FDA Grants Fast Track Designation to CRB-701 in Pretreated Recurrent HNSCC

The next-generation ADC, CRB-701, demonstrated an emerging objective response rate of 57% in a subgroup of patients with HNSCC.

The FDA has granted fast track designation (FTD) to CRB-701, a next-generation antibody drug conjugate targeting nectin-4, as therapy for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) previously treated with platinum-based chemotherapy and an anti-PD(L)1 therapy, according to a press release from the developer, Corbus Pharmaceuticals.¹

Of the patients with HNSCC enrolled in an ongoing, open-label phase 1/2 trial (NCT06265727), stable disease was observed in 2 patients, and partial responses were observed in 4 patients. The emerging objective response rate was 57% (n = 4/7 patients), and the emerging disease control rate was 86% (N = 6/7 patients); the lone patient did not exhibit disease control and had clinical progression without scans.²

Results from the dose-escalation portion of the trial, which evaluated the safety, efficacy, and pharmacokinetics of CRB-701 in patients with nectin-4 expressing advanced solid tumors, were presented at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium. Additional data from the dose-optimization portion of the trial will be shared at the 2025 European Society of Medical Oncology Congress.

Previously, in December 2024, CRB-701 was granted FTD by the FDA for relapsed/refractory metastatic cervical cancer.³

“Preliminary efficacy was observed at multiple doses in patients exhibiting a wide range of nectin-5 [immunohistochemistry]-derived H-scores, and, for the first time, we report efficacy in patients with HNSCC and the first unconfirmed complete response in a patient with cervical carcinoma,” wrote lead study Cesar A. Perez, MD, the director of the drug development unit at the Sarah Cannon Research Institute at Florida Cancer Specialists and Research Institute, and coauthors, in the poster.² “These results support the continued development of CRB-701 in patients with solid tumors expressing nectin-4. Part B of the CRB-701 study is continuing with dose optimization cohorts in HNSCC, cervical cancer, and bladder cancer.”

Across all dose groups, the trial enrolled 38 patients with varying types of primary tumors, including HNSCC (n = 9), pancreatic ductal adenocarcinoma (n = 7), lung cancer (n = 5), and ovarian cancer (n = 5), among others.

The median age of patients was 62 years, 57.9% were female, and 71.1% had an ECOG performance status of 1; the median number of previous therapies was 3 (range, 1-8), 68.4% of patients had a creatinine clearance greater than 60 mL per minute, and 60.5% had a glycated hemoglobin level less than 6.5%.

Treatment was designed such that after the first dose, a group of patients was enrolled, and subsequent cohorts received increasing doses of CRB-701 until the maximum tolerated dose was reached.

The first group received 1.8 mg/kg of CRB-701 every 3 weeks, the second group received 2.7 mg/kg every 3 weeks, the third group received 3.6 mg/kg every 3 weeks, and the fourth group received 4.5 mg/kg every 3 weeks. Treatment was continued until intolerable toxicity, death, withdrawal of consent, or progressive disease.

The primary end point of the dose escalation portion of the trial was the occurrence of dose-limiting toxicities. Secondary end points included the incidence of treatment-emergent adverse events (TEAEs), tumor assessments, and pharmacokinetics.

Across all doses and tumor types, 15.8% of patients discontinued treatment, 5.3% had a dose reduction, and 44.7% had a dose interruption. Sorted by dose levels, these numbers were as follows: at the 1.8 mg/kg dose level (n = 13), 15.4% (n = 2) discontinued treatment, 0 had a dose reduction, and 53.8% (n = 7) had a dose interruption; at the 2.7 mg/kg dose level (n = 11), 0% discontinued treatment, 9.1% (n = 1) had a dose reduction, and 36.4% (n = 4) had a dose interruption; at the 3.6 mg/kg dose level (n = 10), 20.0% (n = 2) discontinued treatment, 10.0% (n = 1) had a dose reduction, and 40.0% (n =4) had a dose interruption; and at the 4.5 mg/kg dose level (n = 4), 50.0% (n = 2) discontinued treatment, 0% had a dose reduction, and 50.0% (n = 2) had a dose interruption.

Treatment-related treatment-emergent adverse events (TEAEs) that occurred in more than 15% of patients were dysgeusia, fatigue, alopecia, and dry eye. Rash occurred in 10.5% of patients, maculopapular rash in 5.3%, and peripheral sensory neuropathy in 5.3%. Further, 47.4% of patients reported experiencing an eye disorder, with 1 instance of grade 3 keratitis and watery eye each.

Serious TEAEs occurred in 23.7% of patients, with photophobia being the only serious TEAE related to treatment. AEs led to treatment discontinuation in 13.2% of patients. Just below 50% of dose interruptions (n = 8/17) occurred due to eye disorders.

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 17, 2025. https://tinyurl.com/wzyb6fuu
2. Perez CA, Gandhi N, 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.807
3. FDA grants fast track designation to CRB-701 for the treatment of relapsed or refractory metastatic cervical cancer. News release. Corbus Pharmaceuticals. December 3, 2024. Accessed September 17, 2025. https://tinyurl.com/mubwyb7u