LBA25 - Results from the phase II biomarker driven trial with nivolumab (N) and ipilimumab or VEGFR tyrosine kinase inhibitor (TKI) in naïve metastatic kidney cancer (m-ccRCC) patients (pts): The BIONIKK trial

Background

Nivolumab-ipilimumab (NI) and sunitinib/pazopanib (TKI) are indicated in m-ccRCC pts with IMDC intermediate/poor and good risk groups, respectively. Based on unsupervised analysis of genes expressed in m-ccRCC, we identified 4 groups (ccrcc1-4) with immune and angiogenic high/low features which could allow to better identify responders to either N, NI or TKI. We here report final analysis results of the BIONIKK trial.

Methods

BIONIKK is an open-label, French multicenter randomized phase 2 trial evaluating N vs. NI vs. TKI in upfront m-ccRCC according to ccrcc1-4 (35-gene signature, CITsig). ccrcc1,4 and ccrcc2,3 pts were randomized to receive N vs. NI and NI vs. TKI respectively. Primary endpoint (PE): objective response rate (ORR, RECIST1.1) per treatment and group. Secondary endpoints: progression-free survival (PFS), overall survival (OS) and tolerability. 150 pts were expected in target cohort (TC). An additional cohort was included to assess inter-platform variability.

Results

From 06/2017 to 07/2019: screened=308, randomized=202 (ALL), evaluable for PE=187 with TC=154. No correlation between ccrcc1-4 and IMDC risk groups (p=0.14). ORR (TC): N=30%, NI=44%, TKI=50%, with differences according to ccrcc1-4 (table1). ORR for NI were comparable across all groups. In ccrcc1 ORR for N was half that of NI while both were comparable in ccrcc4. In ccrcc2, ORR for TKI was as high as for NI. After a median (m) FU of 16 months (mo), mPFS (TC, mo): N=4.9, NI=10.4, TKI=NR, with again observed differences according to ccrcc1-4. OS data are not mature (events:16%). No new safety signal emerged compared to published data. CITsig in frozen and FFPE samples will be presented at the meeting. Table: LBA25

Conclusions

We demonstrate for the 1^st time in m-ccRCC pts that gene expression signatures may enable to enrich response rates. An extensive translational program is planned to identify new biomarkers.

Clinical trial identification

EudraCT: 2016-003099-28; NCT029609. Release date: November 10, 2016.

Editorial acknowledgement

Legal entity responsible for the study

Association pour la Recherche des Thérapeutiques Innovantes en Cancérologie.

Funding

Association pour la Recherche des Thérapeutiques Innovantes en Cancérologie - Bristol Myers Squibb.

Disclosure

Y. Vano: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Ipsen; Honoraria (institution), Advisory/Consultancy: Sanofi; Honoraria (institution), Advisory/Consultancy: Astellas; Travel/Accommodation/Expenses: Janssen. M. Bennamoun: Honoraria (institution), Advisory/Consultancy: Bristol Myers Squibb; Honoraria (institution), Advisory/Consultancy: Janssen; Honoraria (institution), Advisory/Consultancy: Sanofi; Honoraria (institution): Astellas. C.M. Chevreau: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol Myers Squibb; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Honoraria (self), Advisory/Consultancy: Novartis. D. Borchiellini: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol Myers Squibb; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy: Ipsen; Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: MSD. D. Pannier: Travel/Accommodation/Expenses: Bristol Myers Squibb; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Janssen. D. Maillet: Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol Myers Squibb; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen. M. Gross-Goupil: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol Myers Squibb; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen. C. Tournigand: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol Myers Squibb; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Research grant/Funding (self): Roche; Honoraria (self), Research grant/Funding (self): MSD; Honoraria (self), Travel/Accommodation/Expenses: Bayer; Honoraria (self), Research grant/Funding (self): Amgen. B. Laguerre: Honoraria (self): Bristol Myers Squibb; Honoraria (self): Ipsen; Honoraria (self): MSD; Honoraria (self): Roche; Travel/Accommodation/Expenses: Pfizer. P. Barthélémy: Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol Myers Squibb; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy, Travel/Accommodation/Expenses: Astellas; Advisory/Consultancy: Eusa Pharma. F. Joly: Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol Myers Squibb; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (institution), Advisory/Consultancy: Astellas; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (institution), Advisory/Consultancy: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy: Clovis. G. Gravis: Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol Myers Squibb; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (institution), Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (institution): Astellas; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (institution), Advisory/Consultancy: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen. S. Oudard: Honoraria (self): Bristol Myers Squibb; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): Merck; Honoraria (self): Sanofi; Honoraria (self): Astellas; Honoraria (self): Janssen. All other authors have declared no conflicts of interest.