FDA Grants Fast Track Designation to CRB-701 for Pretreated Recurrent or Metastatic HNSCC

The FDA has granted fast track designation to CRB-701 (SYS6002), a next-generation antibody-drug conjugate (ADC) that targets Nectin-4, for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who previously received platinum-based chemotherapy and an anti–PD-L1 therapy.1

The fast track designation for CRB-701 in patients with recurrent or metastatic HNSCC was supported by data from the ongoing phase 1/2 study (NCT06265727), evaluating the safety and efficacy of CRB-701 for the treatment of solid tumors that have high expression of nectin-4.

The data from the study will be presented at the 2025 ESMO Congress.

What Are the Preliminary Efficacy and Pharmacokinetic Data?

Early data, presented at the 2025 ASCO Annual Meeting, revealed that among the 37 patients currently on the study, an emerging ORR of 57% and an emerging disease control rate of 86% were observed in patients with HNSCC who underwent response evaluations.2 Notably, ADC and monomethyl auristatin E exposure were consistent with those reported in a previous first-in-human study.

What Is the Background and Design of the Phase 1/2 Study?

In December 2024, CRB-701 was granted fast track designation for the treatment of relapsed/refractory metastatic cervical cancer. The ongoing phase 1/2 study, conducted in both the US and Europe, began in April 2024 and is expected to be completed in January 2027.3 Of note, the study is expected to enroll approximately 348 patients with a confirmed diagnosis of select advanced or metastatic solid tumors that express Nectin-4 and have progressed after at least 1 prior therapy or in those who have no other standard therapy with proven clinical benefit. Patients on the study must be at least 18 years of age.

Moreover, patients with active or uncontrolled central nervous system metastases are not permitted on the study. A history of solid tumors other than the diseases allowed on the study, a history of and/or current cardiovascular events and or other conditions occurring within the previous 6 months, and preexisting grade 2 or greater neuropathy were not allowed on the study. Additionally, patients who have hemoglobin A1C levels of at least 8%, have uncontrolled diabetes mellitus, known diabetic neuropathy, and/or active ocular disease at baseline were also not permitted, as well as those with chronic severe liver disease or liver cirrhosis, interstitial lung disease or pneumonitis within 6 months of starting treatment, and other significant comorbidities.

Furthermore, the trial is a 3-part study, including 4 doses of CRB-701 in part A: CRB-701 every 3 weeks at a dose level of 1.8 mg/kg, 2.7 mg/kg, 3.6 mg/kg, and 4.5 mg/kg.2,3 Part B of the study includes high and low doses of CRB-701, and part C initiates the expansion portion of the trial. Specifically, in part C of the study, patients in cohorts 1, 3, 5, and 7 receive the recommended phase 2 dose (RP2D) of CRB-701 as an intravenous infusion over 30 minutes, followed by infusion with an anti–PD-1 therapy. In cohorts 2, 4, and 6 of part C, patients are treated with the RP2D of CRB-701 alone.

The primary end point in part A of the study is to determine safety, including the maximum tolerated dose of CRB-701; the primary end point of parts B and C is the objective response rate (ORR) per RECIST 1.1 criteria.3 Secondary end points include safety in all parts of the study and pharmacokinetics.

Additionally, 9 tumor types were included on the study, most commonly including HNSCC (n = 9), pancreatic ductal adenocarcinoma (n = 7), lung cancer (n = 5), and ovarian cancer (n = 5).2

References

1. FDA grants fast track designation to Corbus Pharmaceuticals’ nectin-4 targeting ADC CRB-701 in head and neck squamous cell carcinoma. News release. Corbus Pharmaceuticals. September 16, 2025. Accessed September 16, 2025. https://ir.corbuspharma.com/news-events/press-releases/detail/448/fda-grants-fast-track-designation-to-corbus-pharmaceuticals-nectin-4-targeting-adc-crb-701-in-head-and-neck-squamous-cell-carcinoma
2. A phase 1/2 study to investigate CRB-701 in solid tumors. ClinicalTrials.gov. Updated June 3, 2025. Accessed September 16, 2025. https://www.clinicaltrials.gov/study/NCT06265727
3. Perez CA, Gandhi NJ, Mosalpuria K, et al. Phase I dose-escalation study of the next-generation nectin-4 targeting antibody–drug conjugate CRB-701 (SYS6002) in US and UK patients with urothelial cancer and other solid tumors. J Clin Oncol. 2025;43(suppl 5):807. doi:10.1200/JCO.2025.43.5_suppl.80