FDA Provides Guidance on Pediatric CNS Cancer Trial

Lantern Pharma has concluded a type C meeting with the US FDA to clarify the regulatory pathway for a planned pediatric clinical trial of its investigational agent, LP-184 (STAR-001).¹ This meeting, conducted through its wholly owned subsidiary Starlight Therapeutics, focused on advancing a trial for central nervous system (CNS) cancers, including atypical teratoid rhabdoid tumor (ATRT), a rare and aggressive childhood brain cancer.

The FDA provided critical guidance on the proposed clinical trial structure, which includes a parallel cohort specifically for ATRT patients. This design is intended to accelerate data collection in this ultra-rare population, addressing the significant unmet need for effective therapies. The agency also confirmed the potential for incorporating spironolactone as a combination agent to enhance the therapeutic effects of LP-184. This feedback aligns with Lantern's strategy to leverage its proprietary computational biology and machine learning platform, RADR, to identify and optimize drug regimens.

"We are thrilled with the constructive dialogue and positive feedback from our type C meeting with the FDA," said Panna Sharma, president and CEO of Lantern Pharma, in a press release. "This guidance not only reinforces our trial design but also highlights the potential of our AI platform, RADR, in identifying and optimizing combination regimens like spironolactone for these devastating pediatric CNS cancers. We remain committed to rapidly advancing this program with the aim of bringing hope to children and families affected by brain cancer."

Mechanism of Action and Clinical Rationale

LP-184 is a next-generation acylfulvene small molecule that functions as a prodrug, preferentially damaging DNA in cancer cells that exhibit specific biomarkers or harbor mutations in DNA damage repair (DDR) pathways. The drug is activated by the enzyme prostaglandin reductase 1 (PTGR1), which is often overexpressed in certain cancers, including those of the CNS. Once activated, LP-184 creates cytotoxic metabolites that form adducts with DNA, leading to irreparable DNA damage and subsequent tumor cell death. Preclinical studies have demonstrated LP-184's ability to cross the blood-brain barrier and show nanomolar potency against various solid tumors, including pediatric and adult brain cancers.

The planned combination with spironolactone is based on preclinical data showing a synergistic effect. Spironolactone induces the degradation of ERCC3, a key protein in the nucleotide excision repair (NER) pathway, which makes cancer cells deficient in DNA repair. This NER deficiency (NERD) makes the cancer cells significantly more sensitive to the DNA damage induced by LP-184. This mechanism of synthetic lethality offers a promising avenue for treating aggressive CNS tumors, where resistance to conventional therapies is a major challenge.

The FDA has previously granted LP-184 rare pediatric disease designations in ATRT, malignant rhabdoid tumors, rhabdomyosarcoma, and hepatoblastoma.²

Last month, the FDA cleared a new clinical trial for LP-184 plus spironolactone in glioblastoma multiforme (GBM).³The planned phase 1b/2a trial is designed to assess the safety, tolerability, and preliminary efficacy of the LP-184 and spironolactone combination in this patient population.

REFERENCES:

1. Lantern Pharma Announces Completion of Type C Meeting with FDA, Providing Clarity on Regulatory Pathway for Pediatric CNS Cancer Trial. News release. Lantern Pharma. September 3, 2025. Accessed September 4, 2025. https://tinyurl.com/4jjrkbst

2. 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. September 23, 2024. Accessed September 4, 2025. https://tinyurl.com/5bxvfzxd

3. Lantern Pharma's Subsidiary, Starlight Therapeutics, Announces U.S. Food and Drug Administration Clearance of IND for Phase Ib/2a Glioblastoma Multiforme (GBM) Trial. News release. Lantern Pharma. August 6, 2025. Accessed September 4, 2025. https://tinyurl.com/v7b9z24u