Mabwell (Shanghai) Bioscience recently received the National Medical Products Administration (NMPA) approval for its 9MW2821, a novel Nectin-4 targeting ADC, to enter Phase 2 clinical trial in China.
Mabwell’s investigational ADC, 9MW2821, is a new generation site-specific conjugated novel nectin-4-targeting ADC and is the first drug candidate to enter clinical study among the nectin-4-targeting ADCs developed by Chinese companies. The Phase 2 clinical trial aims to evaluate the efficacy and safety of 9MW2821 as monotherapy or in combination in patients with locally advanced or metastatic TNBC.
The new study includes two cohorts.
- Cohort A enrolls patients with locally advanced or metastatic TNBC who have previously received taxane/anthracycline-based chemotherapy and topoisomerase inhibitor based antibody-drug conjugate treatment, and will receive 9MW2821 monotherapy
- Cohort B enrolls patients with locally advanced or metastatic TNBC who have not previously received systemic therapy, and will receive a combination treatment of 9MW2821 and a PD-1 inhibitor.
9MW2821 delivers monomethyl auristatin E (MMAE) to cells expressing Nectin-4, an clinically validated adhesion molecule that highly expressed in variety of solid tumors, especially urothelial cancer (UC), cervical cancer (CC), esophageal cancer (EC) and breast cancer.
Preliminary data
The preliminary clinical results of the Phase 1 / 2 study presented at the 2024 annual meeting of the American Society of Clinical Oncology (ASCO) demonstrated promising efficacy in patients treated for variety of advanced or metastatic solid tumors, especially urothelial cancer (UC), cervical cancer (CC), esophageal cancer (EC) and triple negative breast cancer (TNBC).[1]
The study, a first-in-human, open-label, dose-escalation and cohort expansion study. was designed to characterize the safety, tolerability, pharmacokinetics, preliminary anti-tumor activity and immunogenicity of 9MW2821 administered by intravenous (IV) infusion.
By gaining approval for the Phase 2 trial, the company leads the development of nectin-4 ADCs in China, offering new hope to Chinese patients. This is the conclusion of Nadim Anwer, a Pharma Analyst at leading data and analyticals GlobalData.
Poor prognosis
TNBC is the most aggressive type of breast cancer, with a higher risk of recurrence and a poor prognosis. Advanced TNBC is not responsive to targeted or endocrine therapies, and chemotherapy remains the standard treatment for advanced TNBC in China. According to GlobalData’s Pharma Intelligence Center, the number of incident cases of TNBC in China is expected to increase at a compound annual growth rate (CAGR) of 2.5% from 59,625 in 2023 to 67,586 in 2028.
“There is a significant unmet need for novel therapeutics among metastatic TNBC patients in China due to limited treatment options compared to other breast cancer subtypes. TNBC tends to grow and spread faster than other types of invasive breast cancer, so it is traditionally considered the most difficult breast cancer type to treat. 9MW2821, the next generation ADC, could positively impact the metastatic TNBC treatment landscape in China,” Anwer explained.
The clinical results showed an overall response rate of 50.0% and a disease control rate of 80.0% in 20 evaluable patients with locally advanced or metastatic TNBC. The median progression-free survival was 5.9 months and one patient achieved a complete response (CR) and maintained CR for 20 months. The safety profile showed adequate tolerability. In addition, 9MW2821 was recently granted a fast-track designation by the USFDA.
Nectin-4 targeting ADCs
As per GlobalData’s Pharma Intelligence Center, there are only two Nectin-4-targeting ADC in clinical development in China for TNBC, which includes Mabwell’s asset.
The second asset, SYS6002 (CRB-701), is being developed CSPC Pharmaceutical and Corbus Pharmaceuticals. This investigational ADC is also a next-generation ADC targeting Nectin-4 and includes a site-specific cleavable linker with a homogenous drug antibody ratio of 2. SYS6002 (CRB-701), which uses MMAE as the payload, is in Phase 1 clinical development for TNBC and is being investigated in a dose escalation on a Q3W schedule, with a view to reducing free-MMAE concentrations in plasma, reducing the associated toxicities that are known to dose limit enfortumab vedotin (Padcev®; Astellas Pharma and Pfizer), the only approved Nectin-4 ADC. [2]
First in China
“The R&D progress of 9MW2821 ranks in the forefront among ADCs with the same target in the world, which reflects our strength in the development of innovative drugs. By virtue of experienced team and strong R&D strength in the industry, Mabwell has established several leading international R&D platforms, including ADC development platforms,” noted Dr. Liu Datao, co-founder and Chief Executive Officer of Mabwell.
“9MW2821 is expected to be the first nectin-4 ADC for TNBC in China, if successful in clinical trials and following approvals,” GlobaData’s Nadim Anwer added..
“Mabwell’s promising asset would bring a significant shift in current treatment approaches for metastatic TNBC as a first-line treatment, and with a larger patient population, it would generate lucrative sales. Mabwell would like to strengthen its position with differentiated innovation for metastatic TNBC, making it difficult for competitors. Notably, with an innovative asset, the company can attract and expand its strategic collaborations with foreign players,” Anwer concluded.
United States: Fast Track Development
In the United States the Food and Drug Administration (FDA) granted Fast Track Development status to 9MW2821 to facilitate the expedited development of the drug for the treatment of advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC). In February and May 2024, the FDA also granted Orphan Drug Designation and Fast Track Development status for the treatment of esophageal cancer and recurrent or metastatic cervical cancer progressed on or following prior treatment with a platinum-based chemotherapy regimen. Finally, earlier this month, the FDA granted Fast Track Development status for the treatment of locally advanced or metastatic Nectin-4 positive TNBC.
Clinical trials
A Clinical Study of 9MW2821 in Subjects With Advanced Malignant Solid Tumors – ClinicalTrials.gov ID NCT05216965
Highlights of prescribing information
Enfortumab vedotin (Padcev®; Astellas Pharma and Pfizer) [Prescribing Information]
Reference
[1] Jian Zhang et al., 9MW2821, a nectin-4 antibody-drug conjugate (ADC), in patients with advanced solid tumor: Results from a phase 1/2a study.. JCO 42, 3013-3013(2024).
DOI:10.1200/JCO.2024.42.16_suppl.3013
[2] Ding-Wei Ye et al., Clinical update related to the first-in-human trial of SYS6002 (CRB-701), a next-generation nectin-4 targeting antibody drug conjugate.. JCO 42, 3151-3151(2024). DOI:10.1200/JCO.2024.42.16_suppl.3151
Featured image: © 2016 – 2024 Fotolia/Adobe. Used with permission.
DOI: 10.14229/jadc.2024.07.26.002
