On August 6, 2025 Starlight Therapeutics, a wholly owned subsidiary of Lantern Pharma Inc. (NASDAQ: LTRN), reported that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for a Phase Ib/2a clinical trial to evaluate STAR-001 (LP-184) in combination with spironolactone for patients with glioblastoma multiforme (GBM) at first progression (Press release, Lantern Pharma, AUG 6, 2025, View Source;Food-and-Drug-Administration-Clearance-of-IND-for-Phase-Ib2a-Glioblastoma-Multiforme-GBM-Trial/default.aspx [SID1234654883]).

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The planned Phase Ib/2a clinical trial (IND 178511) is designed to investigate the safety, tolerability, and preliminary efficacy of STAR-001 in combination with spironolactone in patients with recurrent GBM, one of the deadliest and most aggressive forms of brain cancer. GBM represents approximately 15% of all brain tumors and has a median survival of approximately 12 months from initial diagnosis, with fewer than 5% of patients surviving beyond five years.

"This FDA clearance represents a significant milestone for Starlight Therapeutics and our mission to bring innovative treatment options to patients facing the most challenging forms of brain and CNS cancers," said Dr. Marc Chamberlain, Chief Medical Officer of Starlight Therapeutics. "GBM remains one of the most difficult cancers to treat, with virtually no meaningful therapeutic advances in nearly 17 years. We believe our unique combination approach has the potential to offer new hope for patients and their families while advancing a novel mechanism to challenge these recurrent brain cancers."

Targeting GBM Through Innovative Synthetic Lethality

STAR-001 (also referred to as LP-184 when focused on other solid tumor indications) is a synthetically lethal, brain-penetrant, novel DNA-damaging agent that has demonstrated promising preclinical activity against various solid tumors, including pediatric and adult brain cancers. Lantern Pharma has previously been awarded both FDA Orphan Drug Designation and FDA Fast Track Designation for STAR-001 in GBM, underscoring the significant unmet medical need and the drug’s potential to address it. An existing Phase 1a trial to determine safety, dosing, the maximum tolerated dose (MTD) and tolerability across a range of solid tumors, including GBM, is currently underway and expected to complete enrollment in the current quarter. This trial is expected to help establish a baseline dosing level and expectations of drug-concentration in tumor and plasma for future clinical trials, including those being planned by Starlight Therapeutics.

The combination of STAR-001 with spironolactone, an existing FDA approved drug, represents a scientifically rational approach to treating GBM. STAR-001 is a blood-brain barrier permeable small molecule that leverages synthetic lethality to exploit DNA damage repair (DDR) deficiencies, particularly those overexpressing PTGR1. Approximately 60% of GBM cells overexpress PTGR1 levels sufficient to activate STAR-001. Spironolactone significantly enhances this therapeutic effect by inducing degradation of ERCC3, a critical protein involved in nucleotide excision repair (NER). This mechanism leads to NER deficiency (NERD), making GBM cells significantly more sensitive to STAR-001 and less capable of repairing the DNA damage caused by the administration of STAR-001. This synergistic approach is particularly promising in GBM which has often become resistant to therapies in the recurrent setting.

AI-Driven Drug Development Platform

Starlight Therapeutics was formed to pursue the focused clinical development of central nervous system (CNS) oncology indications developed and advanced through Lantern Pharma’s proprietary artificial intelligence drug development platform, RADR. This AI-driven approach enables the identification of optimal drug-cancer combinations and patient populations most likely to benefit from treatment, significantly reducing the time and cost typically associated with traditional drug development.

"The clearance of this IND demonstrates the power of our efficient, data-driven drug development model in identifying promising therapeutic opportunities in areas of high unmet medical need," said Panna Sharma, President and CEO of Lantern Pharma. "Through Starlight Therapeutics, we are positioned to dedicate focused resources and expertise to advancing treatments for some of the most challenging cancers affecting the brain and central nervous system in both adults and children, while developing meaningful therapies that can reach patients in an accelerated timeline compared to traditional drug development processes."

Market Opportunity and Next Steps

With GBM representing an annual market opportunity of $3 to $5 billion globally and case numbers accelerating worldwide, there is an urgent need for innovative treatment approaches. The current standard of care has remained largely unchanged for over 15 years, highlighting the critical importance of novel therapeutic strategies like the STAR-001 combination.

Starlight is targeting commencement of the Phase Ib/2a trial in late 2025 or early 2026, subject to additional funding, and plans to provide regular updates on trial preparation, patient enrollment progress, and preliminary data as they become available.

About Glioblastoma Multiforme (GBM)

Glioblastoma multiforme is the most common and aggressive form of primary brain tumor in adults, accounting for approximately 15% of all brain tumors. Despite aggressive multimodal treatment including surgery, radiation, and chemotherapy, the prognosis remains extremely poor, with a median survival of only 12 months and a five-year survival rate of less than 5%. The blood-brain barrier presents a significant challenge in treating GBM, as most therapeutic agents cannot effectively penetrate brain tissue.