.

CONCLUSIONS: The study showed longer PFS for atezo + bev vs sun in PD-L1+ pts. Improved PFS was also observed in ITT pts. Safety was consistent with that of the individual agents. These results support the use of atezo + bev as a 1L treatment option in mRCC. Clinical trial information: NCT02420821.


Robert J. Motzer, Thomas Powles, Michael B. Atkins, Bernard Escudier, David F. McDermott, Cristina Suarez, Sergio Bracarda, Walter Michael Stadler, Frede Donskov, Jae-Lyun Lee, Robert E. Hawkins, Alain Ravaud, Boris Y. Alekseev, Michael D. Staehler, Motohide Uemura, Francis Donaldson, Shi Li, Mahrukh A. Huseni, Christina Schiff, Brian I. Rini

Memorial Sloan Kettering Cancer Center, New York, NY; Barts Health NHS Trust – St Bartholomew’s Hospital, London, United Kingdom; Georgetown University Lombardi Comprehensive Cancer Center, Washington, DC; Gustave Roussy Institute, Villejuif, France; Beth Israel Deaconess Medical Center, Boston, MA; Vall d’Hebron Institute of Oncology, Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain; Ospedale San Donato, Arezzo, Italy; University of Chicago, Chicago, IL; Aarhus University Hospital, Aarhus, Denmark; University of Ulsan College of Medicine/ Asan Medical Center, Seoul, Korea, Republic of (South); Christie Hospital NHS Foundation Trust, Manchester, United Kingdom; Bordeaux University Hospital, Bordeaux, France; Federal State Institution, Moscow Research Oncological Institute, Moscow, Russia; University Hospital Munich-Grosshadern, Ludwig Maximilian University, Munich, Germany; Osaka University Graduate School of Medicine, Osaka, Japan; F. Hoffmann-La Roche Ltd., Basel, Switzerland; Genentech, Inc., South San Francisco, CA; Cleveland Clinic Taussig Cancer Institute, Cleveland, OH

Journal of Clinical Oncology 36, no. 6; DOI: 10.1200/JCO.2018.36.6_suppl.578