FDA Clears Novel Combination Trial for Recurrent Glioblastoma

A new clinical trial for patients with recurrent glioblastoma multiforme (GBM), a notoriously difficult-to-treat and aggressive form of brain cancer, has received clearance from the US FDA.¹

Starlight Therapeutics, a subsidiary of Lantern Pharma, announced that its investigational new drug application for a phase Ib/2a clinical trial evaluating the combination of the novel agent STAR-001 (LP-184) with the FDA-approved drug spironolactone has been cleared. The trial will focus on adult patients whose GBM has progressed after initial treatment.

Glioblastoma, which accounts for approximately 15% of all brain tumors, has seen few therapeutic advancements in recent years, with the current standard of care remaining largely unchanged for over 15 years. The median survival for patients with GBM is approximately 12 months from initial diagnosis, with a 5-year survival rate of less than 5%. The challenging nature of treating GBM is compounded by the blood-brain barrier, which limits the effectiveness of many therapeutic agents.

The planned phase 1b/2a trial is designed to assess the safety, tolerability, and preliminary efficacy of the STAR-001 and spironolactone combination in this patient population.

"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 [central nervous system (CNS)] cancers," said Marc Chamberlain, MD, chief medical officer of Starlight Therapeutics, in a press release. "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."

The therapeutic strategy leverages a concept known as synthetic lethality. STAR-001 is a brain-penetrant, DNA-damaging agent that targets DNA damage repair deficiencies. Its mechanism of action is particularly effective in GBM cells that overexpress the PTGR1 protein, which are estimated to constitute about 60% of GBM cases. Spironolactone, a widely used diuretic, acts synergistically with STAR-001 by inducing the degradation of ERCC3, a protein crucial for nucleotide excision repair (NER). This action leads to NER deficiency, a state in which cancer cells are more sensitive to the DNA damage caused by STAR-001 and less capable of repairing it. This dual-pronged approach is particularly promising for recurrent GBM, which often develops resistance to previous therapies.

The clinical development of STAR-001 is supported by Lantern Pharma's proprietary AI-driven drug development platform, RADR®. This platform utilizes machine learning and genomics to identify optimal drug-cancer combinations and patient populations most likely to benefit, aiming to accelerate the drug development timeline.

The company has previously received both FDA orphan drug and fast track designations for STAR-001 in GBM, reflecting the urgency and potential of this new therapeutic strategy.²

The phase 1b/2a trial is anticipated to commence in late 2025 or early 2026, contingent on additional funding. Its design will build upon an ongoing phase 1a trial (NCT05933265) evaluating the safety, dosing, and maximum tolerated dose of STAR-001 as a monotherapy in patients with a variety of advanced solid tumors, including GBM. This earlier trial is expected to provide critical pharmacokinetic data to inform the dosing for the combination study.³

REFERENCES:

1. 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 August 7, 2025. https://tinyurl.com/v7b9z24u

2. 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 August 6, 2025. https://tinyurl.com/5n7devsu

3. Study of LP-184 in Patients With Advanced Solid Tumors. ClinicalTrials.gov. Updated March 6, 2025. Accessed August 7, 2025. https://www.clinicaltrials.gov/study/NCT05933265