Corbus Pharmaceuticals Holdings, Inc. (NASDAQ: CRBP) announced new data from its Phase 1 dose escalation study of CRB-701 (SYS6002), a next-generation antibody-drug conjugate (ADC) targeting Nectin-4, at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) in San Francisco. The study, conducted in the US and UK, enrolled patients with metastatic urothelial cancer (mUC) and other solid tumors associated with Nectin-4 expression.
The Phase 1 Western study (NCT06265727) is a three-part trial evaluating the safety, pharmacokinetics, and efficacy of CRB-701. The dose escalation phase (Part A) included four dose cohorts (1.8 mg/kg, 2.7 mg/kg, 3.6 mg/kg, and 4.5 mg/kg Q3W). The data presented at ASCO GU included 38 participants with a data cut-off of December 2024, with 26 being evaluable for efficacy.
Safety and Tolerability
CRB-701 demonstrated a favorable safety profile. No dose-limiting toxicities were encountered during the dose escalation phase. Treatment-emergent adverse events were mostly grade 1 or 2. Notably, the incidence of peripheral neuropathy was low, with a combined rate of 4% (n=3/75) across both the Western and China studies. Skin and subcutaneous disorders were observed in 24% (n=9/38) of patients in the Western study, compared to 8% (n=3/37) in the China study, resulting in a combined rate of 16% (12/75).
Implementation of a proactive ocular toxicity protocol in the Western study led to a lower incidence of ocular adverse events (38%) in the 2.7 mg/kg and 3.6 mg/kg dose cohorts compared to the China study (66%).
Pharmacokinetics and Efficacy
The pharmacokinetic (PK) profile in the Western study was comparable to that in the China study. CRB-701 showed a longer ADC half-life and lower free-MMAE exposure relative to enfortumab vedotin (EV).
Responses were observed in several tumor types, including head and neck squamous cell carcinoma (HNSCC) tumors. The dose optimization phase (Part B) of the Phase 1 Western study has commenced, randomizing participants with HNSCC, cervical, and mUC tumors to the 2.7 mg/kg and 3.6 mg/kg cohorts.
About CRB-701
CRB-701 (SYS6002) is a next-generation ADC targeting Nectin-4, utilizing a site-specific, cleavable linker and a homogenous drug antibody ratio of 2, with MMAE as the payload. Nectin-4 is a clinically validated, tumor-associated antigen in urothelial cancer.
