M2698 + tamoxifen

M2698 + tamoxifen is a combination therapy that pairs M2698, a potent and selective dual inhibitor of p70S6K and AKT1/3 in the PAM pathway, with tamoxifen, a selective estrogen receptor modulator. This combination has been investigated in clinical trials for treating advanced breast cancer that has become resistant to multiple standard therapies. The combination aims to overcome treatment resistance by targeting both estrogen receptor signaling (via tamoxifen) and the PI3K/AKT/mTOR pathway (via M2698), which is a key regulator of tumor therapy resistance[1][6]. In a Phase 1 study, the combination demonstrated antitumor activity in patients with advanced breast cancer who had failed standard therapies. M2698 is notable for being an oral, brain-penetrant PAM pathway inhibitor that can mitigate the effects of the AKT feedback loop, a potential escape mechanism in resistant tumors[6]. The recommended Phase 2 dose for the M2698/tamoxifen combination was determined to be 160 mg QD/240 mg intermittent regimen[1].