The U.S. Food and Drug Administration has granted fast track designation to CRB-701, an investigational antibody-drug conjugate developed by Corbus Pharmaceuticals Holdings, Inc., for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who have progressed after receiving platinum-based chemotherapy and anti-PD(L)-1 therapy.
This designation represents the second fast track status awarded to CRB-701, following a previous designation for relapsed or refractory metastatic cervical cancer granted in December 2024. The fast track program is designed to expedite the development and review of treatments for serious diseases with unmet medical needs.
Promising Early Clinical Results
The fast track designation was supported by encouraging preliminary data from an ongoing phase 1/2 clinical trial evaluating CRB-701 in patients with solid tumors expressing Nectin-4. Early results presented at the 2025 ASCO Annual Meeting demonstrated notable efficacy signals in head and neck cancer patients.
Among 37 patients currently enrolled in the study, those with HNSCC who underwent response evaluations showed an emerging objective response rate of 57% and a disease control rate of 86%. The pharmacokinetic data revealed that ADC and monomethyl auristatin E exposure were consistent with those reported in previous first-in-human studies.
Novel Mechanism of Action
CRB-701 is a next-generation antibody-drug conjugate that specifically targets Nectin-4, a protein commonly found in certain cancers. The drug utilizes a cleavable linker and controlled drug-to-antibody ratio, designed to deliver chemotherapy directly to cancer cells while minimizing damage to healthy tissue.
Comprehensive Clinical Trial Design
The ongoing phase 1/2 study, which began in April 2024 and is expected to complete in January 2027, is being conducted across sites in both the United States and Europe. The trial is designed as a three-part study evaluating safety, pharmacokinetics, and efficacy of CRB-701.
Part A focuses on dose escalation, testing four dose levels of CRB-701 administered every three weeks: 1.8 mg/kg, 2.7 mg/kg, 3.6 mg/kg, and 4.5 mg/kg. The primary endpoint is determining safety and the maximum tolerated dose. Part B aims to identify the recommended phase 2 dose both as monotherapy and in combination with anti-PD-1 therapy. Part C expands testing across multiple cancer types using the established optimal dose.
The study expects to enroll approximately 348 patients with confirmed diagnoses of select advanced or metastatic solid tumors expressing Nectin-4 that have progressed after at least one prior therapy. Eligible patients must be at least 18 years old and have tumors known to express Nectin-4.
Patient Population and Exclusion Criteria
The trial includes nine tumor types, with HNSCC being the most common (9 patients), followed by pancreatic ductal adenocarcinoma (7 patients), lung cancer (5 patients), and ovarian cancer (5 patients). Patients with active or uncontrolled central nervous system metastases, significant cardiovascular conditions, preexisting grade 2 or greater neuropathy, and various other comorbidities are excluded from participation.
Clinical Context for Head and Neck Cancer
Head and neck cancer encompasses several malignancies affecting areas including the mouth, throat, voice box, nasal cavity, and related structures. Most cases are squamous cell carcinomas that begin in the thin, moist lining of these regions. While tobacco-related head and neck cancers are declining in the United States, HPV-related cases are increasing, particularly in patients under age 50. Globally, head and neck cancers represent approximately 4.5% of all cancer diagnoses.
Treatment typically focuses on controlling the cancer while preserving essential functions such as speech, swallowing, and facial movement. Early detection and treatment significantly improve cure rates, making effective therapies for advanced disease particularly important.
Future Data Presentations
Additional trial data, including dose optimization findings, will be presented at the European Society for Medical Oncology (ESMO) Congress in October 2025. These results will provide further insight into CRB-701's safety profile and therapeutic potential for patients with difficult-to-treat head and neck cancers.
