ESMO Virtual Congress 2020: Results from the Phase 2 Biomarker Driven Trial with Nivolumab and Ipilimumab or VEGFR Tyrosine Kinase Inhibitor in Naïve Metastatic Kidney Cancer Patients: The BIONIKK Trial

(UroToday.com) Sunitinib has been the standard first-line treatment for metastatic clear cell RCC since 2007. However, nivolumab plus ipilimumab combination therapy has been recently approved in upfront treatment of metastatic clear cell RCC patients with IMDC intermediate/poor risk groups based on data in the CheckMate-214 trial.1 In this trial, the objective response rate (ORR) was 42% for nivolumab plus ipilimumab versus 27% for sunitinib; the median PFS was 11.6 months for nivolumab plus ipilimumab, compared to 8.4 months for sunitinib. In unselected metastatic clear cell RCC patients, frontline nivolumab provided a 28.7% objective response rate and a median PFS of 5.54 months.2 Analysis of transcriptomic data from frozen clear cell RCC tumors revealed four groups of patients (ccrcc1-4) with immune and angiogenic high/low features which could allow to better identify responders to either nivolumab, nivolumab plus ipilimumab or TKI. ccrcc1 “immune-low” and ccrcc4 “immune-high” tumors have been associated with the poorest outcomes, whereas ccrcc2 “angio-high” and ccrcc3 “normal-like” tumors have been associated with the best outcomes. The hypothesis for this study was that nivolumab should provide good outcomes for ccrcc4, nivolumab plus ipilimumab should be necessary to improve outcomes in ccrcc1, and TKIs (sunitinib or pazopanib) should provide good outcomes for ccrcc2 and ccrcc3. At the kidney cancer session at the virtual ESMO 2020 annual meeting, Dr. Yann Vano and colleagues provided the final results of the BIONIKK trial.


BIONIKK is an open-label, French multicenter randomized phase 2 trial evaluating nivolumab versus nivolumab plus ipilimumab versus TKI in upfront metastatic clear cell RCC according to ccrcc1-4 (35-gene signature). ccrcc1 and ccrcc4 patients were randomized to nivolumab versus nivolumab plus ipilimumab, whereas ccrcc2 and ccrcc3 patients were randomized to receive nivolumab plus ipilimumab versus TKI. The primary endpoint for this study was objective response rate (ORR, RECIST1.1) per treatment and group. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and tolerability. A total of 150 patients were expected in the target cohort and an additional cohort was included to assess inter-platform variability. A summary of the trial design is as follows:

ESMO_BIONIKK.png

Between June 2017 and July 2019, 308 patients were screened and 202 patients were randomized, with target cohort of 187 patients, and an evaluable cohort of 154 patients. Baseline demographics were comparable between the ccrcc1-4 groups:

ESMO_BIONIKK_trial.png

For ccrcc1, nivolumab plus ipilimumab resulted in an ORR of 39.4%, whereas for ccrcc4 the combination resulted in an ORR of 53.0%. In ccrcc2, nivolumab plus ipilimumab resulted in an ORR of 48.3 months, whereas for ccrcc3 the combination resulted in an ORR of 25.0%:

ESMO_VEGFR_tyrosine.png



After a median follow-up of 16 months the mPFS results are as follows:
  • ccrcc1: nivolumab plus ipilimumab 8.0 months vs nivolumab 4.6 months
  • ccrcc4: nivolumab plus ipilimumab 12.2 months vs nivolumab 7.8 months
  • ccrcc2: TKI not reached vs nivolumab plus ipilimumab 10.4 months

OS data are not yet mature, as there have only been 16% of the necessary events. The median time to response and duration of response are summarized as follows:

ESMO_Dr._Vano.png

No new safety signal emerged compared to published data: the grade 3-4 adverse event rates ranged from 18%-55% among the trial arms.  

Dr. Vano concluded this presentation of the BIONIKK trial with the following take-home messages:
  • This is the first randomized clinical trial based on prospective and real-time molecular group assessment to guide therapy in front-line metastatic clear-cell RCC
  • There as a high response rate for nivolumab alone for patients with ccrcc4 tumors with durable responses
  • For patients with ccrcc1 tumors, combination with nivolumab plus ipilimumab is needed
  • For patients with ccrcc2 tumors, TKIs provide very high response rates and non-reached mPFS after 16 months of follow-up

Presented by: Yann Vano, MD, Medical Oncology, Hôpital Européen Georges Pompidou, AP-HP Centre – Université de Paris, Paris, France; Centre de Recherche des Cordeliers, INSERM, Universitéde Paris, Sorbonne Université, Paris, France, Paris, France

Co-Authors: R.T. Elaidi,2 M. Bennamoun,3 C.M. Chevreau,4 D. Borchiellini,5 D. Pannier,6 D. Maillet,7 M. Gross-Goupil,8 C. Tournigand,9 B. Laguerre,10 P. Barthélémy,11 F. Joly,12 G. Gravis,13 S. Caruso,14 C-M. Sun,15 V. Verkarre,16 W-H. Fridman,15 J. Zucman-Rossi,14 C. Sautès-Fridman,15 S. Oudard17

Affiliations: 2 Medical Oncology, ARTIC - Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie; Hôpital Européen Georges Pompidou, AP-HP Centre – Université de Paris, Paris, France, Paris, France, 3 Medical Oncology, Institut Mutualiste Montsouris, Paris, France, 4 Medical Oncology, Institut Universitaire du Cancer -Toulouse- Oncopole, Toulouse, France, 5 Medical Oncology, Centre Anticancer Antoine Lacassagne, Nice, France, 6 Medical Oncology, Centre Oscar Lambret, Lille, France, 7 Medical Oncology, Centre Hospitalier Lyon Sud, Pierre Bénite, France, 8 Medical Oncology, Centre Hospitalier Universitaire de Bordeau - Hôpital Saint-André, Bordeaux, France, 9 Medical Oncology, Centre Hospitalier Universitaire Henri-Mondor, Créteil, France, 10 Medical Oncology, Centre Eugene - Marquis, Rennes, France, 11 Medical Oncology, Hôpitaux Universitaires de Strasbourg/ Institut de Cancérologie Strasbourg Europe, Strasbourg, France, 12 Medical Oncology, Centre François Baclesse, Caen, France, 13 Medical Oncology, Institut Paoli Calmettes, Institut Paoli-Calmettes, Aix-Marseille Université, Marseille, France, 14 Functional Genomics of Solid Tumors, Centre de Recherche des Cordeliers, INSERM, Universitéde Paris, Sorbonne Université, Paris, France, Paris, France, 15 Inflammation, Complement and Cancer, Centre de Recherche des Cordeliers, INSERM, Universitéde Paris, Sorbonne Université, Paris, France, 16 Pathology, Hôpital Européen Georges Pompidou, AP-HP Centre – Université de Paris, Paris, France 17 Medical Oncology, Hôpital Européen Georges Pompidou, AP-HP Centre – Université de Paris; Immunotherapy and Anti-Angiogenic Therapy in Oncology, Université de Paris, INSERM, PARCC, Paris, France

Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 2020 European Society for Medical Oncology Virtual Congress (#ESMO20), September 19th-September 21st, 2020.

References:

  1. Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carinoma. N Engl J Med 2018;378(14):1277-1290.
  2. Grimm MO, Schmidinger M, Martinez ID, Tailored immunotherapy approach with nivolumab in advanced renal cell carcinoma (TITAN-RCC). Ann Oncol 2019;30(5):V892.
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