9MW2821 granted breakthrough therapy designation in China for urothelial carcinoma

China's National Medical Products Administration (NMPA) has granted a breakthrough therapy designation to the investigational nectin-4 targeting antibody drug conjugate (ADC) 9MW2821 for the potential treatment of patients with locally advanced or metastatic urothelial carcinoma that progressed after previous platinum-based chemotherapy and PD-(L)1 inhibitor therapy.¹

9MW2821 is currently being assessed vs chemotherapy in a phase 3 trial in patients with locally advanced or metastatic urothelial carcinoma.

Breakthrough therapy designation is granted to therapies that have demonstrated significant safety or efficacy advantages over currently approved options in early clinical trials. With this designation, the development process for 9MW2821 can benefit from prioritized engagement with China’s Center for Drug Evaluation as well as expedited review and approval.

In the US, the FDA has granted a fast track designation to 9MW2821 for advanced, recurrent, or metastatic esophageal squamous cell carcinoma, recurrent or metastatic cervical cancer that progressed on or following treatment with a platinum-based chemotherapy regimen, and locally advanced or metastatic nectin-4 positive triple negative breast cancer (TNBC). The FDA also granted an orphan drug designation to the ADC for the treatment of esophageal cancer.

Data on 9MW2821

Data from a phase 1/2 trial (NCT05216965) of 9MW2821 in patients with advanced solid tumors were recently presented at the 2024 American Society for Clinical Oncology Annual Meeting in Chicago, Illinois.^2.3

Among patients with urothelial carcinoma, the objective response rate was 62.2% (95% CI, 44.76%-77.54%) and the disease control rate was 91.9% (95% CI, 78.09%-98.30%). The median progression-free survival was 8.8 months (95% CI, 3.81-NR), and the median overall survival was 14.2 months.

Regarding safety, the therapy demonstrated adequate tolerability among all patients included in the trial.

In total, the phase 2 study included 240 patients with advanced solid tumors, 37 of whom had urothelial carcinoma. Other solid tumor types included in the analysis were cervical cancer, esophageal cancer, and TNBC. All patients were treated with 9MW2821 at the recommended phase 2 dose level of 1.25 mg/kg.

In addition to the study of 9MW2821 in patients with advanced solid tumors, the ADC is also being assessed vs chemotherapy in a phase 3 trial (NCT06196736) in patients with locally advanced or metastatic urothelial carcinoma who have previously received platinum-based chemotherapy and PD-(L)1 inhibitor therapy.⁴

In total, the trial plans to enroll 420 patients who will receive either 9MW2821 dosed intravenously at 1.25 mg/kg on days 1, 8, and 15 of every 28-day cycle or to intravenous infusion of 75 mg/m² docetaxel or 175 mg/m² paclitaxel on day 1 of every 21-day cycle. The dual primary end points for the study are progression-free survival and overall survival. Secondary outcome measures include objective response rate, duration of response, disease control rate, and safety.

Primary completion of the study is expected in December 2026.

References

1. Mabwell's novel nectin-4 targeting ADC 9MW2821 granted Breakthrough Therapy Designation by China's NMPA. News release. Mabwell. Published online and accessed August 12, 2024. https://www.prnewswire.com/news-releases/mabwells-novel-nectin-4-targeting-adc-9mw2821-granted-breakthrough-therapy-designation-by-chinas-nmpa-302219866.html

2. Zhang J, Liu R, Gao S, et al. 9MW2821, a nectin-4 antibody-drug conjugate (ADC), in patients with advanced solid tumor: Results from a phase 1/2a study. J Clin Oncol. 2024;42(suppl 16):3013. doi:10.1200/JCO.2024.42.16_suppl.3013

3. Mabwell announces 9MW2821 clinical data and latest progress to be presented at 2024 ASCO Annual Meeting. News release. Mabwell. May 24, 2024. Accessed August 12, 2024. https://www.prnewswire.com/news-releases/mabwell-announces-9mw2821-clinical-data-and-latest-progress-to-be-presented-at-2024-asco-annual-meeting-302155031.html

4. A study to evaluate 9MW2821 versus chemotherapy in subjects with previously treated locally advanced or metastatic urothelial cancer. ClinicalTrials.gov. Last updated January 9, 2024. Accessed August 12, 2024. https://clinicaltrials.gov/study/NCT06196736