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HARMONIC Evaluates Novel Combination in Growing Population of Never Smokers With Advanced Lung Cancer

*November 2022*

Never smokers represent a subgroup of patients with advanced lung cancer whose genetic makeup necessitates the need for targeted therapies and clinical trials aimed at improving outcomes. Compared with smokers, defined as those who smoke over 100 cigarettes in their life, never smokers have associated germline mutations for which targeted treatments may have demonstrative benefit.1,2

The investigational agent LP-300, which was unable to statistically demonstrate activity as a treatment for the general population of patients with advanced non–small cell lung cancer (NSCLC), may hold some potential to address the unmet need in never smokers. In combination with standard-of-care carboplatin and pemetrexed, LP-300 will be evaluated in never smokers with NSCLC in the phase 2 HARMONIC study (NCT05456256).2-4

“LP-300 was originally developed as a neuroprotective agent for chemotherapy,” Joshua Eric Reuss, MD, said in an interview with OncologyLive®. “It is a disodium salt that affects signaling pathways through modification of cysteine residues. In an original phase 3 trial [DMS32212R; NCT00966914], [LP-300] was studied with cisplatin and paclitaxel or cisplatin and paclitaxel alone in advanced NSCLC [non–small cell lung cancer]. There was a promising signal of efficacy in patients who were never smokers, which prompted its subsequent development and investigation in patients with driver mutations.”

Finding a Role for LP-300

In the prior DMS32212R study, the 2-year survival rate for patients receiving cisplatin and paclitaxel was 30% with the addition of LP-300 compared with 25% for those who received chemotherapy alone among all treated patients (n = 288). In the subgroup of never smokers (n = 87), the 2-year survival rate was 63% for those receiving LP-300 with chemotherapy compared with 28% for those receiving chemotherapy alone (HR, 0.519; P = .0462). Among women treated in the study (n = 114), a 65% increase in 2-year survival was observed with the addition of LP-300, with rates of 51% compared with 31% for the combination and control arms, respectively (HR, 0.579; P = .0477). Finally, in a subgroup analysis of women who were never smokers (n = 66), the 2-year survival rates were 72% vs 32%, with the combination and chemotherapy alone, respectively (HR, 0.367; P = .0167).3  

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