317TiP - A randomized, multicenter, open-label phase II neoadjuvant study to evaluate the safety and efficacy of HER2-ADC disitamab vedotin in combination toripalimab or sequence chemotherapy in participants with HR-negative, HER2 low-expressing breast cancer

Background

Neoadjuvant chemotherapy or immunotherapy are usually recommended for hormone receptor–negative HER2 negative, defined as IHC 0,1+ or 2+ without HER2 gene amplification. Disitamab Vedotin(DV), a novel humanized anti-HER2 antibody conjugated with monomethyl auristatin E (MMAE) via a cleavable linker. Previous trials showed promising antitumor activity and an acceptable safety profile associated with DV alone or DV plus immunotherapy in patients with in HER2 low (IHC 1+, IHC 2+/FISH-) advanced or metastatic breast cancer. Immune checkpoint inhibition may enhance endogenous anticancer immunity after increased release of tumor-specific antigens with chemotherapy or ADC.

Trial design

This is a multicenter, open-label, randomized phase 2 trial. Patients aged 18 years or older with previously untreated stage II–III histologically documented HR-negative, HER2 Low were randomly assigned (1:1:1) to receive Arm1: DV 2.0mg/kg Q2W plus toripalimab 3.0mg/kg Q2W for 18 weeks, Arm2: Arm1 plus Carboplatin AUC 3 Q2W or AUC1.5 QW for 18 weeks, Arm3: DV 2.0mg/kg Q2W plus toripalimab 3.0mg/kg Q2W for 12 weeks followed by epirubicin 90mg/m² and cyclophosphamide 600 mg/m² Q3W plus toripalimab 3.0mg/kg Q2W for 12 weeks, which was then followed by surgery. Patients were stratified before randomization according to PD-L1 status (positive or negative), AJCC TNM staging (stage II to III). The primary endpoint is a pathological complete response, defined as pathological stage ypT0/Tis ypN0 at the time of definitive surgery. Secondary end points include event-free survival(EFS)/objective response rate (ORR)/ disease free survival (DFS)/overall survival (OS)/bpCR(ypT0/Tis) and the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0) was employed to assess the level of toxicity. This trial began in July 2023 and has enrolled 14 patients at the time of submission.

Clinical trial identification

NCT06227117.

Editorial acknowledgement

Legal entity responsible for the study

RemeGen Co., Ltd.

Funding

RemeGen Co., Ltd.

Disclosure

J. Fang: Financial Interests, Personal and Institutional, Leadership Role: Remegen Co., Ltd. All other authors have declared no conflicts of interest.