pimasertib + voxtalisib

Combination of the oral MEK1/2 inhibitor pimasertib (MSC1936369B) with the dual pan-PI3K and mTORC1/mTORC2 inhibitor voxtalisib (SAR245409, XL765), developed to achieve simultaneous blockade of the MAPK and PI3K/mTOR pathways in advanced solid tumors such as low-grade serous ovarian carcinoma and other solid malignancies. In a phase Ib dose-escalation/expansion study (NCT01390818), the MTD was pimasertib 90 mg QD plus voxtalisib 70 mg QD, and the RP2D was pimasertib 60 mg QD plus voxtalisib 70 mg QD; however, the combination showed poor long-term tolerability and limited antitumor activity overall. A randomized phase II study in recurrent LGSOC/LMP compared pimasertib 60 mg QD + voxtalisib 70 mg QD versus pimasertib 60 mg BID, finding low response rates and high discontinuation, leading to early termination. Preclinical studies showed synergistic antiproliferative effects across multiple tumor cell lines with combined MEK and PI3K/mTOR inhibition.[2][1][7][9][5]

Other names

pimasertib + SAR245409