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The following is a summary of “9MW2821, a next-generation Nectin-4 targeting antibody-drug conjugate, in patients with advanced solid tumors: a first-in-human, open-label, multicenter, phase Ⅰ/Ⅱ study,” published in the April 2025 issue of the Annals of Oncology by Zhang et al.

This first-in-human, open-label, multicenter study evaluated the safety, tolerability, and preliminary antitumor activity of 9MW2821, a next-generation monoclonal ADC targeting Nectin-4 and delivering monomethylauristatin E (MMAE), in patients with advanced solid tumors. The study was conducted in three phases: dose escalation, dose expansion, and cohort expansion. Patients who are eligible had histologically confirmed advanced solid tumors and had progressed following at least one prior line of systemic therapy. 9MW2821 was administered intravenously at doses ranging from 0.33 mg/kg to 1.5 mg/kg on days 1, 8, and 15 of each 28-day cycle. The primary objectives were to assess the treatment’s safety profile and preliminary clinical efficacy (ClinicalTrials.gov identifier: NCT05216965; CTR20220106).

Between June 11, 2022, and April 3, 2024, a total of 274 patients were enrolled. The study population included 51 patients with urothelial cancer, 62 with cervical cancer, 49 with esophageal cancer, 20 with triple-negative breast cancer, and 92 patients with other solid tumors. During the dose escalation phase, one DLT was observed in the 1.5 mg/kg group, consisting of Grade 4 neutropenia persisting for more than five days. Although the MTD was not reached, the recommended Phase II dose (RP2D) was established at 1.25 mg/kg, based on an optimal balance of safety and antitumor activity.

In the 1.25 mg/kg group, the most frequent treatment-related adverse events of Grade ≥3 severity were decreased neutrophil count, decreased white blood cell (WBC) count, anemia, elevated gamma-glutamyl transferase (GGT), rash, and peripheral sensory neuropathy. Among the 226 patients evaluable for efficacy, ORRs were 54.1% in urothelial cancer, 32.1% in cervical cancer, 14.0% in esophageal cancer, and 50% in triple-negative breast cancer, indicating promising antitumor activity across multiple tumor types.

In conclusion, 9MW2821 demonstrated a manageable safety profile and encouraging antitumor efficacy in patients with advanced solid tumors, particularly in urothelial, cervical, esophageal, and triple-negative breast cancers. Ongoing pivotal trials aim to further characterize its therapeutic potential and support future regulatory submissions.

Source: annalsofoncology.org/article/S0923-7534(25)00169-3/abstract