FDA Agrees to Trial Designs for CRB-701 in HNSCC and Cervical Cancer

The FDA and Corbus Pharmaceuticals Holdings, Inc., have agreed on second-line registrational study designs evaluating CRB-701, a next-generation antibody drug conjugate (ADC) targeting Nectin-4, in head and neck squamous cell carcinoma (HNSCC) and cervical cancer, according to a news release from the manufacturer.¹

Trial Design

The study for HNSCC is a single arm, randomized controlled study exploring the efficacy and safety of CRB-701 compared with physicians’ choice chemotherapy with potential accelerated approval using objective response rate (ORR) as the primary end point and potential full approval granted on overall survival (OS) benefit.

The cervical cancer trial is a single arm, randomized controlled study exploring the efficacy and safety of CRB-701 compared with physicians’ choice of chemotherapy or tisotumab vedotin-tftv (Tivdak) with potential accelerated approval using ORR as the primary end point and potential full approval granted on OS benefit.

Continued interactions with the FDA is planned to finalize the protocols and statistical analysis plans for the registrational studies.

Updated clinical data from the Phase 1/2 study (NCT06265727) of CRB-701 in both HNSCC and cervical cancer will be presented at the upcoming 2026 American Society of Clinical Oncology (ASCO) Annual Meeting to be held May 29 – June 2 in Chicago. Data will include clinical response durability as well as patient subgroup analysis.

Corbus previously presented dose optimization data from the study,² including encouraging efficacy and safety findings, at the 2025 European Society for Medical Oncology Congress. Part A (escalation) enrolled adults with locally advanced/metastatic solid tumours. Nectin-4 positivity was evaluated using retrospective H-scores. A Bayesian Optimal Interval design was used with 4 dose groups (1.8, 2.7, 3.6 and 4.5 mg/kg; each every 3 weeks). A time-to-event Bayesian optimal phase 2 design was used for part B (optimization). Adults with metastatic urothelial cancer (mUC), cervical cancer or head and neck squamous cell carcinoma (HNSCC) who had received 1 or more lines of therapy were randomly assigned 1:1 to 2.7 mg/kg or 3.6 mg/kg CRB-701 every 3 weeks. Safety, tolerability and antitumour activity were assessed.

As of April 2025, 54 patients with primary tumors of 10 different types had completed part A, and 16 patients with HNSCC, mUC or cervical cancer had enrolled in part B. Responses were observed at multiple doses in mUC and non-urothelial tumours, notably HNSCC, cervical and endometrial. Efficacy data and Nectin-4 H-scores will be presented at the congress. No dose-limiting toxicities occurred in part A.

Safety

Most adverse events (AEs) were grade 1 or 2. Grade ≥3 AEs were reported in ∼30.0% of patients. AEs reported in 15% or more of patients were alopecia, dysgeusia, fatigue, keratitis, blurred vision and dry eye. Rates of skin rash, neutropenia, fatigue and peripheral neuropathy were considerably lower than those observed with other monomethyl auristatin E ADCs.

The company also anticipates reporting data with CRB-701 in combination with pembrolizumab (Keytruda) in first-line HNSCC patients in Q4 2026 to support potential further registration-enabling trials.

“We’re pleased to share this important regulatory update as we continue to progress CRB-701 as a novel oncology therapeutic to address unmet medical needs for patients. We look forward to sharing updated monotherapy data on CRB-701 at ASCO and expect to initiate a registrational study for CRB-701 in second-line HNSCC in mid-2026,” said Yuval Cohen, PhD, chief executive officer of Corbus.

Dr Cohen continued, “This milestone marks an important transition from clinical proof of concept to pending late-stage registrational development and the potential for regulatory submission of CRB-701.”

REFERENCE

1. Corbus Pharmaceuticals Announces Broad Alignment with FDA on Registration Path for CRB-701 in Second-Line HNSCC and Cervical Cancer. News release. April 7, 2026. Accessed April 7, 2026. https://tinyurl.com/3w4bkzr7

2. Perez CA, Mantia C, Cohn A, et al. Phase I/II study of the next-generation Nectin-4-targeting antibody–drug conjugate CRB-701 (SYS6002) in patients with urothelial and non-urothelial solid tumours. Ann Oncol. 2025;36(suppl 2):S593-594. doi:10.1016/j.annonc.2025.08.1536