Inetetamab Combined With Pyrotinib and Chemotherapy in the Treatment of HER2 Positive Metastatic Breast Cancer

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04681911
• Other study ID #: 2020-KY-125
• Status: Recruiting
• Phase: Phase 2
• Start date: September 9, 2020
• Est. completion date: September 9, 2024

Study information

• Verified date: December 2020
• Source: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Contact: Jianli Zhao
• Phone: 86-20-34070870
• Email: zhaojli5[@]mail.sysu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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!

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 71
• Est. completion date: September 9, 2024
• Est. primary completion date: September 9, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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)

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Inetetamab
Inetetamab: 8mg/kg for the first dose, 6mg/kg for the following doses, every 3 weeks for one cycle.
• Pyrotinib
Pyrotinib: 400mg, oral, every day.
• Capecitabine
Capecitabine, 1000 mg/m2, d1-d14, 3-week cycle
• Gemcitabine
Gemcitabine, 1000 mg/m2, D1, D8, 3-week cycle
• Vinorelbine
Vinorelbine, 25-30 mg/m2, D1, D8, 3-week cycle
• Carboplatin
Carboplatin, AUC = 6, 3-week cycle
• Albumin paclitaxel
Albumin paclitaxel, 100 mg/m2, weekly
• Eribulin
Eribulin, 1.4 mg/m2, D1, D8, 3-week cycle

Locations

Country	Name	City	State
China	Sun Yat Sen Memorial Hospital,Sun Yat sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Country where clinical trial is conducted

China, 

References & Publications (3)

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. — View 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 Epi — View 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 Rando — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate,ORR	Objective response rate assessed at 18 weeks after enrollment,that is about 6 cycles of treatment	18 weeks after enrollment
Secondary	Progression Free Survival,PFS	The time from the beginning of treatment to the progression or death of the patient	2 years
Secondary	overall survival,OS	The time from the beginning of treatment to the death of the patient	4 years
Secondary	Clinical Benefit Rate,CBR	Clinical Benefit Rate assessed at 24 weeks after enrollment,that is about 8 cycles of treatment	24 weeks after enrollment
Secondary	the rate of adverse events	The probability and severity of adverse reactions were analyzed up to 24 weeks after enrollment	up to 24 weeks after enrollment
Secondary	Quality of life scale score,QoL	The quality of life score of patients during treatment was analyzed(FACT-B). Performance Status Rating (PSR) was demonstrated for the FACT-B total score, which is the result of the following subscale scores: SWB (the Social / family Well-Being subscale) , EWB (the Emotional Well-Being subscale), AC (Additional Concerns subscale), PWB (the Physical Well-Being subscale), FWB (the Functional Well-Being subscale)	1 year
Secondary	Exploration of biomarkers	Objective to explore the correlation between biomarkers and the ORR. The biomarkers will be test by nest-generation sequence, which include 520 genes and tumor mutation burden, like ERBB2/TP53/PIK3CA/ERBB4/CCND1 and so on.	the first week after the enrollment