Lantern Pharma's Stralight Therapeutics Publishes LP-184 Phase 1a GBM Data, Establishing The Recommended Dose For Expansion And A Clinically Translatable Dosing Strategy For The Planned Phase 1b/2a Trial

Publication in Cancer Research Communications establishes the recommended dose for expansion and a clinically translatable dosing strategy for the planned Phase 1b/2a trial (NCT07431216)

• LP-184 was generally well tolerated in 16 heavily pretreated patients with recurrent glioblastoma (GBM) enrolled in a 63-patient Phase 1a study in advanced solid tumors, which established the recommended dose for expansion (RDE)
• In orthotopic GBM patient-derived xenograft models, three daily doses of spironolactone reduced tumor levels of the DNA repair protein ERCC3 by approximately 80% and approximately doubled LP-184-induced tumor cell death
• Pharmacokinetic modeling based on clinical data from Phase 1a patients projects that LP-184 at the RDE, combined with spironolactone, will reach intratumoral concentrations approximately 2- to 3-fold above those needed to kill GBM cells

Lantern Pharma Inc. (NASDAQ:LTRN), a clinical-stage AI-driven precision oncology company, and its wholly owned subsidiary Starlight Therapeutics today announced 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. 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.

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.

1. 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).
2. 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.
3. 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.
4. 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.
5. 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.