The purpose of this study is to evaluate the efficacy and safety of Disitamab Vedotin in combination with Pertuzumab with or without Toripalimab neoadjuvant therapy in patients with HER2-positive breast cancer.
This is an open-label, randomized, multicenter, Phase II Study designed to evaluate safety and efficacy of Disitamab Vedotin in combination with Pertuzumab with or without Toripalimab neoadjuvant therapy inr patients with HER2-positive breast cancer. The primary objectives of the study are to explore combination neoadjuvant therapy in participants with previously untreated HER2-positive breast cancer, by assessment of pCR .
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
2.0mg/kg, intravenous infusion,D1, every 2 weeks, Every 6 weeks is a treatment cycle. A total of 3 cycles (18 weeks) of treatment are performed.
Initial dose 840mg, after 2nd dose 420mg intravenous infusion, every 3 weeks
3.0 mg/kg, intravenous infusion, D1, every 2 weeks
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, China
RECRUITINGPathological complete response (pCR) rate (ypT0/is ypN0)
Pathological complete response rate after neoadjuvant ( both breast and axillary lymph nodes, in which the breast may have residual carcinoma in situ);
Time frame: 1 month after surgery
Objective remission rate (ORR)
Objective response rate.ORR assessed according to the evaluation criteria for the efficacy of solid tumors (RECIST 1.1)
Time frame: Up to approximately 2 years
Disease free survival(DFS)
From the date of surgery to the first local, regional, contralateral or distant recurrence, and death from any cause including 3- and 5-year event-free survival
Time frame: Up to approximately 5 years
Event free survival (EFS)
The time from random assignment to disease progression, including local progression before surgery; disease recurrence-local, regional, distant, ipsilateral noninvasive, or contralateral (invasive or noninvasive)-or death from any cause;
Time frame: Up to approximately 5 years
Overall survival (OS)
OS is defined as the time from the date of randomisation until the date of death due to any cause.
Time frame: Date of randomization to date of death due to any cause, up to 5 years after the last subject randomized
Adverse events
To evaluate safety including adverse event rate and adverse event grade
Time frame: Up to approximately 2 months after surgery
Change in cluster of differentiation 8 (CD8)
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CD8 in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining.
Time frame: At baseline to surgery
Health-related quality of life - EORTC-QLQ-C30
Change from baseline in the physical functioning subscale of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scores. Scale scores range from 0-100. For functioning and global health status/ QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden
Time frame: Up to approximately 2 years
Residual cancer burden score
According to the extent of the residual cancer in the primary breast cancer site (mm\*mm), the residual cancer (mm\*mm), cell density of residual cancer (%), proportion of carcinoma in situ (%), number of positive lymph nodes and maximum diameter of lymph node metastasis (mm), the RCB index and corresponding RCB classification can be obtained. The RCB index and the corresponding RCB grade can be obtained based on the maximum diameter of the cancer (mm).
Time frame: 1 month after surgery
Change in tumor-infiltrating lymphocytes (TILs)
Defined as infiltrating lymphocytes isolated from tumor tissue.TILs in tumor samples by biopsy right before the first neoadjuvant therapy (baseline) and by surgery immediately after surgery would be evaluated by HE or immune staining。
Time frame: At baseline to surgery
Change in programmed cell death protein L1 (PD-L1)
PD1 in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining.
Time frame: At baseline to surgery