SAR260301 + vemurafenib

SAR260301 + vemurafenib is a combination under investigation for the treatment of unresectable or metastatic BRAF-mutated melanoma, particularly in tumors with PTEN deficiency. **SAR260301** is an orally available, selective inhibitor of the phosphoinositide 3-kinase beta (PI3Kβ) isoform, designed to specifically target tumors with PTEN loss and thereby reduce PI3K pathway activity. **Vemurafenib** is a BRAF inhibitor approved for BRAF V600 mutation-positive melanoma, blocking the activity of mutant BRAF kinase within the MAPK pathway. Preclinical and clinical rationale supported that inhibiting both PI3Kβ (by SAR260301) and BRAF (by vemurafenib) could synergistically overcome therapy resistance and suppress tumor growth in PTEN-deficient/BRAF-mutant melanoma. The combination was explored for tolerability, optimal dosing, and preliminary efficacy but clinical development was terminated early due to unfavorable pharmacokinetics of SAR260301[1][3][4][5].