FDA Awards Fast Track Designation to 9MW2821 for Advanced ESCC


The FDA granted fast track designation to 9MW2821 for potential use in advanced, recurrent, or metastatic esophageal squamous cell carcinoma.



The FDA has granted fast track designation to the Nectin-4–directed antibody-drug conjugate (ADC) 9MW2821 for the treatment of patients with advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC).1

Nectin-4 is an adhesion molecule that is expressed on various solid tumors, making it a potential therapeutic target.2 9MW2821 is designed to specifically target Nectin-4 on the surface of the cell membrane following injection. After being internalized, the agent releases its cytotoxic payload, leading to the apoptosis of tumor cells.1

Findings from a phase 1/2 trial (NCT05216965) showed that patients with esophageal cancer treated with 9MW2821 monotherapy at a dose of 1.25 mg/kg (n = 30) experienced an overall response rate (ORR) of 30% and a disease control rate (DCR) of 73.3%. Notably, most of these patients (n = 28) underwent prior treatment with chemotherapy and immunotherapy.

The study is enrolling patients between 18 and 80 years of age with histologically or cytologically confirmed advanced malignant solid tumors, except for sarcoma. Patients need to have an ECOG performance status of 0 or 1; a life expectancy of at least 3 months; measurable disease according to RECIST v1.1 criteria; and adequate organ function. Notably, patients in the cohort expansion portion of the study are required to submit tumor tissue for Nectin-4 expression.3

Patients are excluded if they received chemotherapy or radiotherapy within 21 days prior to the first dose of study drug; any other anticancer therapy within 14 days prior to the first dose of study drug; underwent major surgery within 28 days prior to first dose of study drug; or received prior treatment with a Nectin-4–targeted ADC with a monomethyl auristatin E payload.

All patients are receiving intravenous 9MW2821 on days 1, 8, and 15 of each 28-day cycle. Incidence of adverse effects (AEs) is serving as the trial’s primary end point. Secondary end points include ORR, DCR, duration of response, time to response, progression-free survival, overall survival, and pharmacokinetics.

Enrollment in the phase 1/2 trial is ongoing.1

Prior data from this trial were also presented at the 2023 ESMO Congress, which showed that evaluable patients who were treated with 9MW2821 at a dose of at least 1.25 mg/kg (n = 39) experienced an ORR of 38.5%, a confirmed ORR of 33.3%, and a DCR of 84.6%.2

In the overall population (n = 97), tumor types included urothelial cancer (40%), cervical cancer (30%), breast cancer (7%), esophagus cancer (6%), and other (27%).

Regarding safety, previous data from the phase 1 study showed that 63.5% of patients treated at 1.25 mg/kg (n = 85) experienced any-grade treatment-related AEs (TRAEs), including 35.3% of patients who encountered a grade 3 or higher TRAE. Serious TRAEs were reported in 16.5% of patients. The rates of treatment interruption, reduction, and discontinuation due to TRAEs were 28.2%, 3.5%, and 1.2%, respectively.

Additional studies are planned to investigate 9MW2821. A phase 3 trial (NCT06196736) will evaluate 9MW2821 monotherapy vs chemotherapy in patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1/PD-L1 inhibitor and platinum-containing chemotherapy. A phase 1/2 trial (NCT06079112) will explore the combination of 9MW2821 and toripalimab-tpzi (Loqtorzi) in patients with locally advanced or metastatic urothelial cancer.1

Mabwell also announced that a phase 2 study of 9MW2821 monotherapy in patients with cervical cancer is planned.


  1. FDA grants fast track designation to 9MW2821. News release. Mabwell. February 25, 2024. Accessed February 27, 2024. https://www.mabwell.com/en/news_info/id-134.html
  2. Zhang J, Liu R, Gao S, et al. Preliminary results from a phase I/II study of 9MW2821, an antibody-drug conjugate targeting nectin-4, in patients with advanced solid tumors. Ann Oncol. 2023;34(suppl 2):S464. doi:10.1016/j.annonc.2023.09.1845
  3. A clinical study of 9MW2821 in subjects with advanced malignant solid tumors. ClinicalTrials.gov. Updated June 15, 2022. Accessed February 27, 2024. https://clinicaltrials.gov/study/NCT05216965
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