Vivek Subbiah, MD Targeting the mTOR pathway with dual inhibitors of mTORC1 and mTORC2 such as sapanisertib (CB-228) can be effective for the treatment of patients with solid tumors when the mTOR inhibitor is used as a component of a combination regimen, according to Vivek Subbiah, MD. When sapanisertib was combined with the antidiabetic agent metformin in a phase 1 study (NCT03017833), 79% of response-evaluable patients with locally advanced or metastatic solid tumors (n = 19/24) achieved disease control. Additionally, 17% of patients achieved a partial response (PR) and of 3 of the 4 patients with a PR had PTEN mutations; 2 of the 4 patients with a response also had comutations.
1 Findings from another phase 1 study (NCT02159989) showed that response-evaluable patients who received sapanisertib plus ziv-aflibercept (n = 50) experienced a disease-control rate (DCR) of 78%; 74% of patients experienced stable disease (SD) and 2 patients achieved a PR.2 “Drug development in the mTORC1/2 space has been challenging,” Subbiah said. “[Sapanisertib] and multiple other drugs have been tested in patients in a non-biomarker driven fashion.
These 2 combination studies have clearly shown that mTORC1/2 inhibitors such as sapanisertib in combination [regimens] have activity in patients who harbor specific alterations. The next step should be to use these mTORC1/2 inhibitors in combination [with other agents] in specific biomarker driven and targeted populations.” In an interview wit.