SYS6002 (CRB-701) Shows Promising Safety and Efficacy in Nectin-4 Positive Tumors at ASCO 2024

Corbus Pharmaceuticals Holdings, Inc. (NASDAQ: CRBP) has recently announced significant progress in the clinical trial of SYS6002 (CRB-701), a next-generation antibody drug conjugate (ADC) targeting Nectin-4. This advancement was shared at the American Society of Clinical Oncology (ASCO) Annual Conference by Dr. Jian Zhang from Fudan University Shanghai Cancer Center. The Phase 1 trial, sponsored by CSPC Pharmaceuticals Group Limited in China, is assessing the safety and efficacy of SYS6002 in patients with advanced solid tumors who have not responded to standard treatments.

As of April 2024, 37 patients have been enrolled in the study, and 25 were evaluated for efficacy. SYS6002 demonstrated promising results, with a 44% overall response rate (ORR) and a 78% disease control rate (DCR) in metastatic urothelial cancer (mUC). In cervical cancer, the drug showed a 43% ORR and an 86% DCR at doses of 1.2 mg/Kg or higher. No dose-limiting toxicities have been observed up to the highest dose of 4.5 mg/Kg.

The clinical safety profile of SYS6002 is encouraging. Most adverse events (AEs) were mild to moderate, with no grade 4 or 5 AEs noted. Anemia and eye-related treatment emergent adverse events (TEAEs) were the most common. A grade 3 skin rash was reported but resolved without altering the dosing regimen. Similarly, two cases of milder skin rash were also resolved. A single case of grade 1 peripheral neuropathy associated with hypokalemia was reported, which resolved after treatment.

In terms of efficacy, early results are promising. The first confirmed stable disease was observed at 0.6 mg/Kg, while the first partial response was seen at 1.2 mg/Kg. The drug has shown a 40% ORR and a 73% DCR across all tumor types at doses of 2.7 mg/Kg or higher. There has been one additional partial response confirmed at 1.2 mg/Kg for an mUC patient.

Regarding pharmacology, the exposure of ADC and MMAE increased proportionally with the dose up to 2.7 mg/Kg. Beyond this dose, the levels of free MMAE started to level off. All dose levels have shown lower average levels of free MMAE compared to enfortumab vedotin, another ADC targeting Nectin-4.

Dr. Dominic Smethurst, Chief Medical Officer at Corbus, expressed satisfaction with the emerging safety data and the lower incidence of severe side effects. Dr. Yuval Cohen, Chief Executive Officer at Corbus, highlighted the potential for SYS6002 to be a differentiated Nectin-4 ADC. The corresponding U.S. clinical study is progressing well, with expected completion in Q4 2024 and data presentation in Q1 2025.

CRB-701 is designed to target Nectin-4, a clinically validated antigen in urothelial cancer, using a third-generation, site-specific cleavable linker and a homogenous drug antibody ratio. This design aims to reduce free MMAE concentrations in plasma, thereby minimizing associated toxicities. By administering SYS6002 on a three-week schedule, there is potential to improve clinical convenience and patient compliance.

Corbus Pharmaceuticals Holdings, Inc. is dedicated to precision oncology with a diversified portfolio aimed at defeating serious illnesses through innovative scientific approaches. Their pipeline includes CRB-701, CRB-601 (an anti-integrin monoclonal antibody), and CRB-913 (a CB1 inverse agonist for obesity treatment). The company is headquartered in Norwood, Massachusetts.