Innovent has initiated a phase 1 study (NCT06349408) of IBI3001, a bispecific ADC that targets B7-H3 and EGFR, in patients with solid tumors. Additionally, Innovent is conducting a phase 1 trial (NCT05774873) of IBI344, a bispecific antibody that also targets B7-H3 and EGFR.
Schematic overview of crosstalk between the EGFR signaling and the B7/CD28 family
Recent research has suggested that the overexpression of novel B7/CD28 family proteins, including B7-H3 may be linked to EGFR signaling and could potentially lead to resistance to EGFR-targeted treatments by promoting an immune-depressed environment within the tumor microenvironment.
IBI3001
According to the statement by Innovent, IBI3001 is a site-specifically glycan-conjugated ADC that consists of a topoisomerase I inhibitor with multiple anti-tumor mechanisms of action: (1) enhanced EGFR signaling blockade; (2) EGFR- and B7-H3-aided payload internalization and cytotoxicity; and (3) potent bystander killing effects of ADC. The optimized B7-H3 arm not only enhances the EGFR signaling blockade but also reduces EGFR on-target toxicities. The abstract tested several tumor models, including colorectal, breast, pancreatic, and lung cancer.
The IND application for IBI3001 still needs to be submitted in China. The disclosed phase 1 clinical study is planned in Australia to enroll 180 participants to evaluate the efficacy and safety of IBI3001. No preferred cancer was disclosed while the trial of the ADCC-enhanced B7-H3/EGFR BsAb IBI334 mainly focused on lung cancer, head and neck squamous cell carcinoma, and RAS-wildtype colorectal cancer. The phase 2 stage of the trial of the B7-H3 ADC IBI129 aimed to enroll small-cell lung cancer and prostate cancer.
B7-H3/EGFR
Several ADCs and antibodies targeting B7-H3 in cancer patients are in development. Until now, no other product has focused on targeting both B7-H3 and EGFR, except for Innovent.
| Innovent B7H3 Pipeline |
The trials of IBI129 and IBI334 began in both China and Australia, while the trial of IBI3001 in China requires the submission of an IND application, which is expected to happen soon.
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