BEBT-109 + pemetrexed + cisplatin

BEBT-109 + pemetrexed + cisplatin is a combination therapy under investigation for the treatment of non-small cell lung cancer (NSCLC) carrying epidermal growth factor receptor (EGFR) exon 20 insertion mutations. BEBT-109 is an orally administered, small molecule pan-mutant-selective inhibitor of EGFR, with potent activity against TKI-sensitive and TKI-resistant EGFR mutations, including T790M and exon 20 insertions, while sparing wild-type EGFR to reduce off-target toxicity. Pemetrexed is an antifolate chemotherapeutic agent that disrupts folate-dependent metabolic processes essential for cell replication. Cisplatin is a platinum-based chemotherapeutic that creates DNA crosslinks, leading to apoptosis in rapidly dividing cells. This combination is under evaluation as first-line or subsequent treatment for NSCLC with EGFR exon 20 insertion mutations and is designed to leverage the targeted activity of BEBT-109 with the established cytotoxic effects of platinum-based chemotherapy and antifolate chemotherapy[1][2][3][5][6].