Bulumtatug Fuvedotin Yields 32% ORR as First Nectin-4 ADC With Data in Cervical Cancer

Treatment with bulumtatug fuvedotin (9MW2821) resulted in a confirmed objective response rate (ORR) of 32.08% (n = 17; 95% CI, 19.92%-46.32%), median duration of response (DOR) of 5.98 months (range, 3.58-9.10), and disease control rate (DCR) of 81.13% (n = 43; 95% CI, 68.03%-90.56%) with a safety profile that was largely characterized by hematologic toxicity in patients with recurrent or metastatic cervical cancer, according to updated data from a phase 1/2 trial (NCT05216965) that were presented at the 2026 ESMO Gynecological Cancers Congress.¹

Within the evaluable-analysis set (n = 53) the confirmed complete and partial response (PR) rates were 2.70% (n = 1) and 30.19% (n = 16), respectively; stable disease (SD) was seen in 49.06% (n = 26) of patients. The median time to response (TTR) was 1.9 months (range, 1.70-2.10).

In the post immunotherapy cohort (n = 31) the confirmed ORR was 29.03% (n = 9; 95% CI, 14.22%-48.04%) which consisted solely of PRs; SD was seen in 48.39% (n = 15) of patients. The DCR was 77.42% (n = 24; 95% CI, 58.90%-90.41%) and the median DOR was 9.10 months (range, 3.58-10.09). The median TTR was 2.1 months (range, 1.70-3.9).

“Bulumtatug fuvedotin is the first Nectin-4-targeting ADC to read out preliminary clinical data in cervical cancer worldwide, with a full peptide in recurrent or metastatic cervical cancer treatment,” Professor Huijuan Yang, presenting study author and faculty in the Department of Gynecologic Oncology at Fudan University Shanghai Cancer Center in China, said in the presentation.

What was the focus of the phase 1/2 trial?

Bulumtatug fuvedotin is a next-generation, Nectin-4-directed antibody-drug conjugate (ADC) with an MMAE payload. Preliminary results in several solid tumors suggest that the ADC may be able to offset the historically poor outcomes tied to treatment options in the second line and beyond setting of recurrent or metastatic cervical cancer.

In this analysis, investigators presented the full results from the study, which had originally reported an unconfirmed ORR of 40.54% as second- or third-line treatment in women with recurrent or metastatic cervical cancer (n = 37).²

The multicenter, open-label, single-arm trial enrolled patients with recurrent or metastatic cervical cancer that had progressed on or after platinum-based chemotherapy with or without bevacizumab (Avastin).¹ No more than 2 prior lines of systemic therapy were allowed. Patients also had to have an ECOG performance status of 0 or 1 and Nectin-4 positivity, which was quantified by immunohistochemical staining of 1+, 2+, or 3+.

Patients received bulumtatug fuvedotin at 1.25 mg/kg on days 1, 8, and 15 every 28 days until disease progression, unacceptable toxicity, or 2 years of treatment had passed.

The primary end point was investigator-assessed ORR per RECIST 1.1 criteria. Secondary end points included progression-free survival (PFS), DOR, DCR, time to response, and overall survival (OS).

At the May 20, 2025, data cutoff, 55 patients had received at least 1 dose of bulumtatug fuvedotin. Median follow-up was 21.26 months (range, 2.79-28.68).

Baseline characteristics revealed that the median age was 52.5 years (range, 33-74). Represented histologies included squamous cell (n = 46; 83.64%), adenocarcinoma (n = 8; 14.55%), and adenosquamous carcinoma (n = 1; 1.81%). ECOG performance status was predominantly 1 (n = 46; 83.64%) as opposed to 0 (n = 9; 16.36%). Patients had received either 1 (n = 31; 56.36%) or 2 (n = 24; 43.64%) prior lines of therapy, which included bevacizumab in 49.09% (n = 27) of cases and anti–PD(L)1 therapy in 58.18% (n = 32).

The majority of patients (n = 39; 73.6%) of all treated patients had a reduction in target lesion size that proved durable.

How did bulumtatug fuvedotin perform in patients previously treated with immunotherapy?

The median PFS was 3.9 months (95% CI, 3.7-5.6) in the evaluable-analysis set and 4 months (95% CI, 3.6-9.2) in the post immunotherapy population. In the former, the 6- and 12-month PFS rates were 31.9% (95% CI, 19%-45.6%) and 19.9% (95% CI, 9.1%-33.7%), respectively. In the latter, the 6- and 12-month PFS rates were 34.7% (95% CI, 17.7%-52.4%) and 24.8% (95% CI, 10%-43%), respectively.

The median OS was 19.4 months (95% CI, 15.7-not reached [NR]) in the evaluable-analysis set and NR (95% CI, 15.2 months-NR) in the post immunotherapy population. In the former, the 6- and 12-month OS rates were 72.7% (95% CI, 58.3%-82.9%) and 49.1% (95% CI, 33.7%-62.8%), respectively. In the latter, the 6- and 12-month OS rates were 76.6% (95% CI, 57.1%-88.1%) and 51.1% (95% CI, 30.1%-68.7%), respectively.

How was the safety profile characterized and what comes next?

With respect to safety, no treatment-related deaths occurred, nor were any new signals observed. Treatment-related adverse effects (TRAEs) occurred in all patients and the most common, in order of frequency, were leukopenia (n = 44; 80%), anemia (n = 38; 69.09%), neutropenia (n = 36; 65.45%), increased aspartate aminotransferase levels (n = 36; 65.45%), increased alanine aminotransferase levels (n = 36; 65.45%), alopecia, decreased appetite, rash, thrombocytopenia, nausea, asthenia, hypertriglyceridemia, hyperglycemia, decreased weight, vomiting, hypercholesterolemia, increased gamma-glutamyl transferase levels, and hypoesthesia.

“We saw manageable safety with tolerance that is consistent with ADC class expectations,” Yang reported.

Grade 3 or greater TRAEs occurred in 70.91% (n = 39) of patients and serious TRAEs occurred in 27.27% (n = 15). TRAEs that led to interruption (n = 42; 76.36%), dose reduction (n = 15; 27.27%), or discontinuation (n = 2; 3.64%) were all reported.

“Further investigation includes the world’s first phase 3 confirmatory trial [NCT06692166] comparing bulumtatug fuvedotin vs chemotherapy in recurrent or metastatic cervical cancer,” Yang concluded.³

Disclosures: Yang had no competing interests to disclose for the study.

References

1. Yang H, Zhang J, Liu R, et al. Bulumtatug fuvedotin (BFv, 9MW2821), a nectin-4 antibody-drug conjugate, in patients with recurrent or metastatic cervical cancer: updated results from a phase I/II study. Presented at: 2026 ESMO Gynaecological Cancers Congress; June 17-19, 2026; Copenhagen, Denmark. Abstract 28RO.
2. SGO 2024 | the first published clinical data of Nectin-4-targeting ADC developed by Mabwell in cervical cancer demonstrates its outstanding therapeutic potential. News release. Mabwell. March 19, 2024. Accessed June 17, 2026. https://www.mabwell.com/en/news_info/id-139.html
3. A study to evaluate 9MW2821 versus treatment of physician’s choice for subjects with recurrent or metastatic cervical cancer. ClinicalTrials.gov. Updated November 22, 2024. Accessed June 17, 2026. https://clinicaltrials.gov/study/NCT06692166