IND Required for ITC-6146RO for Solid Tumors Overexpressing the B7-H3 Protein

On August 29, 2025, a clinical trial plan (Investigational New Drug application) was submitted to the Ministry of Food and Drug Safety (MFDS) of South Korea to initiate phase 1 clinical trials for ITC-6146RO.

ITC-6146RO is an antibody-drug conjugate (ADC) designed to target solid tumors overexpressing the B7-H3 protein, such as metastatic castration-resistant prostate cancer (mCRPC), non-small cell lung cancer (NSCLC), and triple-negative breast cancer (TNBC).

This candidate delivers a cytotoxic payload to cancer cells while minimizing damage to healthy tissue, utilizing advanced linker and payload technologies to enhance its therapeutic potential. The ADC targets B7-H3, a transmembrane glycoprotein encoded by the CD276 gene, which is highly expressed in various cancers but has limited presence in normal tissues, making it an effective target for cancer therapies. ITC-6146RO employs an Ortho Hydroxy-Protected Aryl Sulfate (OHPAS) linker, which ensures high biostability and can be activated by enzymes, light, or pH changes for precise payload release. Additionally, Payload Modification Technology (PMT) reduces non-specific uptake by normal cells, decreasing off-target effects and improving the therapeutic index.

Preclinical studies have demonstrated ITC-6146RO’s potent antitumor effects in B7-H3-positive murine xenograft and patient-derived xenograft models. It exhibits long-lasting efficacy and high stability in mouse and IgG-depleted human plasma, with a strong safety profile. While the specific payload is not fully detailed, it may resemble that of ITC-6102RO, another B7-H3-targeted ADC using a soluble derivative of pyrrolobenzodiazepine, a DNA cross-linking agent. ITC-6146RO is the lead candidate in its B7-H3 program, indicating it may be an optimized iteration. The planned trial will evaluate safety, tolerability, pharmacokinetic characteristics, and initial antitumor effects in patients with progressive or metastatic cancer who have failed standard treatments, pending MFDS approval.

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