Corbus Pharmaceuticals announced positive data from its US and UK Phase 1 dose escalation study of CRB-701, a next-generation antibody-drug conjugate targeting Nectin-4. The study mirrored the highest doses of a previous China study and showed comparable safety, tolerability, and pharmacokinetic profiles, including low rates of peripheral neuropathy and skin toxicity. Clinical responses were observed in urothelial and cervical cancers, echoing the China study, and notably, responses were also seen in head and neck squamous cell carcinoma (HNSCC), a cancer type not previously studied with CRB-701.
These findings are potentially crucial for advancing the treatment of Nectin-4 expressing cancers. The confirmation of the safety and tolerability profile in a Western population strengthens the drug’s potential for broader application. The observed responses in HNSCC expand the possible indications for CRB-701 beyond urothelial and cervical cancers, suggesting a wider therapeutic scope than initially anticipated. This offers hope for patients with HNSCC, a cancer with significant unmet needs for effective therapies.
The Western study enrolled 38 participants, 26 of whom were evaluable for efficacy. The study used the same four dose cohorts (1.8, 2.7, 3.6, and 4.5 mg/kg) and Q3W regimen as the China study, which enrolled 37 participants with 25 evaluable for efficacy. No dose-limiting toxicities were observed in either study. Importantly, the Western study implemented a proactive ocular toxicity protocol, resulting in a lower incidence of related adverse events. CRB-701 demonstrated a longer half-life and lower free-MMAE exposure compared to enfortumab vedotin, a currently approved Nectin-4 targeting ADC. Efficacy data showed responses across several tumor types, including a confirmed response in cervical cancer and promising activity in HNSCC, with 4 partial responses observed among 7 evaluable participants. Interestingly, responses were observed even in patients with low Nectin-4 expression levels, consistent with preclinical data.
The dose optimization phase of the Western study is now underway, focusing on the 2.7 mg/kg and 3.6 mg/kg doses in HNSCC, cervical, and urothelial cancers. The positive data from both the China and Western studies, especially the safety profile and efficacy signals in multiple tumor types, support further clinical development of CRB-701. This progress positions CRB-701 as a potential competitor in the Nectin-4 targeting ADC space and may lead to a new treatment option for patients with these difficult-to-treat cancers. The expansion into HNSCC adds another dimension to the drug’s potential and warrants further investigation.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
