Dr Reuss on the Investigation of LP-300 in Lung Adenocarcinoma

Joshua Reuss, MD, thoracic medical oncologist, MedStar Georgetown University Hospital, assistant professor, Department of Medicine, Georgetown University Medical Center, discusses the background of LP-300 and the rationale for evaluating the agent in the phase 2 HARMONIC trial (NCT05456256) in a never-smoker population of patients with advanced lung adenocarcinoma.

HARMONIC is a multicenter, open-label, phase 2 trial aiming to enroll approximately 90 patients in the United States. The study is evaluating LP-300 in combination with carboplatin and pemetrexed vs carboplatin and pemetrexed alone. The primary end points of the study are progression-free survival and overall survival, and secondary end points include objective response rate, duration of response, and clinical benefit rate.

LP-300 is a disodium salt that affects signaling pathways through modification of cysteine residues, and the agent was originally developed as a protective agent for chemotherapy, Reuss says. In a phase 3 trial (DMS32212R; NCT00966914), LP-300 was studied with cisplatin and paclitaxel vs carboplatin and paclitaxel alone in patients with advanced non–small cell lung cancer.

Findings from that study showed that in the overall population (n = 288), the 2-year survival rate for patients receiving LP-300 plus cisplatin and paclitaxel was 30%, compared with 25% for those who received chemotherapy alone. However, in the subgroup of never smokers (n = 87), the 2-year survival rate was 63% for those receiving LP-300 with chemotherapy vs 28% for those receiving chemotherapy alone (HR, 0.519; P = .0462).

The promising signal of efficacy in patients who were never smokers prompted the subsequent development and investigation of LP-300 in the HARMONIC trial, Reuss expands. Carboplatin plus pemetrexed is a standard chemotherapy regimen for patients with lung adenocarcinoma, and the mechanism of action of LP-300 could protect and amplify the effects of chemotherapy, Reuss says. By modulating oxidative stress and anti-angiogenesis, as well as reducing tumor resistance to chemotherapy, LP-300 could promote chemotherapy sensitivity, Reuss concludes.

Editor’s Note: In the prior phase 3 trial (NCT00966914), LP-300 was studied in combination with cisplatin and paclitaxel.