LSTA1-GBM-2A: study protocol for an exploratory phase 2a randomised controlled trial evaluating tumour-homing peptide certepetide with temozolomide in glioblastoma multiforme

Abstract

Introduction Glioblastoma multiforme (GBM) is an aggressive primary brain tumour associated with a poor prognosis despite standard-of-care treatment, including surgical resection, radiotherapy and temozolomide (TMZ) chemotherapy. Certepetide (also known as LSTA1, CEND-1) is an investigational tumour-penetrating peptide that facilitates the extravascular delivery and intratumoural penetration of co-administered immune/chemotherapeutics; however, it has not yet been evaluated in clinical trials for the treatment of intracranial malignancies.

Methods and analysis LSTA1-GBM-2A is an exploratory phase 2a, double-blind, placebo-controlled, randomised, proof-of-concept investigator-initiated trial assessing the safety, tolerability and preliminary efficacy of certepetide in combination with standard-of-care TMZ, compared with TMZ with a matching placebo, in subjects with newly diagnosed GBM.

The trial is funded by Lisata Therapeutics, sponsored by Tartu University Hospital and conducted at hospitals in Estonia and Latvia. Subjects are randomised in a 2:1 ratio. Following initial surgery and radiotherapy with concurrent TMZ, the subjects receive intravenous certepetide or placebo alongside six cycles of adjuvant TMZ treatment. The primary endpoint is overall survival. The target number of subjects is 30. The first subject was recruited in January 2024, and accrual is ongoing.

Ethics and dissemination This study was approved by the Republic of Estonia State Agency of Medicines (17 October 2023) and the State Agency of Medicines of the Republic of Latvia (1 February 2024). The results of this study will be published in peer-reviewed journals and reported at academic conferences.

Trial registration number 2023-506813-23-00.