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Spectrum-Selective Tyrosine Kinase Inhibitor Plus Nivolumab Under Study in NSCLC

By: Julia Fiederlein
Posted: Friday, October 29, 2021

In the phase II MRTX-500 trial, the tyrosine kinase inhibitor sitravatinib plus nivolumab demonstrated antitumor activity and “encouraging” overall survival, with no new safety signals, in patients with nonsquamous non–small cell lung cancer (NSCLC) who experienced disease progression during or after checkpoint inhibitor therapy. Ticiana A. Leal, MD, of the University of Wisconsin, Madison, and colleagues presented the updated efficacy data for those with prior clinical benefit during the European Society for Medical Oncology (ESMO) Congress 2021 (Abstract 1191O). This combination is being evaluated in the phase III SAPPHIRE study.

“Sitravatinib…reduces the number of myeloid-derived suppressor cells and regulatory T cells while increasing the ratio of M1/M2-polarized macrophages,” the investigators commented. “Thus, [sitravatinib] is hypothesized to overcome an immunosuppressive tumor microenvironment and augment antitumor immune responses.”

A total of 68 patients with prior clinical benefit from checkpoint inhibitor therapy were administered second- or third-line sitravatinib plus nivolumab. At a median follow-up of 28 months, the median duration of overall survival was 15 months; the rates of overall survival were 56% and 32% at 1 and 2 years, respectively. The median duration of progression-free survival was 6 months, and the objective response rate was 16%; this included two patients with a complete response. The median duration of response was 13 months.

Of the patients who underwent prior checkpoint inhibitor therapy and were evaluable for safety (n = 124), 91% experienced a treatment-related adverse event; grade 3 or 4 treatment-related adverse events were reported in 60% of this population. Hypertension and diarrhea were among the most frequently reported grade 3 or 4 treatment-related adverse events. No grade 5 treatment-related adverse events were observed. A total of 30% and 27% of patients discontinued treatment with sitravatinib and nivolumab, respectively.

Disclosure: For full disclosures of the study authors, visit oncologypro.esmo.org.



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