2022ESMOBC 丨 Professor Yin Yongmei: New Drug, New Hope-Her3-DXD first expanded, look forward to more data announcement

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2022ESMOBC 丨 Professor Yin Yongmei: New Drug, New Hope-Her3-DXD first expanded, look forward to more data announcement

2022-05-15 06:13:06 8 ℃

Editor's note: HER3-DXD is a new type of HER3 targeted ADC drug, which used to show good anti-tumor activity and acceptable safety in related research on breast cancer. At the ESMO BC conference in 2022, HER3-DXD related studies were published one after another. "Tumor Watching" invited Professor Yin Yongmei of Jiangsu Provincial People's Hospital to summarize and comment on related research.

LBA3 —— Solti Tot-Her3 Opportunity Window Test: Patritumab Deruxtecan (HER3-DXD) The final result of early HR+/HER2-breast cancer in the treatment of early HR+/HER2-

Research background: Patritumab deruxTecan (Her3-DXD; U3-1402) is a new type of HER3 targeted ADC drug. Its antibody part is Patritumab. HER2/HER3 heterologous diode formation. HER3-DXD's carrier part is consistent with T-DXD and DATO-DXD. It is formed by Patritumab and topological agent Ⅰ inhibitors through covalent.

HER3-DXD shows good anti-tumor activity and acceptable safety in patients with a large pre-processing level of metastatic breast cancer.

Research method: Multi-centered pre-operational window test includes unprecedented HR+/HER2-surgical (≥1cm) breast cancer patients. Patients are classified according to the level before the treatment (pre-) ERBB3 mRNA level, and a single dose HER3-DXD (6.4 mg/kg) is given. The main ending is to evaluate the difference in Celtil scoring between the before and after the medication (the 21st day of the cycle 1, C1D21) samples (the change of the Celtil score is related to the clinical, protein group, and genome variables). Bad events (AES) presses CTCAE V5.0 grades.

The endpoint of secondary research includes: the objective relief rate (ORR) of clinical evaluation at C1D21; CELTIL scores that change according to the baseline ERBB3 mRNA and HER3 IHC basic protein expression level; Change; security and tolerance.

Research results: Generally speaking, 77 of the 78 patients who entered the group reached the main ending of the evaluation.

Base line characteristics: The average age of patients is 53, and the size of the median tumor is 21mm; CN0 is 71%; the average KI67 level is 27%.

According to the ERBB3 MRNA level before treatment, the tumor is divided into four groups: high (n = 21), medium (n = 21), low (n = 21), and ultra -low (n = 14). All patients' PAM50 subtypes are identified: type A (Lum) type A accounted for 52%, Luminalb types account for 41%, HER2 excessive expression accounts for 3%, and BASAL-LKE accounts for 4%.

The orr of the patient in the study was 45%. Celtil increased significantly at C1D21 (average differences+6.8, P <0.001), but this increase is only observed in patients with relief (P <0.001) that there is no in patients with stable illness (P = 0.135). See.

Non -luminal subtype and high recurrence risk scores are related to the high response of Celtil. Before the treatment, the level of ERBB3 mRNA has nothing to do with the changes or clinical response of Celtil. The pairing of KI67 after treatment is significantly reduced (P <0.001), while the ERBB3 mRNA has not significantly reduced (P = 0.13). At C1D21, the patient's immune gene was induced and the proliferation gene was suppressed (false discovery rate = 5%). Celtil scores independent of the baseline ERBB3 mRNA and HER3 immunization group levels.

In terms of security, 74 (95%) patients reported any level of AES. The most common level 3-4 AES is: decrease in neutral granulocytes (n = 6), elevation of ALT (n = 2), and diarrhea (n = 1).

Research conclusions: In patients with unb treatment early HR+/HER2-breast cancer, the treatment of single dose HER3-DXD will cause clinical significance reactions, adding immune infiltration and inhibitory proliferation in ERBB3 mRNA at different baseline levels. Safety is consistent with previous reports.

204-TIP: Her3-DXD in Phase II Studies in patients with metastatic breast cancer

Research background: HER3 is a member of HER receptor tyrosine kinase (RTK) family, which is expressed in many physical tumors including breast cancer. This over -expression is related to the decline in survival. HER3 lacks an internal kinase activity, forming an alien gathery with other RTK (especially HER2), and the subsequent downstream signal pathway promotes the occurrence and metastasis of the tumor.

Research design: The study will be included in HER2-breast cancer patients who have advanced in 120 or local progress, and divided them into two parts (A, B). Patients with admission are ≥18 years old, and there are measured tumors according to the RECIST V1.1 standard. The ECOG PS is 0-1. Patients with three-negative breast cancer are allowed to accept 1-3 chemotherapy. Patients with hormone receptor (HR+) have previously accepted endocrine therapy (ET)+CDK4/6 inhibitors, which are not limited to previous ET drugs; and all patients only allow previous chemotherapy of 0-2. If patients have used anti -HER3 targeted drugs in the past, they are excluded. The main goal is to evaluate the objective relief rate (ORR) and the 6 -month unsuccessful survival period (PFS). Secondary goals include: the safety and tolerance of HER3-DXD in patients with MBC; the reaction duration (DOR) and PFS of MBC patients.

CT scans are performed every 6 weeks for 6 months, and then every 9 weeks. Part A will recruit 60 patients. They will conduct pathological examinations before treatment to determine whether the expression of specific biomarkers (ER/PR/HER2/HER3) shows better preliminary effects after 24 weeks (related blood and blood and blood and Biopsy is necessary during treatment)

Part B will be included in 60 patients (up to 20 patients in 3 sub -groups), which will be defined according to the biomarker expression mode and preliminary efficacy results according to the biomarkers of part A. Patients from the same biomarkers of the same biomarkers in parts A and B will be combined for final efficacy analysis.

Expert Reviews

Her protein is a recipient tyrosine kinase family, which plays a role in normal and tumor cell biology. The family includes four high -level members: EGFR (ERBB1/HER1), HER2 (ERBB2), HER3 (ERBB3) and Her4 (ERBB4). HER3 is an important member of the HER protein family. Because of the lack of tyrosine kinase activity in its intracellular domain, it has not attracted people's attention. With the in -depth understanding of it in recent years, some targeted drugs have also been developed, and clinical trials related to these drugs are also carried out one after another.

In the treatment of patients with breast cancer, the emergence of new drugs represents more hopeful treatment, and it may also bring more treatment options to clinicians. We encourage more clinical trials and look forward to HER3-DXD related related As a result, it can be applied earlier to the clinic and benefit more patients.

Expert Introduction

Professor Yin Yongmei

Professor, chief physician, doctoral supervisor in Nanjing Medical University First Affiliated Hospital

Deputy Dean of Jiangsu Maternal and Child Health Hospital (Maternal and Children's Branch of the People's Hospital of Jiangsu Province)

Vice Chairman of the China Clinical Oncology Society

Vice Chairman of Beijing Hisco Clinical Oncology Research Foundation

Deputy Chairman of the China Clinical Oncology Society of Breast Cancer Expert Committee

Executive Member of the Breast Cancer Professional Committee of the China Anti -Cancer Association

The chairman of the Education Expert Committee of the China Clinical Oncology Society

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