9MW2821/toripalimab awarded breakthrough therapy designation in China for mUC

China’s National Medical Products Administration (NMPA) has granted a breakthrough therapy designation (BTD) to the investigational Nectin-4 targeted antibody drug conjugate (ADC) 9MW2821 in combination with toripalimab-tpzi (Loqtorzi) for treatment-naïve, unresectable, locally advanced or metastatic urothelial carcinoma (la/mUC), Mabwell reported in a news release.¹

A pivotal phase 3 trial of 9MW2821 plus toripalimab is currently underway in China.

Previously, 9MW2821 was awarded a BTD as a monotherapy for la/mUC that has failed platinum-based chemotherapy and PD-(L)1 inhibitor therapy.²

BTD 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 of the NMPA, 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. The FDA also granted an orphan drug designation to the ADC for the treatment of esophageal cancer.

Data on 9MW2821 plus toripalimab

Mabwell also reported initial results from 40 patients with treatment-naïve la/mUC who received the combination of 9MW2821 plus toripalimab. Overall, the objective response rate (ORR) was 87.5%, and the confirmed ORR was 80%. Additionally, the disease control rate (DCR) was 92.5%. At the time of data collection, the median progression-free survival (PFS) and duration of response (DOR) had not yet been reached.

A pivotal phase 3 trial (NCT06592326) of 9MW2821 plus toripalimab vs chemotherapy in treatment-naïve la/mUC is currently underway in China. In total, the open-label, multicenter study plans to enroll 460 adult patients to assess the efficacy, safety, and immunogenicity of 9MW2821 plus toripalimab in the first-line setting in this patient population.³

To be eligible for enrollment, patients need to have previously untreated and histologically confirmed la/mUC, at least 1 measurable lesion per RECIST v1.1, an ECOG performance status of 0 or 1, adequate tumor tissues and organ functions, and a life expectancy of more than 12 weeks. Additionally, patients must be aged 18 to 80 years and suitable for cisplatin/carboplatin-based chemotherapy.

Those enrolled in the study will be randomly assigned to receive 1.25 mg/kg 9MW2821 via IV infusion plus 240 mg IV toripalimab or to chemotherapy with either gemcitabine plus cisplatin or carboplatin.

The primary end points for the trial are PFS per blinded independent central review and overall survival. Secondary end points include ORR, DCR, DOR, safety, and immunogenicity. All outcomes will be assessed for up to 50 months.

The phase 3 study is currently enrolling patients, with primary completion expected in September 2027. Final completion is planned for December 2028.

In addition to the combination regimen trial, 9MW2821 is also under phase 3 investigation as a monotherapy in patients with la/mUC who received prior treatment with a PD-(L)1 inhibitor and platinum-containing chemotherapy. The study (NCT06196736) has an expected enrollment of 420 patients and is assessing the antitumor activity of 9MW2821 vs chemotherapy in this patient population. Primary completion of the trial is expected in December 2026.⁴

References

1. Mabwell's nectin-4 targeted ADC 9MW2821 combination therapy demonstrates 87.5% ORR and granted CDE Breakthrough Therapy Designation. News release. Mabwell. Published online and accessed January 9, 2025. https://www.mabwell.com/en/news_info/id-167.html

2. Mabwell's novel nectin-4 targeting ADC 9MW2821 granted Breakthrough Therapy Designation by China's NMPA. News release. Mabwell. August 12, 2024. Accessed January 9, 2025. https://www.mabwell.com/en/news_info/id-160.html

3. 9MW2821 in combination with toripalimab vs standard chemotherapy in locally advanced or metastatic urothelial cancer. ClinicalTrials.gov. Last updated September 19, 2024. Accessed January 9, 2025. https://clinicaltrials.gov/study/NCT06592326

4. A study to evaluate 9MW2821 versus chemotherapy in subjects with previously treated locally advanced or metastatic urothelial cancer. ClinicalTrials.gov. Last updated September 19, 2024. Accessed January 9, 2025. https://clinicaltrials.gov/study/NCT06196736