A Phase 1b/2a Study to Evaluate the Safety, Pharmacokinetics, and Objective Response of STAR-001 (LP-184) in Combination With Spironolactone in Supratentorial Glioblastoma at First Progression

NCT07431216 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: STAR001-GBM25-01
• Study Type: interventional
• Target: 68
• Locations: 0 countries
• Sites: N/A

Brief Summary

Approximately 58-68 total subjects will be enrolled. In the first stage, 10 response evaluable subjects (either IDHwt or IDHm Grade 4 astrocytoma) will be enrolled. If 1 or more of the first 10 response evaluable subjects achieve an objective response, 19 further subjects may be accrued in the second stage (for a total of 29 response evaluable subjects). Subjects enrolling in the study will provide fresh (in subjects who undergo a planned tumor resection) or archival (all subjects) tumor tissue sample (at least 10 unstained slides of 5-micron thickness) at screening for retrospective exploratory biomarker analysis and determination of intertumoral PTGR1 levels. STAR-001 (LP-184) will be administered via IV infusion over 30 minutes on Day 1 and Day 8 of each 21-day cycle. The STAR-001 dose for this study is 0.39 mg/kg. Spironolactone will be administered orally on Day (-2), Day (-1), and between 4-8 hours before the STAR-001 infusion on D1 (Day of STAR-001 IV infusion) and on Day 6, Day 7, and between 4-8 hours before the STAR-001 infusion on Day 8 . The spironolactone dose for this study is 100 mg given 3 times prior to STAR-001 infusion.

Conditions

Glioblastoma (GBM)

Keywords

recurrent GBM; rGBM

Outcome Measures

Primary Outcomes (1)

• To evaluate the safety and tolerability of STAR-001 (LP-184) when administered with spironolactone in subjects with recurrent IDHwt glioblastoma or IDHm Grade 4 astrocytoma.

  Incidence and severity of adverse events (AEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0

  2 years

Study Arms (2)

10 subjects in the IDHwt arm

EXPERIMENTAL

If, among the first 10 enrolled participants in the IDHwt arm, at least 1 subject achieves an objective response, an additional 19 subjects will be enrolled in that arm. Spironolactone is administered with each STAR-001 infusion.

Drug: STAR-001 (LP-184) will be administered via IV infusion over 30 (± 5) minutes on Day 1 and Day 8 of each 21-day cycle.; Drug: Spironolactone (drug)

10 subjects in the IDHm Grade 4 astrocytoma arm

EXPERIMENTAL

If, among the first 10 enrolled participants in the IDHm Grade 4 astrocytoma arm, at least 1 subject achieves an objective response, an additional 19 subjects will be enrolled in that arm.

Drug: STAR-001 (LP-184) will be administered via IV infusion over 30 (± 5) minutes on Day 1 and Day 8 of each 21-day cycle.; Drug: Spironolactone (drug)

Interventions

STAR-001 (LP-184) will be administered via IV infusion over 30 (± 5) minutes on Day 1 and Day 8 of each 21-day cycle. DRUG

The current study treatment will use STAR-001 in combination with the oral diuretic spironolactone. In preclinical tumor models, co-treatment with spironolactone (SP), a transcription-coupled nucleotide excision repair (TC-NER) inhibitor, sensitized GBM cells and xenografts to STAR-001(LP-184).

10 subjects in the IDHm Grade 4 astrocytoma arm; 10 subjects in the IDHwt arm

Spironolactone (drug) DRUG

Spironolactone will be administered orally upon awakening taken without food on Day -2, Day -1 and Day 1 (4-8 hours prior to the STAR-001 infusion) and on Day 6, Day 7, and on Day 8.

Also known as: Spironolactone

10 subjects in the IDHm Grade 4 astrocytoma arm; 10 subjects in the IDHwt arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histopathology confirmed supratentorial GBM at first recurrence including both IDHwt GBM and IDHm Grade 4 astrocytoma.
• Provision of archival tissue and in re-resected subjects, contemporaneous tissue.
• No more than one prior systemic treatment (temozolomide + involved field radiotherapy +/- an experimental agent +/- tumor treating fields device) in IDHwt GBM
• No more than one prior systemic therapy following diagnosis of IDHm Grade 4 astrocytoma
• Radiographically measurable disease that can be assessed per RANO 2.0.
• Subjects are ≥ 18 and \< 70 years old at the time of informed consent with a diagnosis of progressive or recurrent GBM by MRI findings.
• Up to 5 subjects in each Simon stage have a clinically indicated need for surgical intervention per institutional standard of care.
• Performance status must be ≥ 70% on the Karnofsky scale within 14 days prior to enrolment.
• Subjects on a stable or decreasing dose of systemic corticosteroid regimen (no increase for 7 days and dexamethasone dose or equivalent steroid dose \< 4 mg/day) prior to baseline screening MRI are allowed. Exception is for subjects undergoing planned tumor resection where the dexamethasone dose may be temporarily increased and subsequently tapered as clinically indicated.
• Subject has adequate organ function, defined as follows:
• Note: Complete blood count should be obtained without transfusion or receipt of colony-stimulating factors in the 2 weeks before obtaining a sample.
• absolute neutrophil count ≥1,000/μL
• platelets ≥100,000/μL
• haemoglobin ≥ 8 g/dL
• serum creatinine clearance ≥60 mL/min

You may not qualify if:

• Any radiation therapy within 12 weeks prior to the first dose of study drug. unless the progression is clearly outside the radiation field (e.g., beyond the high-dose region or 80% isodose line) or there is pathologic confirmation of disease progression.
• Subject has received more than 1 systemic therapy.
• Subject has known hypersensitivity to STAR-001 (LP-184) or spironolactone, their components, or their excipients.
• Subjects had a known additional malignancy that progressed or required active treatment within the last 2 years. Exceptions include treated basal cell or localized squamous cell skin carcinoma, localized prostate cancer, or other localized carcinomas such as carcinoma in situ of cervix, breast, or bladder.
• Subject is considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease, or active infection that requires systemic therapy. Specific examples include, but are not limited to, history of (non-infectious) pneumonitis that required steroids or current pneumonitis, uncontrolled ventricular arrhythmia, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study (including obtaining consent).
• Subject has a condition (such as transfusion-dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results or interfere with the subject's participation for the full duration of the study treatment including the following:
• a. Subjects who received colony-stimulating factors (e.g., granulocyte-colony stimulating factor, granulocyte-macrophage colony-stimulating factor, or recombinant erythropoietin) within 2 weeks prior to the first dose of study drug are not eligible.
• Subject has a known history of HIV (type 1 or 2 antibodies).
• Subject has known active hepatitis B (e.g., hepatitis B surface antigen reactive) or hepatitis C (e.g., hepatitis C virus ribonucleic acid \[qualitative\] is detected). Subjects with treated hepatitis C are permitted.
• Subject is currently participating and receiving an investigational agent.
• Subject has not recovered (i.e., to Grade ≤1 or to baseline) from cytotoxic therapy-induced adverse events (AEs). Note: Subjects with Grade ≤2 neuropathy, Grade ≤2 alopecia, or Grade ≤2 fatigue is an exception to this criterion and qualify for the study.
• Subject had treatment with prior systemic anticancer therapy within the 4 weeks prior to the first dose of study drug, or
• Subject has received a live vaccine within 14 days of planned start of study drug.
• Subject has clinically significant cardiovascular disease (e.g., significant cardiac conduction abnormalities, uncontrolled hypertension, cardiac arrhythmia or unstable angina, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, and history of cerebrovascular accident) within 3 months prior to screening.
• Subject has heart rate-corrected QT interval prolongation \>480 ms (average of triplicate ECGs) by Fredericia at screening except for a documented bundle branch block or unless secondary to pacemaker. In the case of a documented bundle branch block or a pacemaker, discussion with the medical monitor is required prior to enrolment.

Sponsors & Collaborators

• Starlight Therapeutics Inc.: lead

Related Links

• Starlight Therapeutic is a precision oncology company focused solely on CNS (central nervous system) cancers, primarily brain cancers, which comprise a large and growing market globally.

MeSH Terms

Conditions

Glioblastoma

Interventions

Spironolactone; Pharmaceutical Preparations

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Marc M.D. Chamberlain, MD

  Starlight Therapeutics Inc.

  STUDY DIRECTOR

Central Study Contacts

Sandra Sinclair, MHA/Ed, RN

CONTACT

832.622.1699; sandra@lanternpharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Allowed are subjects who undergo planned tumor resection as per institutional standard of care practice. These subjects will start treatment with the combination of STAR-001 (LP-184) and spironolactone 7-20 days post-surgery. Between 10-15 subjects will enroll in each of two arms (patients with IDH wildtype \[IDHwt\] primary GBM and patients with IDH mutated \[IDHm\] Grade 4 astrocytoma) including subjects that undergo a planned tumor resection. Ten radiographically evaluable subjects in each arm are required to determine the objective response per the Simon 2-stage design. In subjects undergoing a planned tumor resection, residual tumor that is measurable by RANO 2.0 criteria are evaluable for radiographic response. Subjects not undergoing planned tumor resection must have measurable disease to enroll per RANO 2.0. In the first stage, 10 response evaluable subjects (either IDHwt or IDHm Grade 4 astrocytoma) will be enrolled. If 1 or more of the first 10 response evaluable subjects ac

Study Record Dates

• First Submitted: February 18, 2026
• First Posted: February 24, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share