ibentatug (ZB131)

P1/2, N=35, Completed, ZielBio, Inc. | Active, not recruiting --> Completed | Trial completion date: Mar 2024 --> Sep 2023 | Trial primary completion date: Jan 2024 --> Aug 2023

Interim data from dose-escalation of this first-in-class, anti CSP antibody, demonstrates good tolerability with encouraging signs of activity and target engagement in heavily pretreated pts. Results support further clinical evaluation of ZB131 in dose-expansion cohorts including OC and including combination therapy with gemcitabine. Clinical trial information: NCT 05074472.

Previous data from our group and others suggesting that CSP plays a role in chemoresistance led us to evaluate the efficacy of ZB131 in combination with gemcitabine. In summary, ZB131 is an exciting new avenue for the treatment of CCA and other CSP-positive cancers with an excellent safety profile and strong antitumor activity in vitro and in murine models. Phase I clinical trials of ZB131 have been initiated.

Similar in-vivo and in-vitro techniques were used to characterize ZB131’s effect in combination with cisplatin. ZB131 demonstrates high affinity (0.4±0.1nM) and specificity for both murine and human CSP. CSP is a novel highly abundant therapeutic target exclusively localized to the cell surface of ovarian, colorectal, lung, and pancreatic cancers which collectively account for more than half of all estimated cancer deaths. Our findings illustrate that CSP-targeting with ZB131 induces cytotoxicity by activating stress pathways and dampening proliferation and survival pathways. This study serves as the basis for informing a novel treatment strategy for CSP-positive tumors.