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Sitravatinib plus nivolumab demonstrates early efficacy in advanced NSCLC
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CHICAGO — The combination of sitravatinib and nivolumab conferred partial responses in a small cohort of patients who previously progressed on checkpoint inhibitor therapy, according to data from an ongoing phase 2 clinical trial presented at the International Association for the Study of Lung Cancer Multidisciplinary Symposium in Thoracic Oncology.
“Early signs of clinical activity have been observed in patients who have progressed following prior checkpoint inhibitor therapy,” Ticiana Leal, MD, assistant professor in the division of hematology/oncology and leader of the thoracic oncology program at University of Wisconsin School of Medicine and Public Health, told HemOnc Today. “Evidence of clinical activity has been seen in both patients with advanced NSCLC who had prior clinical benefit and no prior clinical benefit to PD-1/PD-L1 inhibitors.”
Sitravatinib (MGCD516, Mirati Therapeutics) — a spectrum-selective tyrosine kinase inhibitor — targets various receptor tyrosine kinases including Tyro3, Axl, and Mer and vascular endothelial growth factor family receptors.
“Inhibition of these target classes by sitravatinib may enhance antitumor activity through targeted depletion of immunosuppressive type 2 tumor-associated macrophages, regulatory T cells and myeloid-derived suppressor cells, increasing antigen presentation capacity of dendritic cells in the tumor microenvironment,” Leal said.
In the trial, patients with nonsquamous NSCLC who progressed on or after treatment with checkpoint inhibitor therapy, will receive oral sitravatinib in a continuous regimen with 240 mg nivolumab (Opdivo, Bristol-Myers Squibb) every 14 days on a 28-day cycle.
Researchers stratified patients by prior outcome with checkpoint inhibitor therapy, based on clinical benefit vs. progression of disease in 12 weeks or less.
Objective response rate by RECIST 1.1 serves as the primary endpoint. Secondary objectives include safety, tolerability, pharmacokinetics and changes in circulating and tumor cell PD-L1, circulating and tumor-infiltrating immune cell populations, cytokines and gene expression signatures.
As of Aug. 10, 2017, the study has enrolled 11 patients, six who demonstrated prior clinical benefit on checkpoint blockade and five who did not.
Early signs of clinical activity have been observed thus far, Leal said. This includes confirmed partial response in one patient among those with prior clinical benefit and in two patients with no prior benefit.
The first patient who achieved partial response is a 72-year-old female with pan wild-type metastatic NSCLC with history of treated brain metastases with multiple prior therapies. She previously received pembrolizumab (Keytruda, Merck) and had stable disease for 14 months, then obtained a confirmed partial response at the first disease evaluation.
The second patient is a 71-year-old female with pan wild-type metastatic NSCLC with multiple prior therapies who previously received nivolumab and previously experienced progressive disease as best overall response, but who obtained unconfirmed partial response at first disease evaluation.
The combination also showed an acceptable toxicity profile with manageable adverse events.
The study will continue to enroll patients, with efficacy data maturing.
Data will be updated and presented at the International Association for the Study of Lung Cancer 18th World Conference on Lung Cancer in October. – by Melinda Stevens
Reference:
Leal TA, et al. Abstract PS02.08. Presented at: International Association for the Study of Lung Cancer Multidisciplinary Symposium in Thoracic Oncology; Sept. 14-16, 2017; Chicago.
Disclosure: Leal reports no relevant financial disclosures.