Corbus Pharmaceuticals (Nasdaq: CRBP) announced that the FDA has aligned with its proposed registrational study designs for CRB-701, a Nectin-4–targeting antibody-drug conjugate (ADC), in second-line head and neck squamous cell carcinoma and cervical cancer, clearing the path toward randomized trials with objective response rate as the primary endpoint for potential accelerated approval.
The ongoing Phase I/II study (NCT06265727) is a recruiting, open-label trial enrolling patients with Nectin-4–expressing advanced solid tumors. No patient numbers, dosing, or efficacy data are disclosed in this announcement; updated monotherapy results are scheduled for presentation at the 2026 ASCO Annual Meeting, May 29–June 2 in Chicago.
The agreed registrational designs call for two separate randomized controlled studies. In second-line HNSCC, CRB-701 will be compared with physician's choice chemotherapy, with ORR as the primary endpoint for accelerated approval and overall survival anchoring potential full approval. In cervical cancer, the comparator arm broadens to include physician's choice chemotherapy or Tivdak (tisotumab vedotin), under the same dual-endpoint framework. Corbus said it expects to initiate the HNSCC registrational study in mid-2026; protocols and statistical analysis plans for both studies remain under finalization with the FDA. No efficacy numbers from the Phase I/II program were released alongside this regulatory update.
About CRB-701
CRB-701 is an ADC licensed from China-based CSPC Megalith Biopharmaceutical in 2023 that pairs a Nectin-4–directed antibody with a site-specific, cleavable linker and a homogeneous drug-to-antibody ratio of 2, using monomethyl auristatin E as the cytotoxic payload. The low DAR and site-specific conjugation are designed to reduce free MMAE systemic exposure relative to enfortumab vedotin (Padcev), the approved Nectin-4 ADC whose indication is currently limited to urothelial carcinoma. Whether that structural distinction translates into a differentiated clinical safety profile in HNSCC or cervical cancer remains to be established in the registrational program. The FDA has granted CRB-701 Fast Track designation in both indications.
In the second-line HNSCC setting, the approved landscape consists primarily of anti-PD-1 agents — pembrolizumab and nivolumab — along with cetuximab and cytotoxic chemotherapy. With checkpoint inhibitors now embedded in first-line regimens, a growing proportion of patients entering second-line treatment have already progressed on immunotherapy, a population for which no approved targeted option exists. Nectin-4 expression is independent of PD-L1 status, which is the mechanistic basis for CRB-701's potential activity in this post-IO population, though that hypothesis requires prospective validation.