Novel ADC Earns FDA Fast Track in Head and Neck Cancer

The FDA has granted fast track designation to the antibody-drug conjugate (ADC) CRB-701 for the treatment of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) previously treated with platinum-based chemotherapy and an anti–PD-(L)1 agent.¹

The FDA’s fast track is a program intended to facilitate the development and expedite the review of agents that fill serious unmet medical needs.² With this designation, Corbus Pharmaceuticals, the sponsor, may be eligible for more frequent meetings with the FDA, accelerated approval, priority review, and rolling review.

CRB-701 is a next-generation ADC targeting Nectin-4.¹ A fast track designation was given to the same agent for the treatment of relapsed or refractory metastatic cervical cancer in December 2024.³

An ongoing phase 1/2 study is evaluating CRB-701 in patients with solid tumors associated with high Nectin-4 expression.¹ Updated data from the dose-optimization portion of the study will be presented at the 2025 European Society for Medical Oncology (ESMO) Annual Congress on October 19, 2025.

Data from the phase 1 portion were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.^4,5Here, CRB-701 showed promising antitumor responses across multiple dose levels and was generally well tolerated.

At a data cutoff of May 2024, responses were observed across tumor types. Specifically, at dose levels of 2.7 mg/kg or higher, the overall response rate (ORR) was 40%. This included 6 partial responses (PRs) and 2 unconfirmed responses.The disease control rate (DCR) was 73%.

In patients with metastatic urothelial cancer (n = 9), the ORR was 44% and included 4 PRs and 1 unconfirmed response. The DCR was 78%. Patients with cervical cancer (n = 7) had an ORR of 43%, including 3 PRs and 1 unconfirmed response, and the DCR was 86%.

As of the data cutoff, CRB-701 demonstrated its first confirmed case of stable disease at the 0.6 mg/kg dose level and the first confirmed PR in the metastatic urothelial cancer cohort at the 1.2 mg/kg dose level. Early pharmacokinetic analysis revealed consistently lower levels of free monomethyl auristatin E across all dose levels compared with enfortumab vedotin (Padcev).

In terms of safety, the dose-escalation phase primarily involved grade 1/2 adverse events (AEs), with no grade 4/5 AEs or dose-limiting toxicities reported to date. The most common treatment-emergent AEs were anemia and eye-related events. One patient treated with the 2.7 mg/kg dose had a grade 3 rash lasting 8 days, which did not require dose modification or interruption. Further, there were 2 cases of skin rash (grade 1 and grade 2) resolved without intervention.

One case of grade 1 peripheral neuropathy occurred alongside grade 3 hypokalemia, both resolving within 10 days after potassium replacement therapy. There were 2 grade 3 corneal disorders seen at the 2.7 mg/kg and 3.6 mg/kg dose levels, leading to the implementation of preventive eye care measures. No corneal events have been noted at the 4.5 mg/kg dose level. Over 50% of patients presented with corneal disorders or dry eye symptoms at baseline.

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/5n7ak5pk

2. Fast Track. US FDA. Updated August 13, 2024. Accessed September 17, 2025. https://tinyurl.com/y748ywj9

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/3r38fyyc

4. Ye DW, Zhang J, Yang H, et al. Clinical update on the first-in-human trial of SYS6002 (CRB-701), a next-generation, Nectin-4 targeting, MMAE bearing, antibody drug conjugate. J Clin Onc. 2024;42(suppl 16):3151. doi:10.1200/JCO.2024.42.16_suppl.3151

5. SYS6002 (CRB-701) a next-generation Nectin-4 targeting antibody drug conjugate continues to demonstrate encouraging safety and efficacy observed in patients with Nectin-4 positive tumors in a clinical update presented at ASCO 2024. News release. Corbus Pharmaceuticals. June 1, 2024. Accessed September 17, 2025. https://tinyurl.com/38zppxxs