Br J Cancer: Sapanisertib treats advanced solid tumors.

The PI3K/AKT/mTOR signal transductor is involved in regulating cell growth, proliferation and survival.
abnormal PI3K/AKT/mTOR signals are often observed in human cancer.
inhibition of mTOR reduces protein translation and prevents the proliferation of abnormal cells and tumor angiogenesty.
Sapanisertib is a highly selective mTOR kinase inhibitor that inhibits both mTORC1 and mTORC2.
phase 1 dose increment/expansion study focused on assessing the safety and tolerance of oral sapanisertib in patients with advanced solid tumors.
the subjects were given sapanisertib dose incremental dosages in four groups, as follows, once a day (QD, 31 patients); once a week (QW, 30 patients); three days at a time (QD x 3dQW, 33 patients); and five days at two days (QD x 5dQW, 22 patients).
in the extended cohort, a total of 82 patients with renal cell carcinoma (RCC), endometrial cancer, or bladder cancer received 5mg QD (39th), 40mg QW (26th) or 30mg QW (17th bit) sapanisertib.
results of Sapanisertib show that the maximum to-dosages of Sapanisertib are 6 mg QD, 40 mg QW, 9 mg QD x 3dQW and 7 mg QD x 5dQW.
Common dose-limiting toxicity (DLTs) include hyperglycemia, macular papules (QD), fatigue, and stomatitis (QD x 3dQW/QD x 5dQW);
one RCC patient received complete remission; nine patients received partial remission (seven for renal cell carcinoma; and one for bladder and endometrial cancers).
pharmacodynamics show that Sapanisertib is time-linear and supports repeated dosing.
pharmacodynamics showed a decrease in TORC1/2 biomarkers associated with treatment.
, in the Phase 1 study, the drug Sapanisertib showed controlled safety and initially observed anti-tumor activity in renal cell carcinoma and endometrial cancer.
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