Phase I/II study of next-generation Nectin-4–targeting ADC CRB-701 (SYS6002) in recurrent or metastatic cervical cancer
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Next-Gen Nectin-4 ADC CRB-701 Shows Early Promise in Recurrent/Metastatic Cervical Cancer
CRB-701 is a next-generation ADC targeting Nectin-4, a protein frequently overexpressed in cervical cancer and other solid tumors, developed under an exclusive license agreement signed in February 2023 between Corbus Pharmaceuticals and CSPC Megalith Biopharmaceutical (a subsidiary of CSPC Pharmaceutical Group). It represents an important advance in the evolving treatment landscape beyond conventional surgery, radiation, and chemotherapy, addressing a high unmet need in relapsed or refractory disease.
The program is currently being evaluated in an ongoing Phase I/II trial in the United States and Europe, along with a Phase III study in China. It received US FDA Fast Track designation in December 2024 for relapsed or refractory metastatic cervical cancer.
In April 2026, The FDA and Corbus Pharmaceuticals agreed on second-line registrational study designs evaluating CRB-701 in head and neck squamous cell carcinoma (HNSCC) and cervical cancer.
Updated Phase I/II data in cervical cancer were presented at the 2026 ASCO Annual Meeting, demonstrated compelling clinical activity as follows:
|
Phase I/II trial Data | ||||
|
Category |
Parameter |
2.7 mg/kg (n=38) |
3.6 mg/kg (n=34) | |
|
Efficacy |
cORR (90% CI) |
18.4% (9.0–31.8) |
34.4% (20.6–50.4) | |
|
Median DoR (95% CI) |
6.8 months (4.4–NE) |
8.0 months (4.2–NE) | ||
|
Median PFS (95% CI) |
2.8 months (1.4–5.7) |
4.3 months (2.9–9.5) | ||
|
Safety |
Treatment-related keratitis, all grades n (%) |
39.5% |
79.4% |
58.3% |
|
Grade 1 keratitis |
13.2% |
8.8% |
11.1% | |
|
Grade 2 keratitis |
21.1% |
61.8% |
40.3% | |
|
Grade 3 keratitis |
5.3% |
8.8% |
6.9% | |
|
Median duration of exposure (days) |
64.0 (23.0–178.0) |
106.5 (23.0–189.0) |
83.5 (23.0–185.0) | |
|
Median relative dose intensity (%) |
97.7 (85.7–100.0) |
86.2 (70.2–98.8) |
96.1 (79.7–100.0) | |
|
Dose interruption % |
39.5% |
61.8% |
50.0% | |
|
Dose reduction (%) |
10.5% |
26.5% |
18.1% | |
|
Treatment discontinuation (%) |
0 |
8.8% |
4.2% | |
|
cORR: Confirmed Overall Response Rate; DoR: Duration of Response; PFS: Progression-Free Survival; NE: Not Evaluated | ||||
KOL insights:
“CRB-701’s stable linker–payload design with site-specific conjugation reduces free MMAE exposure and extends half-life versus enfortumab vedotin, while demonstrating activity regardless of Nectin-4, HPV, or PD-(L)1 status, reinforcing its therapeutic potential in cervical cancer.”– Expert Opinion
“CRB-701 could represent a promising therapeutic option for recurrent/metastatic cervical cancer, addressing a setting where current treatments are limited by modest efficacy and durability, particularly after immunotherapy failure. Nectin-4 ADC data show encouraging anti-tumor activity without biomarker selection, including ~37% ORR and complete responses in heavily pretreated patients, supporting its clinical potential.”– Expert Opinion
Conclusion:
Cervical cancer originates in the epithelial cells of the cervix, the lower part of the uterus connecting the uterine cavity to the vagina. In 2025, cervical cancer accounted for approximately 13,459 incident cases in the United States. The treatment landscape has progressively evolved with the introduction of targeted and immune-based therapies. Bevacizumab (AVASTIN), approved in 2014, remains a key anti-angiogenic backbone in advanced cervical cancer, alongside multiple biosimilars. Immunotherapy has further reshaped the field, with pembrolizumab (KEYTRUDA) establishing checkpoint inhibition as a treatment option. ADC innovation is also emerging, with tisotumab vedotin (TIVDAK) being the first approved ADC in cervical cancer, despite ocular toxicity limitations.
In this evolving landscape, CRB-701, a next-generation Nectin-4–targeting ADC, has demonstrated encouraging early clinical activity in recurrent/metastatic cervical cancer, with dose-dependent improvements in response and a manageable safety profile in Phase I/II evaluation. Overall, these findings indicate its potential to broaden treatment options and enhance the competitive landscape in Nectin-4–positive cervical cancer.
Executive Summary
Corbus Pharmaceuticals’ CRB-701 is a next-generation Nectin-4–targeting antibody-drug conjugate (ADC) designed to selectively deliver a potent cytotoxic payload to tumor cells in cervical cancer and other Nectin-4–expressing solid tumors. In the Phase I/II study of patients with recurrent or metastatic cervical cancer, CRB-701 demonstrated encouraging clinical activity, with a confirmed overall response rate of 34.4% at the 3.6 mg/kg dose, along with improved progression-free survival and duration of response versus the lower dose cohort, indicating dose-dependent efficacy benefit. These findings support CRB-701 as a promising next-generation ADC with potential to expand treatment options in Nectin-4–positive cervical cancer and other solid tumors.