1048P - Phase I/II Study of JK08, an IL-15 antibody fusion protein targeting CTLA-4, with unresectable locally advanced or metastatic cancer

Background

CTLA-4 is a central inhibitory regulator of T-cell activation & a hallmark of T-regulatory cells (Tregs). Emerging evidence suggests anti-tumor activity of CTLA-4 antibodies may be modulated by the local presence of NK cells, which can mediate Treg depletion. IL-15 is a pleiotropic cytokine important in both innate & adaptive immunity. The IL-15/IL-15Rα complex can stimulate adjacent cells through the IL-2Rβ/γ complex, with the highest expression on NK cells & CD8+ T cells. JK08, a fully human monoclonal antibody specific for CTLA-4 with a C-terminal fusion consisting of IL-15/IL-15Rα, is intended to widen the therapeutic window for CTLA-4-targeted therapy & IL-15 targeted therapy. Preclinical studies demonstrate JK08 retains the functionality of the CTLA-4 antibody & the IL-15 fusion domain.

Methods

Patients (pts) with relapsed/refractory solid tumors receive subcutaneous (SQ) JK08 monotherapy once weekly in this phase 1/2 accelerated 3+3 dose escalation study. Pts are evaluated for safety and anti-tumor activity. Secondary endpoints include evaluation of pharmacokinetic parameters & immunogenicity. Exploratory endpoints include PK, proliferation & activation markers of immune cell populations, & changes in cytokine levels. Four expansion cohorts are planned following dose escalation.

Results

Eighteen (18) refractory metastatic solid tumor pts have been treated to date with JK08. A maximal tolerated dose has not been reached. Median (range) age: 66.5 (53 - 80) years. To date, treatment has been well-tolerated, with adverse events consisting primarily of Gr 1 & 2 injection site reactions (ISRs), which recover with NSAIDs & do not worsen with subsequent treatments. Other than ISRs, no Gr 2 or higher adverse events have been observed to date. 11 pts remain on treatment, with the longest continuing therapy for 23 weeks. Ex-vivo analyses have shown dose-dependent pharmacodynamic effects.

Conclusions

At the dose levels evaluated to date, JK08 has been well tolerated, demonstrating preliminary disease stability & anticipated modulation of target immune cell populations in aggressive heavily pre-treated solid tumors. These results provide an initial characterization of JK08 biology & activity.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Salubris Biotherapeutics, Inc.

Funding

Salubris Biotherapeutics, Inc.

Disclosure

J. Johnson, J.P. McNally, A. McEwen, S. Murphy, S. Singhal: Financial Interests, Institutional, Full or part-time Employment: Salubris Biotherapeutics, Inc. All other authors have declared no conflicts of interest.