Synapse - Phase II trial of cabozantinib plus nivolumab in patients with non-clear-cell renal cell carcinoma and genomic correlates

Phase II trial of cabozantinib plus nivolumab in patients with non-clear-cell renal cell carcinoma and genomic correlates Journal Article

Authors:	Lee, C. H.; Voss, M. H.; Carlo, M. I.; Chen, Y. B.; Zucker, M.; Knezevic, A.; Lefkowitz, R. A.; Shapnik, N.; Dadoun, C.; Reznik, E.; Shah, N. J.; Owens, C. N.; McHugh, D. J.; Aggen, D. H.; Laccetti, A. L.; Kotecha, R.; Feldman, D. R.; Motzer, R. J.
Article Title:	Phase II trial of cabozantinib plus nivolumab in patients with non-clear-cell renal cell carcinoma and genomic correlates
Abstract:	Cabozantinib/nivolumab shows promising efficacy in non-clear-cell RCC w/ ORR of 48% in phase 2 study PURPOSE To assess the efficacy and safety of cabozantinib plus nivolumab in a phase II trial in patients with non-clear-cell renal cell carcinoma (RCC). PATIENTS AND METHODS Patients had advanced non-clear-cell renal carcinoma who underwent 0-1 prior systemic therapies excluding prior immune checkpoint inhibitors. Patients received cabozantinib 40 mg once daily plus nivolumab 240 mg once every 2 weeks or 480 mg once every 4 weeks. Cohort 1 enrolled patients with papillary, unclassified, or translocation-associated RCC; cohort 2 enrolled patients with chromophobe RCC. The primary end point was objective response rate (ORR) by RECIST 1.1; secondary end points included progression-free survival, overall survival, and safety. Next-generation sequencing results were correlated with response. RESULTS A total of 47 patients were treated with a median follow-up of 13.1 months. Objective response rate for cohort 1 (n = 40) was 47.5% (95% CI, 31.5 to 63.9), with median progression-free survival of 12.5 months (95% CI, 6.3 to 16.4) and median overall survival of 28 months (95% CI, 16.3 to not evaluable). In cohort 2 (n = 7), no responses were observed; one patient had stable disease > 1 year. Grade 3/4 treatment-related adverse events were observed in 32% treated patients. Cabozantinib and nivolumab were discontinued because of toxicity in 13% and 17% of patients, respectively. Common mutations included NF2 and FH in cohort 1 and TP53 and PTEN in cohort 2. Objective responses were seen in 10/12 patients with either NF2 or FH mutations. CONCLUSION Cabozantinib plus nivolumab showed promising efficacy in most non-clear-cell RCC variants tested in this trial, particularly those with prominent papillary features, whereas treatment effects were limited in chromophobe RCC. Genomic findings in non-clear-cell RCC variants warrant further study as predictors of response.
Keywords:	sunitinib; everolimus; open-label
Journal Title:	Journal of Clinical Oncology
Volume:	40
Issue:	21
ISSN:	0732-183X
Publisher:	American Society of Clinical Oncology
Date Published:	2022-07-20
Start Page:	2333
End Page:	2341
Language:	English
ACCESSION:	WOS:000827762800007
DOI:	10.1200/jco.21.01944
PROVIDER:	wos
PMCID:	PMC9287282
PUBMED:	35298296
Notes:	Article -- Source: Wos