Clinical trial NCT04681911: Inetetamab Combined With Pyrotinib and Chemotherapy in the Treatment of HER2 Positive Metastatic Breast Cancer
Official title: A Phase II Single-arm Clinical Trial of Inetetamab Combined With Pyrotinib and Chemotherapy in the Treatment of HER2 Positive Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Breast Cancer
Keywords: HER2 positive metastatic breast cancer
Inetetamab
Pyrotinib
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2020-12-23
Enrollment: 71
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: In order to improve the curative effect and prolong the survival rate, we added Inetetamab to the current second-line treatment regimen of Pyrotinib combined with chemotherapy
Primary purpose: TREATMENT

Brief summary: HER2-targeted therapy after the failure of trastuzumab treatment has become a new difficulty and challenge. Inetetamab, a new antibody to optimize the ADCC effect, has become one of the second-line treatment options after trastuzumab fails, showing good survival benefits. Pyrotinib, another second-line HER2 targeted drug, is a typical representative of TKI drugs, which not only has a strong HER2 antagonistic effect but also can synergize with monoclonal antibodies to amplify the ADCC effect. Pyrotinib and Inetetamab showed excellent anti-tumor efficacy and good safety in TKI and optimized ADCC respectively. we plan to carry out a phase II single-arm clinical study to evaluate the efficacy and safety of "Inetetamab combined with Pyrotinib and chemotherapy" in the treatment of her positive metastatic breast cancer.

Detailed description: Trastuzumab is the first target drug for HER2 positive metastatic breast cancer, which can significantly improve the survival of patients with HER2 positive metastatic breast cancer and become the first-line standard treatment. However, the selection of second-line targeted drugs after the failure of trastuzumab treatment has become a new difficulty and challenge. Studies have shown that the ADCC effect is one of the main mechanisms of the anti-tumor effect of trastuzumab. Therefore, Inetetamab, a new antibody to optimize the ADCC effect, has become one of the second-line treatment options after trastuzumab fails, showing good survival benefits. Pyrotinib, another second-line HER2 targeted drug, is a typical representative of TKI drugs, which not only has a strong HER2 antagonistic effect but also can synergize with monoclonal antibodies to amplify the ADCC effect. As two important class 1.1 innovative drugs in China, Pyrotinib and Inetetamab showed excellent anti-tumor efficacy and good safety in TKI and optimized ADCC respectively. Considering that the current guidelines recommend the combination of multiple anti-HER2 targeted drugs, and basic research also shows that Pyrotinib and Inetetamab have a synergistic effect, we plan to carry out a phase II single-arm clinical study to evaluate the efficacy and safety of "Inetetamab combined with Pyrotinib and chemotherapy" in the treatment of her positive metastatic breast cancer, so as to provide better results for patients with HER2 positive metastatic breast cancer Treatment options!

Eligibility criteria: Inclusion Criteria:

Subjects must meet all of the following conditions:

1. Adult female patients (age 18-70 years) with metastatic breast cancer confirmed by pathology or imaging;
2. Pathological diagnosis of HER-2 was positive (definition: immunohistochemical results were + + + or in situ hybridization results were positive);
3. Received trastuzumab treatment in the past;
4. the patients have received 1-3 treatments for metastatic breast cancer in the past;
5. According to RECIST 1.1, patients with at least one target lesion or simple bone metastasis can be evaluated;
6. ECoG score of physical status was less than 2, and the expected survival time was not less than 3 months;
7. Prior treatment-related toxicity should be reduced to NCI CTCAE (version 5.0) ≤ 1 degree (except for hair loss or other toxicity which is considered as no risk to patient's safety according to the investigator's judgment) 8）LVEF≥50%；

9) Sufficient functional reserve of bone marrow

1. White blood cell count (WBC) ≥ 3.0 × 10 \^ 9 / L,
2. Neutrophil count (ANC) ≥ 1.5 × 10 \^ 9 / L,
3. Platelet count (PLT) ≥ 100 × 10 \^ 9 / L 10) Previous treatment-related toxicity should be relieved as NCI CTCAE (version 5.0) ≤ 1 degree, total bilirubin (TBIL) ≤ 1.5 × upper limit of normal value (ULN), alanine aminotransferase (ALT / AST) ≤ 2.5 × ULN (liver metastasis patients ≤ 5xuln), serum creatinine ≤ 1.5 × ULN or creatinine clearance rate (CCR) ≥ 60 ml / min; 11) Be able to understand the research process, volunteer to participate in the study, and sign informed consent.

Exclusion Criteria:

Subjects were not allowed to participate in the study if they had any of the following conditions:

1. No trastuzumab treatment was received;
2. Have received more than 3 therapeutic regimens for metastatic breast cancer;
3. No treatment for metastatic breast cancer was received;
4. Patients who are known to be allergic to active or other components of the study drug.
5. They received radiotherapy, chemotherapy, endocrine therapy within 4 weeks before enrollment, or were participating in any clinical trials of intervention drugs;
6. Pregnant or lactating women, women of childbearing age who refused to take effective contraceptive measures during the study period.
7. Any other situation in which the researcher considers that the patient is not suitable for the study may interfere with the concomitant diseases or conditions involved in the study, or there are any serious medical barriers that may affect the safety of the subjects (e.g., uncontrollable heart disease, hypertension, active or uncontrollable infection, active hepatitis B virus infection)

Primary outcomes:
measure: Objective Response Rate，ORR
timeFrame: 18 weeks after enrollment
Secondary outcomes:
measure: Progression Free Survival，PFS
timeFrame: 2 years
measure: overall survival，OS
timeFrame: 4 years
measure: Clinical Benefit Rate，CBR
timeFrame: 24 weeks after enrollment
measure: the rate of adverse events
timeFrame: up to 24 weeks after enrollment
measure: Quality of life scale score，QoL
timeFrame: 1 year
measure: Exploration of biomarkers
timeFrame: the first week after the enrollment
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat Sen Memorial Hospital，Sun Yat sen University
state: Guangdong
Study officials:
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Jianli Zhao
role: PRINCIPAL_INVESTIGATOR
References:
citation: Li X, Yang C, Wan H, Zhang G, Feng J, Zhang L, Chen X, Zhong D, Lou L, Tao W, Zhang L. Discovery and development of pyrotinib: A novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor with favorable safety profiles for the treatment of breast cancer. Eur J Pharm Sci. 2017 Dec 15;110:51-61. doi: 10.1016/j.ejps.2017.01.021. Epub 2017 Jan 21.
citation: Ma F, Ouyang Q, Li W, Jiang Z, Tong Z, Liu Y, Li H, Yu S, Feng J, Wang S, Hu X, Zou J, Zhu X, Xu B. Pyrotinib or Lapatinib Combined With Capecitabine in HER2-Positive Metastatic Breast Cancer With Prior Taxanes, Anthracyclines, and/or Trastuzumab: A Randomized, Phase II Study. J Clin Oncol. 2019 Oct 10;37(29):2610-2619. doi: 10.1200/JCO.19.00108. Epub 2019 Aug 20.
citation: Ma F, Li Q, Chen S, Zhu W, Fan Y, Wang J, Luo Y, Xing P, Lan B, Li M, Yi Z, Cai R, Yuan P, Zhang P, Li Q, Xu B. Phase I Study and Biomarker Analysis of Pyrotinib, a Novel Irreversible Pan-ErbB Receptor Tyrosine Kinase Inhibitor, in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer. J Clin Oncol. 2017 Sep 20;35(27):3105-3112. doi: 10.1200/JCO.2016.69.6179. Epub 2017 May 12.