Mabwell, a biopharmaceutical company, has achieved a significant regulatory milestone with its Nectin-4 targeted antibody-drug conjugate (ADC), 9MW2821. The Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) granted Breakthrough Therapy Designation (BTD) to 9MW2821 on January 8, 2025, for use in combination with toripalimab in treatment-naïve, unresectable, locally advanced or metastatic urothelial carcinoma (la/mUC).
The BTD is designed to expedite the development and review of promising therapies for serious diseases, offering prioritized engagement with the CDE and accelerated approval pathways. This designation highlights the potential of 9MW2821 to address unmet needs in urothelial carcinoma treatment.
Promising Early Clinical Data
Clinical data from 40 treatment-naïve patients with la/mUC who received the 9MW2821 and toripalimab combination showed an encouraging objective response rate (ORR) of 87.5%, with a confirmed ORR of 80%. 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.
Ongoing Phase III Trial
A pivotal Phase III trial (NCT06592326) is currently underway in China, evaluating 9MW2821 in combination with toripalimab versus chemotherapy as a first-line treatment for la/mUC. The open-label, multicenter study plans to enroll 460 adult patients to assess the efficacy, safety, and immunogenicity of the combination therapy. Patients will be randomized to receive either 1.25 mg/kg of 9MW2821 plus 240 mg of toripalimab or chemotherapy (gemcitabine plus cisplatin or carboplatin).
The primary endpoints of the trial are PFS per blinded independent central review and overall survival. Secondary endpoints include ORR, DCR, DOR, safety, and immunogenicity. The study is expected to be completed by December 2028.
Prior Breakthrough Therapy Designation
Previously, 9MW2821 received BTD as a monotherapy for la/mUC that had progressed following platinum-based chemotherapy and PD-(L)1 inhibitor therapy, underscoring its potential as a treatment option in later lines of therapy.
Additional Studies
9MW2821 is also being investigated in a Phase III monotherapy trial (NCT06196736) for patients with la/mUC who have previously been treated with a PD-(L)1 inhibitor and platinum-containing chemotherapy. This study aims to enroll 420 patients and is comparing the antitumor activity of 9MW2821 versus chemotherapy, with an expected primary completion date of December 2026.
