Disitamab vedotin (Aidixi®; RemeGen; previously known as RC-48; see Drugmap), a novel HER2-targeted antibody-drug conjugate (ADC), has been granted approval by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) for its third indication of human epidermal growth factor receptor-2 (HER2-) positive advanced breast cancer with liver metastasis previously treated with trastuzumab (Herceptin®; Genentech/Roche) or its biosimilar and taxanes.*
The drug, developed by RemeGen is licenced to Pfizer/Seagen for worldwide commercialization outside of China. At the time of signing in August 2021, this agreement was valued at US $ 2.6 billion (an upfront payment of US $ 200 million, with an additional $2.4 billion tied to future development milestones across multiple cancer indications).
Disitamab vedotin combines the drug-linker technology originally developed by Pfizer/Seagen with RemeGen’s novel HER2 antibody exhibiting higher affinity and an increased internalization rate as compared to trastuzumab in preclinical models.** [1]
Ongoing studies
As monotherapy, disitamab vedotin has demonstrated anti-tumor activity in clinical trials in several solid tumor types, including urothelial, gastric and breast cancer, as well as across a spectrum of HER2 expression levels. In addition, promising combination activity was demonstrated with a PD-1 inhibitor in urothelial cancer. It is believed that vedotin-based immunogenic cell death (ICD) may differentiate this class of ADC’s when combined with checkpoint inhibitors.[2]
Disitamab vedotin has been approved by NMPA before for HER2-overexpressing locally advanced or metastatic gastric carcinoma previously treated with at least two lines of systemic chemotherapies and HER2 over-expressing locally advanced or metastatic urothelium carcinoma previously treated with platinum-based chemotherapies.
Common cancer
Breast cancer is one of the most common cancers in the world. In 2022, there were around 2.3 million new cases diagnosed and 67,000 death, and the disease risk is steadily rising each year.
Approximately 20%-25% breast cancer cases are HER2-positive. HER2 is an important cancer driver gene and serves as a prognostic indicator in breast cancer. HER2-positive breast cancer is highly aggressive and malignant, associated with rapid disease progression and poor prognosis.
Liver is one of the most common sites for breast cancer metastases. An average of 50% of patients diagnosed with metastatic breast cancer develop liver metastases, and approximately 5% to 12% of these patients develop such metastases as the main site of breast cancer recurrence.[3]
There was no standard of care (SOC) for HER2-positive breast cancer liver metastasis previously and exploring new treatment and improving patient benefit remain the research hotspots of breast cancer management. As a novel HER2-targeted ADC, disitamab vedotin can prolong the progression-free survival of HER2-positive breast cancer patients with liver metastasis and shows manageable safety.
Approval
The approval of disitamab vedotin was granted based on a phase 3 clinical trial (NCT03500380, study ID: RC48-C006). Detailed data has been presented in December, 2024 at the San Antonio Breast Cancer Symposium (SABCS).
The study results for this study confirmed that compared with lapatinib (Tykerb®; Novartis) plus capecitabine (Xeloda®; Genentec/Roche), disitamab vedotin significantly improved PFS and reduced the risk of disease progression or death by 44% (median PFS: 9.9 months vs. 4.9 months; HR=0.561, P=0.0143)
The study results also demonstrated that the overall survival (OS) data, though immature, indicated a benefit trend in favor of DV, with median OS of NE vs. 25.9 months (HR=0.56; 95%CI, 0.25-1.29), and showed a manageable safety profile with no new safety signal detected.
“It’s amazing that disitamab vedotin got approved for HER2-positive advanced breast cancer with liver metastasis in China. RC48-C006 is the first phase 3 clinical trial investigating a HER2-targeted ADC in patients with HER2-positive advanced breast cancer, and the results were encouraging,” noted Professor Jiayu Wang MD, Ph.D, from the Cancer Hospital, Chinese Academy of Medical Sciences, the sub-investigator of the RC48-C006 study.
“In 2021, disitamab vedotin was granted breakthrough therapy designation by NMPA for this indication. The approval this year means a new treatment option for this population in China and a step forward in clinical practice.,” Wang added.
“I sincerely hope more therapeutic options from RemeGen will be available for patients with refractory advanced breast cancer.” observed Professor Jiayu Wang from the Cancer Hospital, Chinese Academy of Medical Sciences, the sub-investigator of the RC48-C006 study,” Wang said.
Huge unmet clinical needs
“Breast cancer poses a significant threat to global health with huge unmet clinical needs. As the first and only approved ADC for HER2-positive BCLM, DV represents a new regimen with favorable efficacy and manageable safety profile, which I believe is a valuable breakthrough,” Jianmin Fang, Chief Executive Officer of RemeGen.
“I [] appreciate the clinical research team and all participants for their hard work and cooperation. Meanwhile, promising efficacy and manageable safety profile of DV were also observed in other clinical trials on breast cancer with different HER2 expression levels, and we are also evaluating the efficacy and safety of several DV combination therapy options to expand its indication and benefit more patients.” Fang concluded.
The approval of DV provides solid evidence for clinical decision-making and brings better treatment option for the target patients.
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Note: * RemeGen has implemented a differentiated development and commercial strategy for disitamab vedotin, including gastric cancer, urothelial carcinoma, breast cancer, and other HER2-expressing cancers.
** Disitamab vedotin comprising a monoclonal antibody against human epidermal growth factor receptor 2 (HER2) conjugated via a cleavable linker to the cytotoxic agent monomethyl auristatin E (MMAE).
Clinical trials
A Study of RC48-ADC Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer With or Without Liver Metastases – ClinicalTrials.gov ID NCT03500380
A Study of Disitamab Vedotin in Adults With HER2 Expressing Advanced Breast Cancer – ClinicalTrials.gov ID NCT06966453
A Study of RC48-ADC(Antibody Drug Conjugate) and JS001 to Evaluate the Safety and Pharmacokinetics of Subjects With Locally Advanced or Metastatic Urothelial Cancer – ClinicalTrials.gov ID NCT04264936
Highlights of Prescribing Information
Trastuzumab (Herceptin®; Genentech/Roche)[Prescribing Information]
Lapatinib (Tykerb®; Novartis)[Prescribing Information]
Capecitabine (Xeloda®; Genentec/Roche)[Prescribing Information]
Reference
[1] Yao X, Jiang J, Wang X, Huang C, Li D, Xie K, Xu Q, Li H, Li Z, Lou L, Fang J. A novel humanized anti-HER2 antibody conjugated with MMAE exerts potent anti-tumor activity. Breast Cancer Res Treat. 2015 Aug;153(1):123-33. doi: 10.1007/s10549-015-3503-3. Epub 2015 Aug 8. PMID: 26253944.
[2] Zhu K, Chang Y, Zhao D, Guo A, Cao J, Wu C, Guan Y, Ding S. Expression of HER2 in high-grade urothelial carcinoma based on Chinese expert consensus and the clinical effects of disitamab vedotin-tislelizumab combination therapy in the treatment of advanced patients. Front Pharmacol. 2024 Feb 22;15:1355081. doi: 10.3389/fphar.2024.1355081. PMID: 38455962; PMCID: PMC10918465.
[3] Liver Metastasis. Breastcancer.org. Online. Last accesses on may 9, 2025.
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