LP-184 Earns 3 FDA Rare Pediatric Disease Designations Across Ultra-Rare Tumor Types

Panna Sharma

The next-generation alkylating agent LP-184 has received 3 rare pediatric disease designations (RPDD) from the FDA as potential treatment options for patients with malignant rhabdoid tumors (MRT), rhabdomyosarcoma (RMS), and hepatoblastoma, according to an announcement from Lantern Pharma.¹

These regulatory decisions were supported by data from specialized models showing signs of tumor regression and prolonged event-free survival. Such models were developed as part of the Pediatric Preclinical Testing Program, which aims to identify novel therapies that could have significant activity against childhood cancers and is supported by the National Cancer Institute.

LP-184 was previously granted RPDD for atypical teratoid rhabdoid tumors (ATRT). Additionally, the agent received FDA orphan drug designation as a potential therapeutic option for patients with glioblastoma multiforme and other malignant gliomas in August 2021.²

“At Lantern, we’re harnessing artificial intelligence [AI] and data-driven approaches to revolutionize cancer drug development, aiming to dramatically reduce costs, accelerate timelines, and enhance precision in bringing new therapies to patients,” Panna Sharma, chief executive officer and president of Lantern Pharma, stated in a news release.¹ “Our recent breakthrough in identifying 3 additional, high-potential indications for LP-184 in pediatric cancers exemplifies this progress. We believe that ‘AI for good’ should address both blockbuster opportunities as well as rare, often overlooked pediatric cases. The FDA’s RPDD for these 3 potential programs is a testament to this commitment. We’re acutely aware that patients and their families are relying on innovators like us to speed up therapy development. These designations mark a crucial step forward in advancing our expanding portfolio of pediatric programs targeting these devastating and rare cancers. It reinforces our dedication to transforming hope into tangible solutions for those who need them most.”

The small molecule drug candidate LP-184 leverages synthetic lethality to preferentially damage DNA in tumor cells that overexpress select biomarkers or display DNA damage repair deficiencies. Preclinical studies have shown antitumor activity with the agent across in vitro and in vivo models of solid tumors, including pancreatic cancer, bladder cancer, triple-negative breast cancer, glioblastoma, brain metastases, and ATRT. Moreover, the agent may show enhanced efficacy when used alongside FDA-approved therapies and modalities such as spironolactone, PARP inhibitors, and radiation therapy.³

LP-184 is currently being evaluated in a phase 1 trial (NCT05933265) of patients with advanced or metastatic solid tumors who have experienced relapse after, or are refractory to, standard therapies or for whom no standard therapies are available.1 Results from this and other clinical trials may support the future development of trials evaluating select pediatric subgroups with ATRT, MRT, RMS, and hepatoblastoma.

Phase 1 Trial Design

This single-arm, multicenter, dose-escalation study is enrolling patients at least 18 years of age with histologically or cytologically confirmed advanced solid tumors whose disease is relapsed/refractory to standard therapies or has no standard therapies available. Acute effects of any prior therapy must be resolved to baseline severity or no higher than grade 1, except adverse effects not considered a safety risk, per investigator judgment. Patients must also have an ECOG performance status of 0 or 1, or a Karnofsky performance status of more than 60 for patients with glioblastoma; measurable disease per RECIST 1.1 or RANO criteria; and a life expectancy of at least 3 months.⁴

The trial aims to enroll approximately 50 to 60 patients.¹ Upon enrollment, patients will receive an intravenous infusion of LP-184 on days 1 and 8 per 21-day cycle for at least 2 cycles. Dosing will be determined based on the available cohort at the time of each patient’s enrollment.³

The primary objective of the study is to assess the safety and tolerability of escalating doses of LP-184 to identify the maximum tolerated dose and recommended phase 2 dose.¹

References

1. Lantern Pharma announces three U.S. FDA rare pediatric disease designations granted to LP-184 in multiple ultra rare children’s cancers. News Release. Lantern Pharma, Inc. September 23, 2024. Accessed September 23, 2024. https://ir.lanternpharma.com/news-events/press-releases/detail/162/lantern-pharma-announces-three-u-s-fda-rare-pediatric
2. FDA grants Lantern Pharma additional orphan drug designation for drug candidate LP-184 in glioblastoma multiforme & malignant gliomas. News release. Lantern Pharma. August 30, 2021. Accessed September 23, 2024. https://ir.lanternpharma.com/news-events/press-releases/detail/59/fda-grants-lantern-pharma-additional-orphan-drug
3. Lantern Pharma announces first patient dosed in the phase 1 study for LP-184 in advanced solid tumors. News release. Lantern Pharma. September 25, 2023. Accessed September 23, 2024. https://ir.lanternpharma.com/news-events/press-releases/detail/138/lantern-pharma-announces-first-patient-dosed-in-the-phase-1
4. Study of LP-184 in patients with advanced solid tumors. ClinicalTrials.gov. Updated May 16, 2024. Accessed September 23, 2034. https://clinicaltrials.gov/study/NCT05933265