Aidixi (disitamab vedotin)

P2, N=172, Recruiting, Seagen, a wholly owned subsidiary of Pfizer | Trial completion date: Jan 2030 --> Jul 2029 | Trial primary completion date: Jan 2030 --> Jul 2029

P2, N=172, Recruiting, Seagen, a wholly owned subsidiary of Pfizer | Phase classification: P1/2 --> P2

P=N/A, N=26, Not yet recruiting, Beijing Anzhen Hospital, Capital Medical University; Beijing Anzhen Hospital, Capital Medical University

P2, N=20, Not yet recruiting, Zhejiang Cancer Hospital; Zhejiang Cancer Hospital

P2, N=20, Not yet recruiting, Fujian Medical University Union Hospital; Fujian Medical University Union Hospital

P=N/A, N=48, Recruiting, Qilu Hospital of Shandong University | Not yet recruiting --> Recruiting

P2, N=222, Recruiting, Sun Yat-sen University

Disitamab vedotin demonstrates promising anti-tumor effects in HER2-overexpressing mCRC, offering patients an additional treatment option.

P1, N=150, Recruiting, RemeGen Co., Ltd. | Not yet recruiting --> Recruiting

This is the first exploratory trial demonstrating substantial anti-tumor activity and a manageable safety profile using a HER2-targeting agent in patients with HER2-low mUC. This study was registered at ClinicalTrials.gov (ClinicalTrials.gov: NCT04073602).

P1, N=150, Not yet recruiting, RemeGen Co., Ltd.

The treatment of brain metastasis has been a topic of ongoing discussion. Our experience may offer valuable insights into managing HER2-positive progressive symptomatic brain metastases.

This case study suggests that the anti-Her-2 regimen involving Disitamab Vedotin and Pyrotinib may offer a potential salvage treatment option for patients with Her-2-amplified mCRC patients. However, further validation in larger cohorts is necessary in future studies.

P2, N=55, Active, not recruiting, Qilu Hospital of Shandong University | Trial completion date: Dec 2024 --> Dec 2025

P2, N=122, Active, not recruiting, Seagen Inc. | Recruiting --> Active, not recruiting

P3, N=400, Recruiting, Seagen Inc. | N=700 --> 400

This study confirms that cTURBT combined with RC48-ADC treatment for HER2-positive MIBC is superior to combined GC treatment in terms of RFS and OS, representing an effective treatment regimen for bladder preservation in MIBC patients.

P2, N=20, Recruiting, Fujian Medical University Union Hospital

P1/2, N=221, Recruiting, RemeGen Co., Ltd. | Trial primary completion date: Dec 2024 --> Dec 2025

DV was effective in treating breast and gastric cancer xenograft tumors resistant to T-DM1 and/or T-DXd. The combination of DV with T-DM1 or T-DXd demonstrated promising activity.

P=N/A, N=23, The Seventh Affiliated Hospital of Sun Yat-Sen University; The Seventh Affiliated Hospital of Sun Yat-Sen University

P=N/A, N=30, Recruiting, Chinese PLA General Hospital; Chinese PLA General Hospital

P2, N=30, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

P2, N=56, Recruiting, The First Affiliated Hospital of Wenzhou Medical University; The First Affiliated Hospital of Wenzhou Medical University

P1, N=76, Recruiting, The First Affiliated Hospital, Sun Yat-sen University; The First Affiliated Hospital, Sun Yat-sen University

No new safety risks were observed. In sum, the RC48 and anti-PD-1 IT combination showed good efficacy and a manageable safety profile, indicating its strong potential as an advanced GC therapeutic option.

P2, N=40, Recruiting, RemeGen Co., Ltd. | Not yet recruiting --> Recruiting | Initiation date: Nov 2024 --> Feb 2025

P2, N=55, Active, not recruiting, Qilu Hospital of Shandong University | Not yet recruiting --> Active, not recruiting

P2, N=110, Recruiting, Qilu Hospital of Shandong University | Not yet recruiting --> Recruiting

P2, N=110, Recruiting, Qilu Hospital of Shandong University | Not yet recruiting --> Recruiting

Her-2 overexpression can occur in late-stage EGFR-mutant lung adenocarcinoma after multiline treatment. RC48 can achieve sustained remission in these patients.

P1/2, N=221, Recruiting, RemeGen Co., Ltd. | Phase classification: P1 --> P1/2 | N=25 --> 221

P2, N=58, Recruiting, Shanghai Pulmonary Hospital, Shanghai, China

P2, N=36, Recruiting, Fudan University | Not yet recruiting --> Recruiting

P2, N=25, Recruiting, Guangdong Provincial People's Hospital

P2, N=110, Not yet recruiting, Qilu Hospital of Shandong University

This extensive study in China demonstrated that RC48 has excellent therapeutic potential for both HER2-positive and HER2-low MBC with a favorable safety profile. The study also suggests that combination therapy significantly boosts efficacy beyond monotherapy, indicating a promising avenue for future ADC development.

Studies evaluating ADCs (trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG), MRG002, and RC48-ADC) in patients with HER2-low a/mBC were included. Future studies should focus on bringing ADCs into earlier lines of therapy in this population. This study was registered in PROSPERO (CRD42024452962).

The combination of RC48 with platinum+/- bevacizumab resulted in the highest ORR of 71.4% (5 out of 7 patients), with HER2 TKI following at a 50.0% ORR (4 out of 8 patients). RC48, particularly in combination regimens, demonstrates promising efficacy in advanced NSCLC with HER2 alterations. These findings underscore the need for further research to validate RC48's application in clinical practice.

RC48-ADC showcases promising efficacy and manageable safety in patients with both HER2-positive and HER2-low-expression mBC.

P1/2, N=35, Not yet recruiting, Zhejiang Cancer Hospital; Zhejiang Cancer Hospital

From gemtuzumab ozogamicin to trastuzumab emtansine (T-DM1), and now to third-generation agents such as trastuzumab deruxtecan (DS-8201) and disitamab vedotin (RC48), improvements have been made in target selectivity, potency, linker stability, and reduced off-target effects. ADCs represent a promising frontier in precision cancer treatment, with continued research enhancing their potential in breast cancer and beyond. This review provides a comprehensive exploration of ADCs' evolution in breast cancer therapy, offering a molecular perspective to inform clinical practice and update colleagues on this dynamic field.