KEY TAKEAWAYS
- The phase 1 trial aimed to evaluate the safety and early response of VSV-GP IT monotherapy in advanced solid tumor pts.
- The primary endpoint was to determine DLTs.
- The ongoing study indicates VSV-GP’s safety and RP2D determination via IT, IV, and IT+IV, alone or with ezabenlimab.
In animal studies, VSV-GP (BI 1831169) is a specialized oncolytic virus that effectively destroys various solid cancer cell types and triggers adaptive anti-tumor immunity. On the findings from the first human trials Stephane Champiat and his research group presented a report on the early findings focusing on VSV-GP administered directly into tumors intratumorally (IT) for individuals with advanced solid tumors.
In the phase I study, VSV-GP was administered IT intravenously (IV) or IT+IV in two parts. Part 1 involved monotherapy, while Part 2 included a combination with the anti-programmed cell death 1 compound ezabenlimab. VSV-GP was given on Days 1 and 4 of Cycle 1 and Day 1 of Cycles 2–4 (21-day cycles). The dose-finding followed the Bayesian Optimal Interval design.
The primary endpoint was the occurrence of dose-limiting toxicities (DLTs) during the maximum tolerated dose (MTD) evaluation period to establish the MTD and/or recommended Phase II dose (RP2D).
About 8 patients underwent VSV-GP monotherapy IT administration—four at dose level (DL) 1 (5 x 107 TCID50) and four at DL2 (5 x 108 TCID50). At DL1, all patients ceased treatment (progressive disease n=3, unrelated Grade [G] 3 E. coli sepsis n=1). DL2 experienced a G1 cytokine release syndrome (fever and low oxygen saturation) after the first dose in one patient.
The maximum cycles received was three. At DL2, one patient discontinued due to G3 neutropenia, and three patients continued. Per protocol, DLT (G3 fatigue) occurred at DL2, and three more patients will be recruited. Common related adverse events (AEs) included pyrexia, chills, and decreased lymphocytes.
The study is ongoing and evaluating the safety and determining RP2D of VSV-GP, administered via IT, IV, and combined IT+IV routes. The investigation is extending to both monotherapy and combination with ezabenlimab, with findings expected to contribute valuable insights into the potential applications of VSV-GP in the clinical setting. Further study will analyze safety, efficacy, pharmacokinetics, shedding, and immunogenicity to evaluate results.
This study is sponsored by Boehringer Ingelheim.
Source: https://cslide.ctimeetingtech.com/immuno23hybrid/attendee/confcal/show/session/34
Clinical Trial: https://clinicaltrials.gov/study/NCT05155332
Champiat S, et al. “First-in-human results from a Phase I dose-escalation study of VSV-GP (BI 1831169) in patients with advanced solid tumors”. Presented at ESMO IO 2023. (Abstract: 137P).
