CLARITY-GBM: A phase II, multi-centered, open-label, single-arm study to evaluate the safety and efficacy of cetuximab and lomustine (CCNU) in adult patients with recurrent high-grade glioblastoma.

Abstract

TPS2095 Background: Recurrent glioblastoma (GBM) has a poor prognosis with no universally accepted systemic standard of care. Lomustine (CCNU) remains a commonly used benchmark, achieving 6-month progression-free survival (PFS-6) rates of approximately 20%. Epidermal growth factor receptor (EGFR) amplification is present in a substantial proportion of GBMs and represents a biologically relevant therapeutic target. Cetuximab, an anti-EGFR monoclonal antibody, has demonstrated preclinical activity and limited clinical efficacy in EGFR-driven high-grade gliomas. CLARITY-GBM evaluates the safety and preliminary efficacy of combining cetuximab with lomustine in adults with recurrent high-grade glioblastoma. Methods: CLARITY-GBM is a prospective, open-label, multicenter, single-arm Phase II study conducted at four tertiary cancer centres in India. Eligible patients are adults (≥18 yrs) with histologically confirmed WHO grade 4 glioblastoma at first or second recurrence following standard chemoradiation, ECOG performance status 0–2, and measurable disease per RANO criteria. Participants will receive cetuximab intravenously 500 mg/m² every 2 weeks in combination with oral lomustine 110 mg/m² every 6 weeks. Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision. Tumour assessments are performed every 6 weeks using MRI and evaluated according to RANO criteria. The study uses an exact single-stage Phase II design testing the null hypothesis that PFS-6 ≤20% versus the alternative hypothesis that PFS-6 ≥40%, with a one-sided alpha of 0.10 and 80% power. A total sample size of 25 patients is planned to ensure 24 evaluable patients for the primary analysis. The regimen will be considered promising if at least 8 patients are progression-free at 6 months. A single interim futility analysis is planned after 15 evaluable patients. The primary endpoint is PFS-6. Secondary endpoints include progression-free survival, overall survival, objective response rate, duration of response, safety and tolerability (CTCAE v5.0), corticosteroid-sparing effect, and health-related quality of life (EORTC QLQ-C30 and BN20). Exploratory analyses evaluate correlations with EGFR amplification, EGFRvIII status, and MGMT promoter methylation. Clinical trial information: CTRI/2026/01/100794. Design and key methodological features of the CLARITY-GBM trial. Characteristic Description Study Design Phase II, open-label, single-arm Population Adults with recurrent WHO grade 4 GBM Sample Size 25 planned (24 evaluable) Treatment Cetuximab q2w + Lomustine q6w Primary Endpoint PFS-6 Statistical Design One-sample exact binomial Null/Alternative PFS-6 ≤20% vs ≥40% Power/Alpha 80%, one-sided 0.10 Interim Analysis After 15 evaluable patients Exploratory Biomarkers EGFR, EGFRvIII, MGMT