Disitamab Vedotin Plus Toripalimab Is Beneficial, Well-Tolerated in HER2+ MIBC

RC48-ADC, or disitamab vedotin (DV), is a novel anti-HER2 antibody-drug conjugate. DV combined with toripalimab, an anti–PD-1 monoclonal antibody, showed beneficial antitumor activity in patients with metastatic urothelial carcinoma in data presented at the 2024 American Society of Clinical Oncology Annual Meeting.

Xinan Sheng, MD, presented the preliminary efficacy and safety results of a prospective multicenter, phase 2 trial that examined the combination as a neoadjuvant therapy for patients with muscle invasive bladder cancer (MIBC) with HER2 expression.

The primary end point of the study is pathological clinical response (pCR) rate, while secondary end points include pathologic response rate, safety, and tolerability. A total of 44 patients with previously untreated MIBC were enrolled in the study. HER2 expression was required to be immunochemistry (IHC) ≥1+ tested locally.

Each patient received DV 2 mg/kg with toripalimab 3 mg/kg every 2 weeks for 6 cycles, followed by radical cystectomy (RC) and pelvic lymph node dissection (PLND) with curative intent within 4 weeks.

Clinical stages of the patient group at diagnosis included cT2N0 (38.6%), cT3N0 (29.5%), cT4aN0 (13.6%), and cT2-4aN1 (18.2%). HER2 expression of IHC 1+, 2+, or 3+ was 11.4%, 56.8%, and 31.8%, respectively.

At the data cutoff date in February 2024, 29 (65.9%) patients had completed RC plus PLND, with a pCR rate of 62.1% (18/29). The pathologic response rate was 75.9% (22/29).

Common treatment-related adverse events (TRAEs) were mostly grade 1 or 2 and included alopecia (36.4%), increase in alanine aminotransferase (31.8%), increase in aspartate aminotransferase (25.0%), rash (22.7%), increase in gamma-glutamyl transferase (22.7%), peripheral sensory neuropathy (22.7%), and asthenia (20.5%).

Grade 3-4 TRAEs occurred in 15.9% of patients. No deaths occurred, and no surgery was cancelled due to TRAEs.

The use of DV with toripalimab as a neoadjuvant treatment shows promising efficacy results for patients with MIBC with HER2 expression. Further investigation into this treatment combination for this patient population is warranted.