FDA Clears Phase 1 Pediatric CNS Cancer Trial for STAR-001 Combination Therapy
Key Insights
The FDA has cleared an IND application for STAR-001, a precision oncology compound targeting pediatric CNS malignancies including ATRT (search), DIPG (search), GBM (search), medulloblastoma (search), and ependymoma (search).
The planned Phase 1 trial will evaluate STAR-001 as monotherapy and in combination with spironolactone across 15 leading academic pediatric oncology centers.
Preclinical data shows the STAR-001/spironolactone combination extended median survival by 181% in ATRT (search) models by targeting DNA repair mechanisms.
Lantern Pharma Inc. and its wholly owned subsidiary Starlight Therapeutics (search) announced that the U.S. Food and Drug Administration has cleared the Investigational New Drug application for STAR-001 in a planned Phase 1 pediatric clinical trial (IND No. 179145). The multicenter, open-label, dose escalation study will evaluate STAR-001 as a single agent and in combination with spironolactone in pediatric patients with relapsed or refractory central nervous system malignancies.
The trial represents a significant milestone for pediatric neuro-oncology, targeting some of the most treatment-resistant childhood cancers. STAR-001 is a precision oncology compound whose CNS and pediatric CNS indications were initially identified using Lantern's proprietary RADR AI platform.
Addressing Critical Unmet Medical Need
Pediatric CNS tumors (search) represent one of the most devastating categories of childhood cancer. In the United States, an estimated 4,975 new cases of primary brain tumors will be diagnosed in children and adolescents in 2026 alone, making brain tumors the leading cause of cancer-related death among children and adolescents ages 0 to 19. Globally, approximately 47,600 new pediatric CNS tumor cases are diagnosed each year, resulting in an estimated 23,500 deaths annually.
Despite significant advances in molecular profiling and surgical technique over the past two decades, survival outcomes for children with relapsed or refractory high-grade CNS tumors have improved only marginally. For certain diagnoses, the prognosis remains catastrophic. Diffuse Intrinsic Pontine Glioma (search) (DIPG (search)) carries a median survival of less than 12 months from diagnosis with no approved curative option.
The trial will evaluate STAR-001 across aggressive pediatric CNS malignancies including Atypical Teratoid/Rhabdoid Tumor (search) (ATRT (search)), for which Lantern Pharma holds FDA Rare Pediatric Disease Designation; DIPG (search), a brainstem tumor with virtually no long-term survivors under current standard of care; Glioblastoma (search) (GBM (search)); Medulloblastoma (search); and Ependymoma (search).
Novel Combination Strategy Targets DNA Repair
A scientifically distinctive feature of the planned trial is a dedicated combination cohort evaluating STAR-001 alongside spironolactone, exploiting a biological vulnerability in CNS tumor cells identified through Lantern's RADR AI platform as a novel approach to creating synthetic lethality in brain tumors.
STAR-001 operates through a precision bioactivation mechanism, selectively converted into a potent DNA-crosslinking agent within tumor cells that overexpress PTGR1 (search) (Prostaglandin Reductase 1 (search)). It induces DNA double-strand breaks that are lethal to cancer cells if left unrepaired. Spironolactone removes this repair option by degrading ERCC3 (search).
Lantern's RADR AI platform identified ERCC3 (search) (Excision Repair Cross-Complementation Group 3 (search)), a key helicase in the nucleotide excision repair pathway, as a central repair mechanism that could be exploited in high-grade pediatric CNS malignancies. Spironolactone, a brain-penetrant, orally administered agent with a long safety record in pediatric patients, degrades ERCC3 through targeted proteasomal degradation, reducing ERCC3 protein levels by at least 50% across tumor models.
Promising Preclinical Results
In ATRT (search) orthotopic xenograft models, the combination extended median survival from 27 to 76 days, a 181% improvement over control (p = 0.0018). Comparable results across medulloblastoma (search) and diffuse midline glioma models showed up to a 3- to 5-fold increase in apoptotic cells versus monotherapy (p < 0.0001).
"In ATRT (search) models, the combination extended median survival by 181% compared to the control. We believe this represents a genuinely new way to attack these brain cancers," said Panna Sharma, CEO and President of Lantern Pharma Inc. and Founder and Chairman of Starlight Therapeutics (search).
Multicenter Trial Design
The planned trial will be conducted across approximately 15 leading academic pediatric oncology centers in collaboration with POETIC (search) (Pediatric Oncology Experimental Therapeutics Investigators' Consortium), a multicenter network of 14 institutions including MD Anderson Cancer Center, Memorial Sloan Kettering Cancer Center, and Lucile Packard Children's Hospital at Stanford, spanning the United States, Canada, and Israel.
The trial is designed to enroll approximately 18 to 42 pediatric patients aged 1 to 17 years, subject to obtaining additional funding. POETIC (search)'s established clinical infrastructure provides Starlight with the reach to enroll a geographically and demographically diverse patient population across North America and internationally.
"STAR-001 is a novel, precision brain-penetrant alkylator, bioactivated by PTGR1 (search), that has demonstrated meaningful activity across multiple malignant pediatric brain tumor types in preclinical models," said Marc Chamberlain, M.D., Chief Medical Officer of Starlight Therapeutics (search). "We look forward to initiating this planned trial and to the possibility of delivering a new therapeutic option to children who need it most."
STAR-001 is a precision acylfulvene-based agent engineered to exploit elevated PTGR1 (search) expression in tumor cells. Laboratory observations have demonstrated that PTGR1-mediated bioactivation selectively converts STAR-001 into a highly reactive DNA-crosslinking species within cancer cells, while normal tissues with lower PTGR1 activity are largely spared. LP-184/STAR-001 has received multiple FDA orphan and rare pediatric disease designations and has demonstrated encouraging activity in early-stage clinical and preclinical studies.