LP-300/Chemo Shows Clinical Benefit in Never Smokers With NSCLC

The safety profile of LP-300 plus chemotherapy in the phase 2 HARMONIC trial was comparable with prior reports of chemotherapy alone.

Combining the investigational small molecule candidate LP-300 with pemetrexed and carboplatin demonstrated positive preliminary results in a small cohort of patients with previously treated advanced non–small cell lung cancer (NSCLC) who were never smokers, according to data from the phase 2 HARMONIC trial (NCT05456256).¹

Study treatment yielded a clinical benefit rate (CBR) or disease control rate (DCR) of 86% (n = 6/7) among evaluable patients in the lead-in cohort. Additionally, the preliminary objective response rate (ORR) was 43%, which included partial responses (PRs) in 3 patients. Among those with a PR, tumor size reductions occurred at an average of 51% per RECIST criteria. Additionally, the average tumor size reduction among 3 patients with stable disease was 13%, with 2 patients experiencing distal lesion reductions of 40% in size.

Investigators reported that 1 patient has been on study treatment for 14 months; this patient has experienced a 57% tumor size reduction and a significant duration of response (DOR). As of the data cutoff of July 25, 2024, data have not yet matured for estimating the median DOR and progression-free survival (PFS). Treatment with LP-300 plus chemotherapy appeared to be effective among patients regardless of prior tyrosine kinase inhibitor (TKI) therapy, demographics, and metastatic disease sites.

The study regimen had a predictable safety profile that was comparable with prior reports of chemotherapy alone in this population. Investigators observed no dose-limiting toxicities, and no patients discontinued therapy due to treatment-related toxicity. Frequent adverse effects (AEs) included decreased white blood counts and thrombocytopenia.

“Preliminary results indicate that this LP-300 triplet regimen is active against advanced NSCLC with actionable alterations and there were no unexpected [AEs],” Janakiraman Subramanian, MD, director of Thoracic Oncology at Inova Schar Cancer Institute, stated in the press release.1 “Also, the early Harmonic patient data indicates that the [AEs] appear to be primarily due to chemotherapy and not the study drug.”

Developers designed LP-300 to exhibit a multimodal mechanism of action targeting tyrosine kinase receptors and cell redox enzymes. Investigators hypothesize that the agent may regulate cellular redox in critical signaling pathways in patients with NSCLC, thereby directly interacting with TKI receptors through cysteine modification.

Investigators of the multicenter, open-label HARMONIC trial plan to enroll up to 90 patients with NSCLC who have never smoked following disease progression on a prior TKI. After completing the safety lead-in portion of the trial, investigators will randomize patients 2:1 to receive LP-300 plus carboplatin/pemetrexed or chemotherapy alone.

The trial’s primary end points include PFS and overall survival.² Secondary end points include ORR, DOR, CBR, and safety.

Patients 18 years and older with a confirmed histopathological diagnosis of inoperable advanced primary adenocarcinoma of the lung who have never smoked or smoked fewer than 100 cigarettes or equivalent products are eligible for enrollment on the trial. Other eligibility criteria include having an ECOG performance status of 0 or 1, stable central nervous system (CNS) metastases, and adequate bone marrow and hepatic function.

In April 2024, developers received regulatory approval to expand the HARMONIC trial to Japan and Taiwan.³

“These initial results from the Harmonic trial provide preliminary clinical evidence of both the safety and the mode of action for LP-300 in [patients who have never smoked] with NSCLC. To see such a high [CBR], which is part of our secondary endpoints, this early in the trial is a motivating factor for accelerating our enrollment globally,” concluded Reggie Ewesuedo, MD, MBA, vice president of Clinical Development at Lantern, the developer of LP-300.¹

References

1. Lantern Pharma announces positive clinical update from ongoing phase 2 HARMONIC™ clinical trial for never smokers with advanced NSCLC, including an 86% clinical benefit rate in the initial patient cohort. News release. Lantern Pharma. August 5, 2024. Accessed August 6, 2024. https://tinyurl.com/4a67zm43
2. A study of LP-300 with carboplatin and pemetrexed in never smokers with advanced lung adenocarcinoma (HARMONIC). ClinicalTrials.gov. Accessed August 6, 2024. https://tinyurl.com/5daber34
3. Lantern Pharma receives regulatory approval to expand Harmonic™ clinical trial for non-small cell lung cancer in never-smokers into Japan and Taiwan. News release. Lantern Pharma. April 22, 2024. Accessed August 6, 2024. https://tinyurl.com/r6dw42yy