tivantinib + pemetrexed

**Tivantinib + pemetrexed** is an investigational combination therapy comprising tivantinib, a selective, oral, non-ATP-competitive small molecule inhibitor of the MET (hepatocyte growth factor receptor) and pemetrexed, a folate antimetabolite chemotherapeutic agent. The primary rationale behind this combination is to block MET-mediated signaling that promotes tumor growth, survival, and resistance, especially in cancers such as non-squamous non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma. Tivantinib inhibits the MET receptor and may also exert effects as a microtubule inhibitor, while pemetrexed inhibits folate-dependent enzymes involved in purine and pyrimidine synthesis, thereby preventing DNA and RNA synthesis in rapidly dividing cells. Clinical data indicate initial anti-tumor activity, but the combination (often also with carboplatin) remains in early-phase investigation for first-line therapy in advanced NSCLC and mesothelioma[1][2][5][3][4].