Phase I, open-label, dose-escalation trial investigating the safety and efficacy of oncolytic virus BI 1821736 in patients with advanced solid tumors.

Abstract

TPS2688 Background: Despite some advances, the need for novel anti-cancer therapies remains high in patients with advanced solid tumors. Although immunotherapy with checkpoint inhibitors is the preferred treatment for several cancer types, a proportion of patients will have non-responsive tumors or develop resistance. Oncolytic viruses have potential as novel immunotherapies, due to their tumor-selectivity and ability to stimulate a systemic anti-tumor immune response. BI 1821736 is a genetically engineered pseudotype variant of VSV-GP encoding an immune-stimulatory cargo. The VSV-GP backbone is a recombinant chimeric vesicular stomatitis virus modified to replace the innate neurotropic G glycoprotein with the non-neurotropic GP glycoprotein from the lymphocytic choriomeningitis virus. BI 1821736 selectively replicates and lyses cells with defective interferon signaling, which is seen particularly in cancer cells. The immune-stimulating cargo leads to T-cell priming and reactivation within the immunosuppressed tumor microenvironment. Preclinical efficacy, toxicology, and environmental safety results support BI 1821736 administration in humans. Methods: 1467-0001 (NCT05839600) is a Phase I, open-label, dose-escalation study evaluating the safety and early efficacy of BI 1821736 in patients with advanced solid tumors. The study is enrolling adult patients who have exhausted available treatment options, with an Eastern Cooperative Oncology Group Performance Status of 0 or 1, ≥1 lesion amenable to biopsy, and adequate organ function. Patients with brain metastases are excluded unless they have completed brain radiotherapy and are asymptomatic. Patients will receive escalating doses of intravenous BI 1821736 for up to 3 months. Dose escalation will be guided by a Bayesian 2-parameter logistic regression model with overdose control (BLRM-EWOC). The primary objective is to determine the maximum tolerated dose (MTD) and/or recommended Phase II dose based on occurrence of dose-limiting toxicities (DLTs) during the MTD evaluation period of the first treatment cycle (Cycle 1; 21 days). Other safety endpoints include the occurrence of DLTs and adverse events during the treatment period. Further objectives include the assessment of BI 1821736 preliminary efficacy, pharmacokinetics, immunogenicity, shedding, and biomarkers. Patients are being recruited from approximately 10 sites across North America and Europe. Enrollment began in May 2023. A total of six patients have received BI 1821736 as of January 29, 2024. Patients are currently being enrolled to dose level 2. Clinical trial information: NCT05839600 .