487P - Induction of an inflammatory tumor microenvironment with oncolytic virus CF33-hNIS-antiPD-L1 intratumoral injection in patients with metastatic triple-negative breast cancer (mTNBC)

Background

CF33-hNIS-anti-PD-L1 (CHECKvacc) is a novel chimeric orthopoxvirus with robust anti-cancer activity in TNBC xenografts. CHECKvacc increased CD8+ T cell infiltration and favorably modulated the tumor microenvironment (TME) in xenograft models. Here we report data from the ongoing first-in-human clinical trial of CHECKvacc intratumoral (IT) injections in patients with mTNBC.

Methods

This is a phase I, single center, single arm trial of CHECKvacc IT. Eligibility criteria include patients with mTNBC that progressed on ≥ 2 chemotherapy regimens and have at least 1 tumor amenable to IT injections. Patients receive CHECKvacc IT at 1 of 8 assigned escalating dose levels on Days 1 and 15 of each 28-day cycle for 3 cycles. Primary objective is to evaluate safety and tolerability. Secondary objectives are to determine recommended phase II dose and efficacy. Exploratory objectives include assessment of TME immune modulation. Formalin fixed tissue biopsies were assessed by multiplex immunofluorescence for CD3, CD8, PD-L1, and pan-cytokeratin and digitally quantified for densities of immune phenotypes. PD-L1 expression was also assessed by a pathologist for a combined positive score (CPS).

Results

From October 2021 to December 2022, 8 patients were enrolled in this ongoing study and received ≥1 dose of CHECKvacc at 1 of the first 3 dose levels (1x105, 3x105, 1x106 PFU). There were no dose limiting toxicities. Six patients had evaluable baseline and post-treatment tissues for immune quantification. From baseline to cycle 1 day 2, CD8+ T cells in the TME increased in 5 of 6 patients (median increase: 34%; range: 9-251%). CD4+ T cells increased in 4 of 6 patients (median increase: 39%; range: 23-73%). PD-L1 expression by CPS increased in 5 of 6 patients (range of increase: 4-50%; p=0.063 by Wilcoxon signed-rank test).

Conclusions

CHECKvacc induces tumor infiltration of CD4+ and CD8+ T cells. Upregulation of PD-L1 within the TME further suggests immune activation by CHECKvacc. The clinical trial is ongoing to further assess dose escalation, tumor response, and the potential for future combination trials with systemic therapies, such as checkpoint blockade and chemotherapy.

Clinical trial identification

NCT05081492.

Editorial acknowledgement

Legal entity responsible for the study

City of Hope Comprehensive Cancer Center.

Funding

Imugene Limited.

Disclosure

B. Modi: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck, Regeneron, Sanofi Genzyme. L.O. Chong, A. Seiz, G. Selvaggi, N. Ede: Financial Interests, Personal, Full or part-time Employment: Imugene Limited. Y. Fong: Financial Interests, Personal, Stocks/Shares: XDemics Corporation, Theromics, Vergent Biosciences, Eureka Biologics; Financial Interests, Personal, Speaker, Consultant, Advisor: Covidien, Iovance Biotherapeutics, Sangamo Therapeutics, University of Alabama Birmingham; Financial Interests, Personal, Advisory Board: Imugene Limited. Y. Yuan: Financial Interests, Personal, Research Funding: Merck, Eisai, Novartis, Puma, Genentech, Celgene; Financial Interests, Personal, Speaker, Consultant, Advisor: Pfizer, Gilead; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Merck, Genentech, Daiichi Sankyo, Immunomedics. All other authors have declared no conflicts of interest.