pharma · Muscle-invasive bladder cancer · Unresectable intrahepatic cholangiocarcinoma
Ningbo Cancer Hospital is a pharma organization headquartered in CN. Primary therapeutic focus areas include Muscle-invasive bladder cancer, Unresectable intrahepatic cholangiocarcinoma, Head and neck squamous cell carci
Phase 3 · small molecule · Glioblastoma
Lomustine (GLEOSTINE) is an oral DNA inhibitor small-molecule chemotherapy approved in the United States and being investigated by Ningbo Cancer Hospital in a Phase 3 randomized controlled trial for glioblastoma at first progression. The EORTC 2227-BTG trial (LEGATO) evaluates lomustine with or without reirradiation in
Internal code EORTC 2227-BTG
Lomustine (GLEOSTINE) is an oral DNA inhibitor small-molecule chemotherapy approved in the United States and being investigated by Ningbo Cancer Hospital in a Phase 3 randomized controlled trial for glioblastoma at first progression. The EORTC 2227-BTG trial (LEGATO) evaluates lomustine with or without reirradiation in this patient population. Lomustine is an established alkylating agent with a long clinical history; the current trial represents a contemporary investigation of its role in combination with radiation therapy for recurrent disease. The program is sponsored by Ningbo Cancer Hospital with no disclosed partner arrangement. Regulatory approval for lomustine already exists in the United States under multiple manufacturers (Azurity and Carnegie), indicating established market presence. The Phase 3 LEGATO trial represents active clinical development to define optimal treatment sequencing and combination strategies in first-progression glioblastoma, a setting with significant unmet medical need.
Glioblastoma remains one of the most aggressive human malignancies with poor prognosis; median overall survival is approximately 15 months despite maximal initial therapy. First progression represents a critical clinical juncture where treatment options are limited and outcomes are particularly poor. The competitive landscape for recurrent glioblastoma includes multiple investigational agents (temozolomide, cediranib, enzastaurin, dendritic cell immunotherapy, and others) alongside established approaches such as stereotactic radiation therapy. Lomustine's potential advantage lies in its oral bioavailability and established safety profile, enabling convenient outpatient administration. The LEGATO trial's investigation of reirradiation combinations addresses a clinically relevant question: whether systemic chemotherapy can be optimized through rational combination with focal radiation. Success in this trial could reposition lomustine as a standard-of-care option for first progression, particularly if the combination approach demonstrates superior efficacy or tolerability compared to monotherapy or competing regimens. The patient population is substantial—thousands of glioblastoma patients progress annually in major markets—and any validated treatment strategy carries significant commercial and clinical value.
Lomustine (GLEOSTINE) is a nitrosourea alkylating agent classified as a DNA inhibitor. It is administered orally, distinguishing it from intravenous chemotherapy agents. The drug acts by cross-linking DNA, leading to cell death through disruption of DNA replication and transcription.
Also known as: GBM, GBM (glioblastoma), WHO grade IV glioma, glioblastoma (disease), glioblastoma multiforme, glioblastoma multiforme (disease)
Prevalence: Point prevalence: 1-9 / 100 000 (Worldwide) — source: Orphanet, validated.
The most malignant astrocytic tumor (WHO grade IV). It is composed of poorly differentiated neoplastic astrocytes and it is characterized by the presence of cellular polymorphism, nuclear atypia, brisk mitotic activity, vascular thrombosis, microvascular proliferation and necrosis. It typically affects adults and is preferentially located in the cerebral hemispheres. It may develop from diffuse astrocytoma WHO grade II or anaplastic astrocytoma (secondary glioblastoma, IDH-mutant), but more frequently, it manifests after a short clinical history de novo, without evidence of a less malignant precursor lesion (primary glioblastoma, IDH- wildtype). (Adapted from WHO)
ClinicalTrials.gov lists 877 registered studies for Glioblastoma (AACT aggregate).
Phase breakdown: NA (252), PHASE2 (223), PHASE1 (206), PHASE1/PHASE2 (86), EARLY_PHASE1 (49), PHASE3 (45), PHASE2/PHASE3 (11), PHASE4 (5)
Common investigational therapies:
Disease data sourced from MONDO Disease Ontology (MONDO:0018177), Orphanet — glioblastoma, NCT00001148, NCT00001171, NCT00009035, NCT00028158, NCT00029783, AACT (ClinicalTrials.gov aggregate), ClinicalTrials.gov, Open Targets Platform (CC BY 4.0).
EORTC 2227-BTG (LEGATO) Phase 3 Active
Randomized Phase 3 trial of lomustine with or without reirradiation for first progression of glioblastoma, sponsored by Ningbo Cancer Hospital.
The glioblastoma recurrence treatment landscape includes multiple competing approaches. Temozolomide (Adaptive Biotechnologies) is an oral alkylating agent in Phase 3 development, representing a direct mechanistic competitor to lomustine. Cediranib (AstraZeneca, Phase 3) targets VEGF signaling. Enzastaurin (Eli Lilly, Phase 3) is a protein kinase inhibitor. Dendritic cell immunotherapy (Northwest Biotherapeutics, Phase 3) and ICT-107 (Chongqing Precision Biotech, Phase 3) represent immunotherapy approaches. Edotecarin (Pfizer, Phase 3) and 131I-TLX-101-003 (Lacuna Pharma, Phase 3) are investigational agents with distinct mechanisms. Stereotactic radiation therapy (GT Biopharma) and GTM-103 (GT Biopharma) represent established and investigational radiation-based approaches. Cediranib, EF-41/KEYNOTE D58 (Novo Nordisk), and MIN-003-1806 (Lacuna Pharma) are also in Phase 3. Lomustine's competitive positioning rests on its oral convenience, established safety database, and potential synergy with reirradiation—a clinically relevant combination not universally represented among competitors. However, the field is crowded with multiple Phase 3 programs, suggesting intense competition for market share in this indication.
| Therapy | Company | Mechanism | Status |
|---|---|---|---|
| IRON OXIDE (E172) | Disc Medicine | small_molecule | approved |
| Stereotactic Radiation Therapy | GT Biopharma | other | approved |
| GTM-103 | GT Biopharma | other | approved |
| ICT-107 | Chongqing Precision Biotech Co., Ltd | mab | phase_3 |
| Temozolomide | Adaptive Biotechnologies Corp | small_molecule | phase_3 |
| Dendritic cell immunotherapy | NORTHWEST BIOTHERAPEUTICS INC | small_molecule | phase_3 |
| 131I-TLX-101-003 | Lacuna Pharma Pty Ltd | small_molecule | phase_3 |
| enzastaurin | Eli Lilly and Company | small_molecule | phase_3 |
| MIN-003-1806 | Lacuna Pharma Pty Ltd | small_molecule | phase_3 |
| Cediranib | AstraZeneca | small_molecule | phase_3 |
| EF-41/KEYNOTE D58 | Novo Nordisk A/S | small_molecule | phase_3 |
| Edotecarin | Pfizer | small_molecule | phase_3 |
| CARMUSTINE | — | Glutathione reductase inhibitor | Approved |
| BEVACIZUMAB | — | Vascular endothelial growth factor A inhibitor | Approved |
| TRABEDERSEN | — | Transforming growth factor beta-2 mRNA antisense inhibitor | Phase 3 |
| TOFACITINIB | — | Janus Kinase (JAK) inhibitor | Phase 3 |
| RINDOPEPIMUT | — | Epidermal growth factor receptor erbB1 vaccine antigen | Phase 3 |
| OMBIPEPIMUT-S | — | Wilms tumor protein vaccine antigen | Phase 3 |
| NIVOLUMAB | — | Programmed cell death protein 1 inhibitor | Phase 3 |
| NIMOTUZUMAB | — | Epidermal growth factor receptor erbB1 inhibitor | Phase 3 |
Additional associated therapies sourced from Open Targets Platform (CC0), linked to NovaPharmaNews drug profiles where matched.
Lomustine (GLEOSTINE) holds approved regulatory status in the United States under two manufacturers: Azurity (ANDA219265) and Carnegie (NDA017588), indicating established market authorization and generic/branded formulations. FDA approval history and specific approval dates are not yet disclosed in available sources. European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA, Japan), and National Medical Products Administration (NMPA, China) approval status is not yet disclosed. The Phase 3 LEGATO trial (NCT identifier 2023-505267-36-00) is the current regulatory pathway for investigating lomustine's efficacy and safety in the first-progression glioblastoma setting, which may support label expansion or new indication approval depending on trial outcomes.
Lomustine is an oral chemotherapy agent approved in the United States for cancer treatment. It is currently being investigated in a Phase 3 trial for glioblastoma at first progression, in combination with or without reirradiation.
Yes, lomustine (GLEOSTINE) is FDA-approved and marketed in the United States by Azurity and Carnegie under application numbers ANDA219265 and NDA017588, respectively.
Lomustine is a DNA inhibitor that acts as an alkylating agent, cross-linking DNA strands to disrupt replication and transcription, leading to cancer cell death.
LEGATO (EORTC 2227-BTG) is a randomized Phase 3 trial sponsored by Ningbo Cancer Hospital investigating lomustine with or without reirradiation in patients with glioblastoma at first progression.
Lomustine is manufactured and marketed in the United States by Azurity and Carnegie under the brand name GLEOSTINE.
The LEGATO trial investigates lomustine for glioblastoma at first progression, evaluating the combination of chemotherapy with or without reirradiation.
Lomustine is administered orally, allowing for convenient outpatient treatment compared to intravenous chemotherapy agents.
Lomustine is in Phase 3 clinical development for glioblastoma at first progression under the LEGATO trial, while the drug itself is already approved for other indications.
Ningbo Cancer Hospital is the sponsor of the EORTC 2227-BTG (LEGATO) Phase 3 trial.
Competitors include temozolomide, cediranib, enzastaurin, dendritic cell immunotherapy, ICT-107, edotecarin, and stereotactic radiation therapy, among others, most in Phase 3 development.
Glioblastoma at first progression carries poor prognosis with limited treatment options and short median survival. New effective therapies, particularly those that can be combined with radiation, are urgently needed.
Lomustine is a nitrosourea alkylating agent that inhibits DNA by cross-linking DNA strands, disrupting cellular replication and leading to apoptosis.
No partner is disclosed for the LEGATO trial; Ningbo Cancer Hospital is listed as the sole sponsor.
The primary target of lomustine is DNA; it acts as a non-selective alkylating agent rather than targeting a specific protein.
The expected timeline for LEGATO results is not yet disclosed; trial completion and data readout dates have not been announced.
The trial enrolls patients with glioblastoma experiencing first progression; specific enrollment numbers and detailed eligibility criteria are not yet disclosed.
LOMUSTINE → Drug → Target → Indication → Company → Trials → Competitors
Strategic Positioning: Ningbo Cancer Hospital's sponsorship of the LEGATO trial suggests institutional commitment to glioblastoma research and potential future commercialization in Asian markets. The absence of a disclosed partner may indicate early-stage commercialization planning or a focus on regional development.
Competitive Implications: The crowded Phase 3 landscape for recurrent glioblastoma means lomustine must demonstrate clear clinical benefit—superior efficacy, improved tolerability, or both—to secure market adoption. The oral route and established safety profile are advantages, but temozolomide already occupies this niche. The reirradiation combination strategy differentiates LEGATO from many competitors and addresses a clinically relevant question.
Future Catalysts: Primary efficacy and safety data from LEGATO will be the critical catalyst. Regulatory interactions with FDA and EMA regarding indication expansion will follow positive Phase 3 results. Potential label expansion to first-progression glioblastoma would represent the major commercial milestone.
Expected Milestones: Trial enrollment completion, interim efficacy analyses, final Phase 3 data readout, and regulatory submissions are anticipated but specific timelines are not yet disclosed.
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Intelligence compiled from public regulatory and clinical sources (FDA, EMA, ClinicalTrials.gov and company disclosures). Figures may be editorial or analyst estimates; verify against primary sources before relying on them.