A phase 1/2 study of the next-generation nectin-4–targeting antibody-drug conjugate CRB-701 (SYS6002) in patients with recurrent or metastatic cervical cancer.

Abstract

5508 Background: CRB-701 is a next-generation Nectin-4–targeted monomethyl auristatin E (MMAE)-based antibody–drug conjugate with differentiated safety, efficacy and pharmacokinetics compared with other agents in the same class. As previously reported, CRB-701 demonstrated antitumor responses independent of Nectin-4 expression levels in solid tumors, notably in patients with heavily pretreated head and neck squamous cell carcinoma (HNSCC) and cervical cancer, as well as those with urothelial carcinoma. Here, we provide data from this phase 1/2 trial in patients with cervical cancer enrolled in dose escalation (part A) and dose optimization (part B) (NCT06265727). Methods: Patients with recurrent or metastatic (R/M) cervical cancer who had received ≥ 1 line of therapy were enrolled. Part A employed a Bayesian Optimal Interval design with four doses (1.8, 2.7, 3.6 and 4.5 mg/kg; each every 3 weeks [Q3W]) to determine the maximum tolerated dose. In part B, the pharmacologically active dose range identified in part A was evaluated using a time-to-event Bayesian optimal phase 2 design. Patients were randomized 1:1 to receive CRB-701 at 2.7 or 3.6 mg/kg Q3W. The primary endpoints for parts A and B were dose-limiting toxicities and objective response rate (ORR), respectively. Safety, tolerability and pharmacokinetics were also assessed. Nectin-4 expression was evaluated retrospectively. Results: As of September 2025, 54 patients with cervical cancer had enrolled across parts A and B. At the time of data cut, most patients were awaiting a confirmatory scan. The unconfirmed ORR was 22.2% (4/18 evaluable patients) at the 2.7 mg/kg dose and 37.5% (6/16 evaluable patients) at the 3.6 mg/kg dose. Confirmed partial responses were observed in 1/18 participants at the 2.7 mg/kg dose and 3/16 patients at the 3.6 mg/kg dose. One patient had a confirmed complete response at the 2.7 mg/kg dose. The safety profile of CRB-701 was broadly consistent with earlier findings: keratitis, anemia, alopecia, fatigue and dysgeusia were the most frequently reported treatment-emergent adverse events (≥ 15% of overall solid tumor population [N = 167]). An expanded efficacy analysis reporting an additional 6 months of follow-up, including ORR, duration of response and progression-free survival, will be presented at the congress. Subgroup analyses by treatment history and disease extent will also be presented. Conclusions: CRB-701 has shown promising efficacy in patients with R/M cervical cancer, as well as a favorable safety profile compared with other MMAE-based therapies. Ongoing evaluation of CRB-701 will determine its potential as a new treatment option for this patient population. Clinical trial information: NCT06265727 .