LJM716 + alpelisib

LJM716 + alpelisib is an investigational combination therapy pairing a HER3-targeted monoclonal antibody (LJM716) with the alpha-selective PI3K inhibitor alpelisib to overcome PI3K pathway–mediated resistance in HER2-positive, PIK3CA-mutated metastatic breast cancer. In a phase I trial with trastuzumab, continuous or intermittent alpelisib dosing with fixed-dose LJM716 and trastuzumab established MTDs but was limited by gastrointestinal toxicity; clinical activity included mostly stable disease with rare partial responses. Novartis sponsored early-phase studies of LJM716 combined with alpelisib, including an esophageal cancer program that was terminated early due to limited antitumor activity in Phase Ib. Alpelisib is an approved small-molecule PI3K-alpha inhibitor for other indications, marketed as Piqray and Vijoice, but LJM716 remains investigational. [Mechanism] Alpelisib selectively inhibits class I PI3K p110 alpha to block downstream signaling; LJM716 binds HER3 to prevent ligand-induced activation and feedback upregulation, aiming to enhance pathway suppression when combined with HER2 blockade. [Developers] Novartis developed both LJM716 and alpelisib.

Brand names

PiqrayVijoice

Other names

LJM716 plus alpelisibLJM-716 plus alpelisibLJM 716 plus alpelisibalpelisib + LJM716