Investigational Drug
Sapanisertib
TrialFetch AI Analysis
Show TrialFetch AI Analysis
Overview
Sapanisertib (TAK-228, MLN0128, INK128 or CB-228) is an investigational oral cancer drug studied alone and with other treatments. Human trials have reported responses in some groups, but randomized phase 2 studies have not established a clear benefit over their comparison treatments. (pmc.ncbi.nlm.nih.gov)
Mechanism of action
Sapanisertib blocks the kinase mTOR in both of its signaling complexes, mTORC1 and mTORC2. These complexes help regulate cell growth, metabolism and survival. Unlike drugs that primarily inhibit mTORC1, sapanisertib inhibits the kinase through competition with ATP. (pmc.ncbi.nlm.nih.gov)
Efficacy
- Endometrial cancer: In a randomized phase 2 trial, the response rate was 24.4% with sapanisertib plus paclitaxel versus 18.4% with paclitaxel alone. Median progression-free survival was 5.6 versus 3.7 months, but the difference was not statistically significant; the trial did not meet its primary endpoint. The sapanisertib-alone arm had a 4.9% response rate and closed after a futility analysis. (pmc.ncbi.nlm.nih.gov)
- Renal cell carcinoma: In another randomized phase 2 trial, none of 26 response-evaluable patients receiving sapanisertib alone responded, versus 5 of 30 (16.7%) receiving everolimus. Progression-free survival was not significantly different. (pmc.ncbi.nlm.nih.gov)
- Other cancers: A small phase 2 lung-cancer cohort with NFE2L2-altered squamous tumors had a 25% response rate. In a randomized breast-cancer trial, adding sapanisertib to fulvestrant produced numerically longer progression-free survival, but the investigators did not support further development of those dosing schedules because of toxicity. These findings do not establish benefit across cancers. (pmc.ncbi.nlm.nih.gov)
Safety
Reported adverse effects include hyperglycemia, nausea, vomiting, mouth inflammation, diarrhea and rash. In the endometrial-cancer trial, grade 3 or worse adverse events occurred in 89.5% of patients receiving sapanisertib plus paclitaxel versus 54.0% receiving paclitaxel alone. In the breast-cancer trial, adverse events led to treatment discontinuation in 32%–36% of patients receiving sapanisertib plus fulvestrant, versus 4% receiving fulvestrant alone. (pmc.ncbi.nlm.nih.gov)
Further reading
- Randomized phase 2 endometrial-cancer trial
- Randomized phase 2 renal-cancer trial
- Randomized phase 2 breast-cancer trial
- Phase 1 mechanism and safety study
Last updated: Sep 2026
Active trials using Sapanisertib
Found 3 active trials using this drug:
TrialFetch AI summary: Women with previously treated HR-positive, HER2-negative advanced or metastatic breast cancer receive fulvestrant plus serabelisib, a PI3Kα inhibitor, and sapanisertib, an mTORC1/2 inhibitor, at one of two dose levels. The study evaluates safety and preliminary antitumor activity; patients previously treated with PI3K, AKT, or mTOR inhibitors are excluded.
ClinicalTrials.gov ID: NCT07558733
TrialFetch AI summary: Adults with advanced β-catenin-mutated HCC, Child-Pugh A liver function, and prior systemic therapy are treated with cabozantinib alone or combined with investigational sapanisertib, an mTORC1/2 inhibitor. The randomized portion requires one or two prior metastatic therapy lines and excludes prior cabozantinib.
ClinicalTrials.gov ID: NCT06811116
TrialFetch AI summary: Patients with unresectable advanced or recurrent endometrioid endometrial carcinoma, a PI3K/AKT/mTOR pathway alteration, and 1–4 prior systemic therapies, generally including platinum chemotherapy and a checkpoint inhibitor, receive paclitaxel plus sapanisertib (an mTORC1/2 inhibitor) and serabelisib (a PI3Kα inhibitor). A substudy adds an insulin-suppressing diet.
ClinicalTrials.gov ID: NCT06463028
