Phase 3 trial launches of 9MW2821 plus toripalimab for urothelial carcinoma

Patient enrollment has begun in a phase 3 trial (NCT06196736) of the investigational nectin-4 targeting antibody drug conjugate (ADC) 9MW2821 in combination with toripalimab vs standard chemotherapy for the first-line treatment of patients with locally advanced or metastatic urothelial cancer, Mabwell announced in a news release.¹

Primary completion of the study is anticipated for December 2026.

The phase 3 study of the ADC was approved by the Center for Drug Evaluation of China’s National Medical Products Administration (NMPA) in December 2023. The trial initiation comes on the heels of China’s NMPA granting a breakthrough therapy designation to 9MW2821 in August 2024 for patients with locally advanced or metastatic urothelial carcinoma that progressed after previous platinum-based chemotherapy and PD-(L)1 inhibitor therapy.

In total, the phase 3, open-label study plans to enroll 420 adult patients with locally advanced or metastatic urothelial carcinoma to assess the anti-tumor activity of 9MW2821 plus toripalimab vs chemotherapy.²

To be eligible for enrollment in the trial, patients must have measurable disease per RECIST v1.1, an ECOG performance status of 0 or 1, adequate organ function, and a life expectancy of at least 12 weeks.

For the trial, patients will be randomly assigned to receive either 1.25 mg/kg of 9MW2821 by intravenous infusion on days 1, 8, and 15 of every 28-day cycle or to investigator’s choice of chemotherapy given by intravenous infusion on day 1 of every 21-day cycle. Chemotherapy may either be 75 mg/m2 docetaxel or 175 mg/m2 paclitaxel.

The dual primary end points for the trial are progression-free survival (PFS) per blinded independent central review and overall survival (OS), as assessed for up to 3 years. Secondary end points include objective response rate (ORR), duration of response (DOR), time to response (TTR), disease control rate (DCR), and the incidence of adverse events (AEs).

Primary completion of the study is anticipated for December 2026, with final completion expected in December 2028.

The combination of 9MW2821 plus toripalimab is also being assessed in an ongoing phase 1b/2 trial (NCT06079112).³ In total, the trial is enrolling 100 patients to assess the safety, tolerability, initial efficacy, pharmacokinetics, and immunogenicity of the combination in patients with locally advanced or metastatic urothelial carcinoma. The first patient in the trial was dosed in September 2023.

The primary outcome measures for the study are the incidence of AEs and serious AEs. Secondary outcome measures include ORR, DOR, TTR, DCR, PFS, and OS, all assessed for up to 1 year.

Primary completion of the trial is expected in December 2026.

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.^4,5

Overall, data showed that 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 triple negative breast cancer. All patients were treated with 9MW2821 at the recommended phase 2 dose level of 1.25 mg/kg.

References

1. Mabwell announces CDE approval to initiate phase III clinical trial of 9MW2821 for urothelial carcinoma in combination with PD-1 inhibitor. News release. Mabwell. Published online and accessed August 26, 2024. https://www.prnewswire.com/news-releases/mabwell-announces-cde-approval-to-initiate-phase-iii-clinical-trial-of-9mw2821-for-urothelial-carcinoma-in-combination-with-pd-1-inhibitor-302230453.html

2. 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 26, 2024. https://clinicaltrials.gov/study/NCT06196736

3. 9MW2821 combined with toripalimab injection in subjects with local advanced or metastatic urothelial cancer. ClinicalTrials.gov. Last updated October 12, 2023. Accessed August 26, 2024. https://clinicaltrials.gov/study/NCT06079112

4. 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

5. Mabwell announces 9MW2821 clinical data and latest progress to be presented at 2024 ASCO Annual Meeting. News release. Mabwell. May 24, 2024. Accessed August 26, 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