Aim: We report clinical activity and safety of sitravatinib in patients with advanced cancer from basket cohorts with specific molecular alterations, in a Phase Ib study.Materials & methods: Patients with advanced solid tumors harboring amplification, mutation, or rearrangement of MET, AXL, RET, NTRK, DDR2, KDR, PDGFRA, KIT or CBL received sitravatinib once daily. Primary end point was confirmed objective response rate (ORR).Results: In total, 113 patients were enrolled following a median of 3 (range 1-18) prior systemic regimens. Altered RET (n = 31), CBL (n = 31) and MET (n = 17) were most frequent cohorts. Overall, 68.9% had reduced tumor volume and most (61.5%) had a best objective response of stable disease. ORR was highest in patients with RET-rearranged non-small cell lung cancer (21.1%) but did not differ significantly from the null hypothesis (ORR ≤15%; p = 0.316). Median progression-free survival and overall survival (5.7 and 24.2 months, respectively) were also longest in the RET-rearranged non-small cell lung cancer cohort. Diarrhea (61.1%), fatigue (50.4%) and hypertension (46.9%) were the most frequent treatment-emergent adverse events. Most treatment-emergent adverse events were mild-to-moderate in severity. The study closed before the planned number of patients were enrolled in all cohorts.Conclusion: Sitravatinib had a manageable safety profile with modest signals of clinical activity in patients with molecularly selected solid tumors.Clinical trial registration: www.clinicaltrials.gov identifier is NCT02219711.
Keywords: MGCD516; basket study; molecular alteration; sitravatinib; solid tumor.
We report findings from a clinical study of sitravatinib which included patients with cancer that could not be removed by surgery or had spread to other parts of the body. The tumors of these patients contained specific molecular changes in one of the following genes: MET, AXL, RET, NTRK, DDR2, KDR, PDGFRA, KIT or CBL. All patients received treatment with sitravatinib once a day. Change in tumor size over time was assessed to see how effective treatment with sitravatinib was.In total, 113 patients joined the study. Most patients had already received a median of three different types of medicines for their cancer (and up to 18 different types of anticancer medicines). Most patients had tumors that contained alterations in RET, CBL or MET genes.During the study, the percentage of patients who had a decrease in the tumor size was highest in the group with non-small cell lung cancer that contained an altered RET gene (21.1%). However, this level of response to sitravatinib was not considered high enough to be medically important.The most common side effects during the study were diarrhea (61.1%), fatigue (50.4%) and high blood pressure (46.9%). Most side effects were mild or moderate in severity. The study provided the opportunity to assess sitravatinib as a treatment for cancers with specific gene mutations that are uncommon; the study closed before the planned number of patients were enrolled.In conclusion, the side effects seen in patients who received sitravatinib were manageable. Signals of how well sitravatinib worked were modest in patients with cancer that had spread to other parts of the body and contained specific molecular changes.