LP-300 Plus Chemo Yields Early Efficacy Results in Never-Smokers With NSCLC

Treatment with LP-300 in combination with pemetrexed (Alimta) and carboplatin led to disease control and may elicit durable responses in never-smokers with advanced non–small cell lung cancer (NSCLC) who have progressed following prior treatment with a TKI, according to preliminary findings from the phase 2 HARMONIC trial (NCT05456256).¹

Among the safety lead-in population (n = 7), LP-300 plus chemotherapy generated a clinical benefit rate (CBR)/disease control rate of 86%, and 6 patients continue to have clinical benefit to date. One patient had progressive disease. The combination also elicited a preliminary overall response rate (ORR) of 43%; 3 patients achieved a partial response (PR), and 3 patients had stable disease (SD). The 3 PRs included complete disappearance of metastatic lesions and/or normalization of lymph nodes that were considered abnormal at baseline. On average, the patients who achieved PR had a 51% reduction in tumor size per RECIST criteria. The patients with SD had an average 13% reduction in tumor size, and 2 patients each had a 40% reduction in distal tumor lesions.

One patient, who had been on the study for 14 months, experienced a 57% reduction in tumor size and a durable response. Median duration of response (DOR) and progression-free survival (PFS) data for the remaining 5 responders was not yet mature at the data cutoff date of July 25, 2024.

These preliminary efficacy findings were observed regardless of patients’ history of prior TKIs, metastatic disease sites, or demographics, including in patients with intermediate or low tumor mutational burden.

All 7 patients enrolled in the initial safety lead-in portion of the trial received LP-300 plus pemetrexed and carboplatin intravenously.

“These initial results from the HARMONIC trial provide preliminary clinical evidence of both the safety and the mode of action for LP-300 in never-smokers with NSCLC,” Reggie Ewesuedo, MD, MBA, the vice president of Clinical Development at Lantern Pharma, stated in a news release. “To see such a high CBR, which is part of our secondary end points, this early in the trial is a motivating factor for accelerating our enrollment globally.”

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

Investigators observed a safety profile with the combination that was consistent with that of the chemotherapy regimen alone. No dose-limiting toxicities were observed, and no patients discontinued treatment because of treatment-related toxicity. The most common AEs seen were decreased white blood cell counts and thrombocytopenia.

The randomization and expansion phase of the HARMONIC trial is currently ongoing and will evaluate primary end points of PFS and overall survival in approximately 80 additional patients who will be randomly assigned 2:1 to receive pemetrexed at 500 mg/m² plus carboplatin at an area under the concentration-time curve of 5 mg/mL per minute with or without LP-300 at 18.4 g/m² every 21 days for 4 to 6 cycles.² Secondary end points of the trial include ORR, DOR, CBR, and safety.

To be eligible for enrollment, patients need to be at least 18 years of age, have an ECOG performance status of 0 or 1, and have a confirmed histopathological diagnosis of inoperable advanced primary lung adenocarcinoma with specific actionable genomic alterations. A history of radiation therapy is allowed, provided that at least 1 area of tumor that is measurable per RECIST v1.1 criteria has not undergone prior irradiation and that any radiation therapy is completed and any radiation-induced sequelae are recovered at least 21 days before randomization. Select patients with documented stable central nervous system metastases are eligible for enrollment.

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 5, 2024. https://ir.lanternpharma.com/news-events/press-releases/detail/159/lantern-pharma-announces-positive-clinical-update-from
2. A study of LP-300 with carboplatin and pemetrexed in never smokers with advanced lung adenocarcinoma (HARMONIC). ClinicalTrials.gov. Updated July 8, 2024. Accessed August 5, 2024. https://clinicaltrials.gov/study/NCT05456256