bulumtatug fuvedotin (9MW2821) / Mabwell (Shanghai) Biosci - LARVOL DELTA

Bulumtatug Fuvedotin (BFv; 9MW2821), a novel Nectin-4 antibody-drug conjugate(ADC), combined with Toripalimab in patients with locally advanced or metastatic urothelial carcinoma(la/mUC): Follow-up results from a phase 1b/2 study. [WITHDRAWN] (ESMO 2025) - No abstract available

Clinical • Metastases • P1/2 data • Oncology • Solid Tumor • Urothelial Cancer

Antibody-drug conjugates targeting the cadherin, claudin and nectin families of adhesion molecules. (PubMed, Front Mol Med) - "Enfortumab vedotin is an NECTIN4-targeting antibody-drug conjugate that is approved for the treatment of urothelial cancer, whereas other ADCs or derivatives that target NECTIN4, such as bulumtatug fuvedotin, SHR-A2102 and zelenectide pevedotin, are being studied in randomized phase III clinical trials. In contrast, arcotatug tavatecan, garetatug rezetecan, sonesitatug vedotin and tecotabart vedotin are anti-CLDN18.2 ADCs in phase III clinical trials for the treatment of CLDN18.2-positive gastric or gastroesophageal junction adenocarcinomas, and raludotatug deruxtecan is an anti-CDH6 ADC in a phase II/III clinical trial for the treatment of platinum-resistant ovarian cancer. ADCs that target cell-cell adhesion molecules are a rapidly emerging class of cancer therapeutics, and bispecific ADCs and longitudinal companion diagnostics are emerging to further improve the clinical benefits of conventional ADCs."

Journal • Review • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Genito-urinary Cancer • Oncology • Ovarian Cancer • Solid Tumor • Urothelial Cancer • CDH17 • CDH6 • CLDN18 • CLDN6

Structural basis of nectin-4 recognition by the antibody-drug conjugate 9MW2821. (PubMed, J Biol Chem) - "Based on the structure of nectin-4 D1/9MW2821 Fab complex resolved in this study, we have elucidated the molecular mechanism of 9MW2821 in cancer therapy. The findings provide a basis for optimizing future monoclonal antibodies targeting nectin-4."

Journal • Oncology • Solid Tumor • NECTIN1 • NECTIN4 • TIGIT

JS207 Combination Therapy in Triple-negative Breast Cancer (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: Shanghai Junshi Bioscience Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1

A Dose Randomization Study of Bulumtatug Fuvedotin in TNBC Patients Previously Treated With ADCs (clinicaltrials.gov) - P1 | N=52 | Recruiting | Sponsor: Mabwell (Shanghai) Bioscience Co., Ltd. | Not yet recruiting ➔ Recruiting | Initiation date: May 2025 ➔ Aug 2025

Enrollment open • Trial initiation date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Mabwell Announces First Patient Dosed in the US Clinical Study of Bulumtatug Fuvedotin in TNBC Patients Previously Treated with ADCs (PRNewswire) - "The multicenter clinical study (NCT06908928) aims to evaluate the efficacy and safety of BFv in TNBC patients previously treated with a taxane and an antibody-drug conjugate with a topoisomerase inhibitor payload. The first subject has been dosed at Memorial Sloan Kettering Cancer Center."

Trial status • Triple Negative Breast Cancer

JS207 Combination Therapy in Triple-negative Breast Cancer (clinicaltrials.gov) - P2 | N=80 | Not yet recruiting | Sponsor: Shanghai Junshi Bioscience Co., Ltd.

New P2 trial • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1

Highlights in Oral Presentation of Mabwell's 9MW2821 at 2025 ASCO (The Manila Times) - P1/2 | N=100 | NCT06079112 | Sponsor: Mabwell (Shanghai) Bioscience Co., Ltd. | "The Objective Response Rate (ORR) was 87.5% (95% CI: 73.2, 95.8), confirmed ORR was 80%, complete response (CR) rate was 12.5%, Disease Control Rate (DCR) was 92.5% (95% CI: 79.6, 98.4). 97.5% of assessable patients had tumor reduction, 57.5% of assessable patients had tumor reduction of 50% above. The ORR in selected subgroups was consistent with results in overall population. Different subgroups of treatment-naive patients could benefit from BFv and Toripalimab regardless of primary tumor site, liver metastasis, expression of Nectin-4 and PD-L1. The ORR was 100% (24/24) in patients older than 65, 94.44% (17/18) in patients with tumor primary site at lower urinary tract, 83.33% (5/6) in patients with liver metastasis, 100% (7/7) in nectin-4 negative patients, and 100% (8/8) in PD-L1 positive patients."

P1/2 data • Urothelial Cancer

9MW2821, a novel Nectin-4 antibody-drug conjugate (ADC), combined with toripalimab in treatment-naïve patients with locally advanced or metastatic urothelial carcinoma (la/mUC): Results from a phase 1b/2 study. (ASCO 2025) - P1/2, P3 | "9MW2821 combined with Toripalimab in treatment-naïve patients with la/mUC demonstrated remarkable efficacy and well-tolerated safety profile. A pivotal phase 3 study is ongoing currently. Clinical trial identification: NCT06592326."

Clinical • Metastases • P1/2 data • Bladder Cancer • Breast Cancer • Cervical Cancer • Esophageal Cancer • Oncology • Solid Tumor • Urothelial Cancer • NECTIN4

9MW2821 Combined With Other Antitumor Drugs in Patients With Advanced Gynecological Tumors (clinicaltrials.gov) - P1/2 | N=260 | Not yet recruiting | Sponsor: Mabwell (Shanghai) Bioscience Co., Ltd.

New P1/2 trial • Gynecologic Cancers • Oncology

Mabwell to Present Clinical Data of 9MW2821 Combined with Toripalimab in Patients with UC in an Oral Presentation at 2025 ASCO (PRNewswire) - "Mabwell...announced that the Phase Ib/II clinical study results of the novel Nectin-4-targeting ADC 9MW2821 combined with toripalimab in patients with locally advanced or metastatic urothelial carcinoma will be presented in an oral presentation at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago, USA, May 30-June 3, 2025. Clinical data from 3 ADC clinical studies will also be published as poster presentations at the meeting."

Clinical data • Urothelial Cancer

A Clinical Study of 9MW2821 Monotherapy or Combined With Other Anticancer Therapy in Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=188 | Not yet recruiting | Sponsor: Mabwell (Shanghai) Bioscience Co., Ltd.

Monotherapy • New P1/2 trial • Oncology • Solid Tumor

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 (Ann Oncol) - P1/2 | N=208 | NCT05216965 | Sponsor: Mabwell (Shanghai) Bioscience Co., Ltd. | "Between June 11, 2022, and Apr 3, 2024, 274 patients were enrolled, including 51 with urothelial cancer, 62 with cervical cancer, 49 with esophageal cancer, 20 with triple negative breast cancer and 92 with other solid tumors. In dose escalation phase, one dose limiting toxicity was observed in 1.5mg/kg group, which was grade 4 neutropenia lasted more than 5 days. Maximum tolerated dose of 9MW2821 was not reached....Among 226 patients evaluable for efficacy, objective response rates were 54.1%, 32.1%, 14.0% and 50% in urothelial cancer, cervical cancer, esophageal cancer and triple negative breast cancer, respectively."

P1/2 data • Cervical Cancer • Esophageal Cancer • Triple Negative Breast Cancer • Urothelial Cancer

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. (PubMed, Ann Oncol) - P1/2, P3 | "The results suggest that 9MW2821 was tolerable and clinically significant in efficacy in various types of solid tumors besides urothelial cancer. Several pivotal trials are currently in progress. (NCT06196736, NCT06592326, NCT06692166)."

Clinical • Journal • P1 data • Breast Cancer • Cervical Cancer • Esophageal Cancer • Genito-urinary Cancer • Hematological Disorders • Neutropenia • Oncology • Pain • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer • NECTIN4

9MW2821-2023-CP301: A Study to Evaluate 9MW2821 Versus Chemotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Urothelial Cancer (clinicaltrials.gov) - P3 | N=432 | Recruiting | Sponsor: Mabwell (Shanghai) Bioscience Co., Ltd. | Trial completion date: Dec 2028 ➔ Jul 2027 | Trial primary completion date: Dec 2026 ➔ Sep 2026

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

A Dose Randomization Study of Bulumtatug Fuvedotin in TNBC Patients Previously Treated With ADCs (clinicaltrials.gov) - P1 | N=52 | Not yet recruiting | Sponsor: Mabwell (Shanghai) Bioscience Co., Ltd.

New P1 trial • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

9MW2821 + Toripalimab vs 9MW2821 for 1st Line Locally Advanced or Metastatic Urothelial Carcinoma (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Mabwell (Shanghai) Bioscience Co., Ltd.

New P2 trial • Bladder Cancer • Kidney Cancer • Oncology • Solid Tumor • Urothelial Cancer

A Clinical Study of 9MW2821 (and PD-1 Inhibitor) in Locally Advanced or Metastatic Triple-Negative Breast Cancer (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: Mabwell (Shanghai) Bioscience Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Mabwell's Nectin-4 Targeted ADC 9MW2821 Combination Therapy Demonstrates 87.5% ORR and Granted CDE Breakthrough Therapy Designation (PRNewswire) - P3 | N=460 | NCT06592326 | Sponsor: Mabwell (Shanghai) Bioscience Co., Ltd. | "Mabwell...announced a significant milestone for its proprietary Nectin-4 targeted ADC (9MW2821). On January 8, 2025, 9MW2821 was granted Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in China. 9MW2821 is given in combination with toripalimab, an anti-PD-1 monoclonal antibody, for treatment-naïve, unresectable, locally advanced or metastatic urothelial carcinoma(la/mUC). Up to now, 40 treatment-naïve patients with la/mUC were enrolled and received the combination therapy. ORR was 87.5% (comfirmed ORR was 80%) and DCR was 92.5%. Median PFS and DoR were not reached....A pivotal Phase III study of 9MW2821 in combination with PD-1 is ongoing."

Breakthrough therapy • P3 data • Urothelial Cancer

Mabwell's Novel Nectin-4 Targeting ADC 9MW2821 Approved for 2 Clinical Trials by CDE of NMPA (PRNewswire) - "Mabwell...announced that its novel Nectin-4 targeting ADC (R&D code: 9MW2821) has received IND approval for two clinical studies. The first will explore its use in combination with a PD-1 monoclonal antibody in the treatment of perioperative urothelial carcinoma, while the second will investigate its combination with other antitumor agents for the treatment of advanced solid tumors....The recent approval of a multi-drug combination treatment program for cervical cancer and esophageal squamous cell carcinoma, along with the expansion of 9MW2821's indication to include the perioperative stage for urothelial carcinoma, is anticipated to significantly broaden the therapeutic reach of 9MW2821, potentially benefiting a larger patient population."

IND • Cervical Cancer • Esophageal Squamous Cell Carcinoma • Urothelial Cancer

A Study to Evaluate 9MW2821 Versus Treatment of Physician's Choice for Subjects With Recurrent or Metastatic Cervical Cancer (clinicaltrials.gov) - P3 | N=420 | Recruiting | Sponsor: Mabwell (Shanghai) Bioscience Co., Ltd.

Metastases • New P3 trial • Cervical Cancer • Oncology • Solid Tumor

9MW2821 in Combination With Toripalimab vs Standard Chemotherapy in Locally Advanced or Metastatic Urothelial Cancer (clinicaltrials.gov) - P3 | N=460 | Recruiting | Sponsor: Mabwell (Shanghai) Bioscience Co., Ltd.

Combination therapy • Metastases • New P3 trial • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

9MW2821-2023-CP301: A Study to Evaluate 9MW2821 Versus Chemotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Urothelial Cancer (clinicaltrials.gov) - P3 | N=420 | Recruiting | Sponsor: Mabwell (Shanghai) Bioscience Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

9MW2821 Combined With Toripalimab Injection in Subjects With Local Advanced or Metastatic Urothelial Cancer (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: Mabwell (Shanghai) Bioscience Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Maiwei Biopharma initiates Phase III clinical trial of Nectin-4 ADC+PD-1 in advanced urothelial carcinoma [Google translation] (Eastmoney.com) - "Recently, the clinical trials website showed that Mywell Biopharma has registered a Phase 3 clinical trial (NCT06592326) of the Nectin-4 ADC drug 9MW2821 combined with toripalimab and standard chemotherapy in the first-line treatment of locally advanced or metastatic urothelial carcinoma. This is a randomized, controlled, open-label, multicenter Phase 3 clinical study designed to evaluate the efficacy, safety, and immunogenicity of 9MW2821 combined with toripalimab and standard chemotherapy in first-line locally advanced or metastatic urothelial carcinoma."

Trial status • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer