Combination therapy with the novel TKI sitravatinib and the anti–PD-1 immune checkpoint inhibitor nivolumab (Opidvo) showed promising efficacy and safety in patients with clear cell renal cell carcinoma (RCC) and progression after antiangiogenic therapy, according to findings from a phase 1/2 trial published in the journal Science Translational Medicine.1,2
The investigational regimen yielded an objective response rate of 35.7% and a median progression-free survival of 11.7 months. The investigators also reported favorable tolerability, with the regimen eliciting no unexpected adverse events.
"This phase 1/2 trial established that the new drug sitravatinib can be safely and efficiently combined with the standard of care immunotherapy drug nivolumab to improve anti-cancer immune responses in patients with clear cell kidney cancer," study author Pavlos Msaouel, MD, PhD, an assistant professor at the University of Texas-MD Anderson Cancer Center in Houston, stated in a news release.
“If validated in the ongoing larger studies, the combination of sitravatinib with immunotherapy regimens can become a new arrow in our quiver for the treatment of cancer," added Msaouel.
Msaouel et al launched the trial after preclinical models showed the potential of sitravatinib to modulate immune-suppressive myeloid cells and thereby improve responses to anti–PD-1 treatments.
The study included 42 patients with ccRCC refractory to prior antiangiogenic therapies. Overall, 80.1% of these patients were alive at a median follow-up of 18.7 months. The investigators observed durable responses that were comparable among patients, regardless of whether or not they had liver metastases. They also noted that response to the immunotherapy/TKI regimen correlated with baseline peripheral blood neutrophil-to-lymphocyte ratio.
"Sitravatinib has independent anticancer efficacy against clear cell kidney cancer and may also enhance the efficacy of immune checkpoint therapies such as nivolumab," Msaouel stated in the news release.
"Additional phase 2 and phase 3 clinical trials are now investigating the combination of sitravatinib with nivolumab across different cancers, and ongoing clinical trials are now evaluating the safety and efficacy of adding sitravatinib to more potent immunotherapy regimens," Msaouel stated in his concluding remarks.
1. New Combo Immunotherapy Prolongs Survival in Patients With Advanced Kidney Cancer. Published online April 22, 2022. Accessed April 22, 2022. https://bit.ly/3k1DZ3g
2. Msaouel P, Goswami S, Thall PF, et al. A phase 1-2 trial of sitravatinib and nivolumab in clear cell renal cell carcinoma following progression on antiangiogenic therapy. Sci Transl Med. 2022;14(641):eabm6420. doi: 10.1126/scitranslmed.abm6420