FDA Grants Fast Track Designation to LP-184 for Glioblastoma

The FDA has granted fast track designation to LP-184 for the treatment of patients with glioblastoma (GBM).¹

LP-184, a small-molecule alkylating agent that causes tumor cell death via DNA damage, is currently under investigation in a phase 1a trial (NCT05933265) designed to assess its safety, tolerability, and maximum tolerated dose (MTD) in patients with various solid tumors, including GBM. Once the MTD has been determined, Lantern Pharma, the developer of LP-184, plans to advance the agent as STAR-001 in patients with GBM and other brain and central nervous system (CNS) cancers through its subsidiary, Starlight Therapeutics.

“Receiving FDA fast track designation for Lantern Pharma’s LP-184 in GBM reinforces our belief that this drug candidate can help in the critical need to find effective treatment options for patients with GBM and further supports the potential of LP-184 to address the challenges in aggressive CNS cancers, where patients have a critical need for novel and life-extending therapies,” Panna Sharma, president and chief executive officer of Lantern Pharma, stated in a news release.

The single-arm, multicenter, phase 1a trial is enrolling patients at least 18 years of age with histologically or cytologically documented advanced solid tumors that have relapsed after or are refractory to standard treatment, or for whom no standard treatment is available.2 Patients with GBM are required to have a Karnofsky performance status of greater than 60. Patients need to have measurable disease per RECIST 1.1 or Response Assessment in Neuro-Oncology criteria, as applicable; a life expectancy of longer than 3 months; and adequate liver, bone marrow, renal, and coagulation function at screening.

Key exclusion criteria include prior exposure to anticancer therapy within 2 weeks or at least 5 half-lives, whichever is shorter, or within 4 weeks of any immunotherapy, biologic, or any investigational therapy prior to the first dose of LP-184; a history of macular degeneration and/or retinopathy; prior exposure to radiation within 4 weeks of cycle 1 day 1; acute and severe viral, bacterial, or fungal infection; known or demonstrated viral infection of HIV or hepatitis B/C; clinically significant cardiac disease; clinically significant adverse effects (AEs) that have not returned to baseline or grade 1 or lower; major surgery within 4 weeks of the first dose of LP-184; and clinically active brain metastases. Notably, patients with treated brain metastases that are no longer symptomatic and do not require treatment with steroids may be included in the trial if they have recovered from the acute toxic effects of radiotherapy. At least 3 weeks must have elapsed between the end of whole-brain radiotherapy and trial enrollment.

The primary end point of the trial is the incidence and severity of AEs. Key secondary end points include the maximum plasma concentration (Cmax), the time to Cmax, the half-life, and the area under the plasma concentration vs time curve of the agent.

LP-184 was optimized using Lantern Pharma’s artificial intelligence platform RADR, which validates mechanisms that may be exploited in the clinical setting to target challenging-to-treat cancers.1 This agent has demonstrated synthetic lethality when used in combination with agents that induce DNA damage repair deficiency. Prior in vivo research has also shown that LP-184 causes double-strand breaks in the DNA of recurrent GBM cells.

In the future, Lantern Pharma plans to use RADR to assess the potential suitability of LP-184 in combination with other agents to control cancer progression in other patient subgroups.

References

1. Lantern Pharma’s investigational drug-candidate, LP-184, receives fast-track designation in glioblastoma from the FDA. News release. Lantern Pharma, Inc. October 15, 2024. Accessed October 15, 2024. https://ir.lanternpharma.com/news-events/press-releases/detail/163/lantern-pharmas-investigational-drug-candidate-lp-184
2. Study of LP-184 in patients with advanced solid tumors. ClinicalTrials.gov. Updated May 16, 2024. Accessed October 15, 2024. https://clinicaltrials.gov/study/NCT05933265