Lantern Pharma said the FDA raised no objections to proposed amendments for the Phase 2 HARMONIC™ trial evaluating LP-300 in never-smokers with advanced NSCLC, supporting a revised strategy focused on EGFR exon 21 L858R-mutant patients after TKI failure.
By: Regulatory Desk
Lantern Pharma announced that the U.S. Food and Drug Administration (FDA) raised no objections to proposed amendments for the ongoing Phase 2 HARMONIC™ trial evaluating LP-300 in never-smokers with advanced non-small cell lung cancer (NSCLC) adenocarcinoma. The feedback, which followed a recent Type C interaction, supports a revised development strategy focused on patients with EGFR exon 21 L858R mutations.
The HARMONIC™ trial is assessing LP-300 in combination with carboplatin and pemetrexed in never-smokers whose disease progressed after treatment with EGFR tyrosine kinase inhibitors (TKIs). Lantern emphasized that never-smoker NSCLC represents a distinct disease subtype with unique genomic features and accounts for an estimated 400,000 to 500,000 new cases globally each year.
Under the amended protocol, all future enrollment will focus exclusively on patients harboring EGFR exon 21 L858R mutations, which are associated with lower TKI binding affinity and poorer outcomes on osimertinib-based therapy compared with exon 19 deletions. Preliminary analyses from the ongoing study suggest this subgroup may derive greater benefit from the LP-300 triplet regimen, with multivariable Cox regression analyses identifying L858R mutation status as an independent predictor of progression-free survival benefit.
The FDA also supported Lantern’s proposal to extend LP-300 dosing from six to eight treatment cycles. The company noted that prior clinical experience involving more than 1,000 treated individuals showed the regimen remained generally well tolerated at the current dose level.
As part of the amendments, the HARMONIC™ trial will transition to a single-arm design and discontinue enrollment into the chemotherapy control arm, a move Lantern said reflects increasing challenges in randomizing patients in the rapidly evolving post-TKI treatment setting. The revised design is expected to accelerate enrollment and improve assessment of clinical activity within the targeted molecular subgroup.
Panna Sharma, President and Chief Executive Officer of Lantern Pharma, described the FDA interaction as an important milestone for the LP-300 program and said it supports the company’s strategy to focus on EGFR exon 21 L858R-mutant never-smoker NSCLC.
Emerging data from the trial showed a median progression-free survival of 8.3 months in EGFR exon 21 L858R-mutant patients treated with LP-300 plus chemotherapy after TKI failure, with no new safety signals observed.
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