On November 10, 2026 Lantern Pharma Inc. (NASDAQ: LTRN), a clinical-stage AI-driven precision oncology company, and its wholly owned subsidiary Starlight Therapeutics reported the publication of Phase 1a clinical data for LP-184 (zirdafulven) in patients with recurrent GBM. LP-184 is being developed as STAR-001 for central nervous system (CNS) cancers. The paper appears in the October 2026 issue of Cancer Research Communications, a peer-reviewed journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper). The work was led by investigators at Johns Hopkins University School of Medicine, the Sidney Kimmel Comprehensive Cancer Center and the Hugo W. Moser Research Institute at Kennedy Krieger, together with Lantern scientists.
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The study shows that LP-184 is generally well tolerated in patients with recurrent GBM and defines the path forward. Plasma levels at the RDE reached projected effective systemic exposures. However, only about 20% of systemic drug is expected to reach brain tumors, so single-agent concentrations of LP-184 in the brain tumor are not projected to remain at therapeutic levels for a sustained period. Spironolactone is an FDA-approved, brain-penetrant drug used primarily to treat hypertension and as a diuretic. It also triggers degradation of ERCC3, a key protein in the DNA repair pathway GBM cells use to survive DNA-damaging agents like LP-184. In preclinical models, spironolactone lowers the concentration of LP-184 needed to kill GBM cells 3- to 6-fold. Together, these findings provide the dosing basis for the planned Phase 1b/2a trial in GBM at first recurrence.
Key Findings from the Phase 1a GBM Cohort
Patient population: All 16 patients had IDH wild-type, WHO grade 4 GBM previously treated with surgery, radiation and temozolomide (TMZ), with a median of two prior lines of therapy. Of the 14 with known status, 8 (57%) had an unmethylated MGMT promoter, a common driver of TMZ resistance.
Safety and tolerability: The safety profile in patients with GBM was consistent with the broader solid tumor population, and no adverse events occurred only in patients with GBM. Nausea was grade 1 to 2 in all affected patients, and severe thrombocytopenia and transaminitis were infrequent. The two grade 3 to 4 liver enzyme elevations both occurred at the highest dose level tested, above the RDE.
Recommended dose for expansion: The RDE is 0.39 mg/kg, given intravenously on days 1 and 8 of each 21-day cycle. It was established based on the totality of safety and pharmacokinetic data.
PTGR1 biomarker: Lantern developed an RT-qPCR assay to measure PTGR1, the enzyme that activates LP-184 inside tumor cells, and defined an expression threshold associated with LP-184 sensitivity. Six of eight (75%) available pretreatment tumor samples exceeded that threshold, consistent with published reports of PTGR1 overexpression in more than 70% of GBM.
Clinical observations: Consistent with the projected limited brain exposure of LP-184 as a single agent, no objective radiographic responses were observed. One patient with MGMT-methylated GBM at first recurrence received LP-184 for six months. That patient has remained clinically and radiographically stable for more than 22 months after enrollment, including more than 17 months off treatment, without further therapy.
Rationale for the LP-184 Plus Spironolactone Combination
Treatment failure in GBM is driven by two problems: too little drug reaching the tumor, and DNA repair that lets tumor cells survive the drug that does. The combination is designed to address both.
A mechanism that bypasses MGMT. LP-184 alkylates DNA at a different site than TMZ or lomustine. The resulting lesions are not repaired by MGMT, the main cause of TMZ resistance. They are instead resolved primarily through transcription-coupled nucleotide excision repair (TC-NER).
Spironolactone shuts down that repair pathway. Spironolactone, a widely used FDA-approved medicine that crosses the blood-brain barrier, triggers degradation of ERCC3 (XPB), a core TC-NER protein. Across multiple patient-derived GBM cell models, spironolactone lowers the concentration of LP-184 needed to kill tumor cells 3- to 6-fold.
A defined dosing schedule. In orthotopic GBM xenografts, tumor ERCC3 reached its lowest level 8 hours after a dose of spironolactone. Three daily doses reduced tumor ERCC3 by approximately 80%, compared with 49% to 57% after one or two doses. Spironolactone did not reduce ERCC3 in the liver, suggesting the effect is concentrated in tumor tissue.
Greater tumor cell killing. Giving LP-184 8 hours after the third daily dose of spironolactone approximately doubled tumor cell death, measured by cleaved caspase-3, compared with LP-184 alone.
A bridge from patient pharmacokinetics to tumor exposure. Pharmacokinetic modeling used plasma data from 11 patients treated at the RDE. It projects that adding spironolactone will bring intratumoral LP-184 to approximately 2- to 3-fold above the concentration needed to kill GBM cells.
The combination was identified with support from Lantern’s RADR AI platform. RADR also points to DNA damage repair deficiencies and EGFR alterations, both common in GBM, as predictors of LP-184 sensitivity.
"Glioblastoma is especially difficult to treat because a therapy must both reach the brain at effective levels and overcome the tumor’s ability to repair the damage," said Reginald Ewesuedo, M.D., MBA, Vice President of Clinical Development at Lantern Pharma. "This study shows LP-184 is well tolerated in patients with recurrent GBM and points directly to how we can improve its activity in the tumor. By removing a key DNA repair protein with spironolactone, we aim to make the LP-184 that reaches the tumor considerably more effective."
"Limited brain exposure is why many drugs fail in glioblastoma, and this paper is direct about that challenge and specific about the answer," said Panna Sharma, President and CEO of Lantern Pharma. "Rather than push the dose higher, we used patient pharmacokinetic data, insights from our RADR AI platform and our collaborators’ models at Johns Hopkins to design a combination that makes the drug reaching the tumor work harder. We now have a defined dose and schedule to carry into the planned Phase 1b/2a study with our CNS-focused subsidiary, Starlight Therapeutics."
Next Steps
The planned Phase 1b/2a study (NCT07431216) is sponsored by Starlight Therapeutics under an FDA-cleared Investigational New Drug application. It is designed to evaluate the safety, pharmacokinetics and objective response of LP-184 (STAR-001) plus spironolactone in patients with supratentorial GBM at first recurrence after standard TMZ-based therapy. The completed Phase 1a study is registered as NCT05933265.
Lantern Pharma funded the clinical trial and preclinical studies.
About the Publication
Schreck KC, Lal B, Zhou J, Lopez-Bertoni H, Holdhoff M, Ewesuedo R, Bhatia K, Chamberlain M, Laterra J. "Phase Ia Evaluation of LP-184 in Recurrent Glioblastoma: Safety, Pharmacokinetics, and Translational Optimization of CNS Exposure." Cancer Research Communications. 2026;6(10):2519–2528. DOI: 10.1158/2767-9764.CRC-26-0518.
About LP-184 (STAR-001)
LP-184 (zirdafulven) is a novel small molecule acylfulvene prodrug designed to damage DNA selectively in tumor cells. It is activated by PTGR1, an enzyme overexpressed in many solid tumors, including GBM. It is especially active in tumors with deficiencies in DNA damage repair. The DNA lesions LP-184 creates are independent of MGMT status. LP-184 has received FDA Fast Track Designation for GBM and triple-negative breast cancer (TNBC). It has also received FDA Orphan Drug Designations, including for malignant gliomas and atypical teratoid rhabdoid tumors (ATRT). LP-184 is being developed as STAR-001 for CNS cancers through Starlight Therapeutics.
(Press release, Lantern Pharma, NOV 10, 2026, View Source [SID1234674590])