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Trastuzumab

Letrozole

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Antineoplastic Agents, Immunological

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Hormone Antagonists

After providing written informed consent, the participants will undergo combined treatment of pyrotinib maleate, CDK4/6 inhibitor dalpiciclib, trastuzumab and letrozole. The effectiveness of the combined treatment will be evaluated by MRI every two treatment cycles. If the disease progresses, the participant will withdraw from the trial. If the combined treatment has identified effectiveness, the participant will undergo surgical treatment within 4 weeks (over 2 weeks) after termination of the neoadjuvant treatment. The patients will be followed up for 5 years.

Pyrotinib maleate, dalpiciclib, Trastuzumab, letrozole

Nan Niu, MD

Cai-Gang Liu, PHD

NOAH study confirmed that trastuzumab combined with chemotherapy can significantly improve PCR compared with chemotherapy alone, and established the status of trastuzumab as a new adjuvant targeted therapy. The emergence of CDK4/6 inhibitors has brought hope to breast cancer patients resistant to endocrine therapy. studies have shown that pyrotinib maleate combined with CDK4/6 inhibitor can significantly inhibit the proliferation of HER2 positive breast cancer cell lines, reduce the activation of pAKT and pHER3, inhibit cell arrest in G0-G1 phase, and increase cell apoptosis. In the mouse model, pyrotinib maleate combined with CDK4/6 inhibitor exhibits higher anti-tumor activity than any anti-tumor drug alone. Moreover, the toxicity of the combined therapy does not increase compared with monotherapy. This provides a good preclinical model for the treatment of breast cancer by pyrotinib maleate combined with CDK4/6 inhibitor.

In addition, NeoALTTO study、CALGB 40601 study、NSABP B-41 study confirmed that the clinical efficacy of lapatinib combined with trastuzumab combined chemotherapy was better than that of lapatinib or trastuzumab single target treatment group. Therefore, it is envisaged that the combination of pyrotinib maleate and dalpiciclib combined with letrozole on the basis of adding new trastuzumab to treat triple positive breast cancer will further improve the curative effect.

In conclusion, we believe that pyrotinib maleate combined with trastuzumab, dalpiciclib and letrozole can provide better strategies for neoadjuvant therapy in patients with II-III three positive breast cancer.

This multi-center, single-arm, open-label trial will include 12 patients with stage II-III triple-positive breast cancer. After providing written informed consent, the participants will undergo combined treatment of pyrotinib maleate, CDK4/6 inhibitor dalpiciclib, trastuzumab，and letrozole. The effectiveness of the combined treatment will be evaluated by MRI every two treatment cycles. If the disease progresses, the participant will withdraw from the trial. If the combined treatment has identified effectiveness, the participant will undergo surgical treatment within 4 weeks (over 2 weeks) after termination of the five treatment cycles.

Pyrotinib Maleate, Trastuzumab, SHR6390 and Letrozole in Combination for Stage II-III TPBC

Pyrotinib Maleate, Trastuzumab, SHR6390(Dalpiciclib) and Letrozole in Combination for Neoadjuvant Treatment of Stage II-III TPBC

Findings from this study will indicate whether pyrotinib maleate, CDK4/6 inhibitor SHR6390 and letrozole for treatment of stage II-III triple-positive breast cancer is safe and effective

tpCR is defined as the absence of residual invasive cancer on resected breast specimen and the sampled regional lymph nodes as shown by hematoxylin-eosin staining after completion of the neoadjuvant treatment

The proportion of patients who respond to the treatment at any study time point

There was no invasive carcinoma in the primary breast lesions (ypT0-is)

RCB score is obtained according to pathological evaluation after completion of neoadjuvant treatment and surgery

It refers to the length of time from the start of treatment to the death of the patient

It refers to the length of time from the start of medication after enrollment to the death of the patient because of the recurrence, distant metastasis of the disease, invasive contralateral breast cancer, or any other cause

Number of Adverse Events using NCI CTCAE 5.0

Shengjing Hospital

Professor

Immune System Diseases

Hypersensitivity

Fulvestrant

Tin Fluorides

Antineoplastic Agents, Hormonal

once a day, 125mg each time, taking for 3 weeks, stopping for 1 week, 4 weeks as a cycle. It is recommended to take medicine at about the same time every day, take it with warm water, and fast at least 1 hour before and after taking medicine

Pyrotinib Maleate

400mg once a day, oral administration within 30 minutes after breakfast, continuous administration for 28 days as a cycle

Dalpiciclib Isethionate Tablets

the initial dose is 8mg / kg and the subsequent dose is 6mg / kg. It is administered intravenously for 21 days.

Inetetamab

fluvestrant is administered intravenously on the 1/15 day of the first cycle, and then on the first day of each cycle, 500mg / time, intravenously

Min Yan

Min Yan, Professor

Based on different HR status, we explored the efficacy and safety of Pyrotinib and Dalpiciclib Isethionate Tablets based combination regimen in the first-line treatment of HER2 + MBC.

Cyclin D-CDK4/6-RB-E2F signaling pathway regulates the transformation of breast cancer cells from stage G1 to S, and plays an important role in the proliferation of breast cancer cells. HER2 protein regulates proliferation of breast cancer cells through PI3K/AKT signaling pathway. HER2 positive breast cancer patients need anti HER2 therapy. Data indicate that HER2 positive breast cancer patients often express cyclin D1 and E1, suggesting that anti HER2 therapy can synergy with CDK4/6 inhibitors.

A preclinical study shows that the combination of CDK4/6 inhibitor Dulcie and anti HER2 drug pyrrolidone can effectively reduce the phosphorylation of AKT and HER3, thereby promoting the apoptosis of HER2 positive breast cancer cells and achieving the purpose of inhibiting tumor.

In the clinical study of na-phere 2, piperacillin combined with trastuzumab, patuzumab and fluvestrant can significantly inhibit the expression of Ki67. MonarcHER study shows that the treatment of patients with advanced HR+HER2+ breast cancer after the failure of anti HER2+ is better than conventional chemotherapy plus anti HER2 therapy. The successful challenge of traditional chemotherapy is the opening of a new chapter in the treatment of HR+/HER2+. In 2021, ESMO 276P reported the interim data of darcilil combined with pyrroltinib in the first-line / second-line treatment of MBC. HR -, HER2 + MBC ORR can reach 81.8%, and the safety is controllable.

Based on different HR status, we explored the efficacy and safety of Pyrotinib and Dalpiciclib Isethionate Tablets based combination regimen in the first-line treatment of HER2 + MBC.

Treatment of Dalpiciclib Combined With Pyrotinib for Trastuzumab-sensitive HER2+ Advanced Breast Cancer(DAP-Her-02)

Treatment of Dalpiciclib Combined With Pyrotinib for Trastuzumab-sensitive HER2+ Advanced Breast Cancer: a Single Arm, Dual Cohort, Prospective, Open Phase II Exploratory Study

Individual participant data that underlie the results reported in this article, after de-identificationare available following article publication.

From the date into this study (signed ICF) to tumor progression or death.

The rate of CR and PR, determined using RECIST v1.1 criteria

Jiangsu HengRui Medicine Co., Ltd.

Henan Cancer Hospital

Chief Physician

All subjects enrolled will receive the following treatment：Pyrotinib±standard treatment.

Pyrotinib 400 mg/ D (once a day, at the same time each day) until the progression of disease; Chemotherapy regimens follow the programme cycle recommended by the guidelines or as determined by the investigator.

The dosage can be adjusted according to the protocol according to the adverse reactions of subjects. Subjects will continue to take medication until completion of the prescribed course of treatment, disease progression, toxicity intolerance, withdrawal of Informed Consent Form, or termination in the investigator's judgment.

Pyrotinib ± standard regimen Pyrotinib: 400 mg/day (once a day, orally at the same time every day), continued until disease progression;

standard regimen

li xiao, phd

li xiao

A single arm, open-label Phase II clinical study.The subjects were patients with lung, gastric and colorectal cancers.

Object: 1.The main purpose: T To observe and evaluate the efficacy of pyrotinib in patients with HER2-mutated/amplified metastatic solid tumors after failure of standard therapy; 2. Secondary objectives: To observe and evaluate the safety of pyrotinib in patients in HER2 mutated or amplified metastatic solid tumors after failure of standard treatment.

An Exploratory Basket Study of Pyrotinib Maleate Tablets in HER2 Mutated or Amplified of Metastatic Solid Tumors

Defined as proportion of complete response and partial response according to RECIST 1.1 criteria.

Defined as the time from the date of informed consent until to the date of death, regardless of the cause of death.

the proportion of patients whose tumors shrink or remain stable for a certain period of time, including complete remission (CR), partial remission (PR) and stable (SD) cases

Defined as the time from the date of informed consent to first documented disease progression (PD) using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) or death from any cause, whichever occurred first.

Zhongshan Hospital Xiamen University

Vinorelbine

Tubulin Modulators

Antimitotic Agents

Vinorelbine p.o. 40 mg once every other day

Chunfang Hao, PhD

This study is a single-center, single-arm, prospective phase II clinical study, which mainly evaluates the efficacy and safety of pyrotinib maleate combined with oral vinorelbine in the treatment of HER2-positive advanced breast cancer.

The most important treatment for HER2-positive breast cancer is based on anti-HER2 targeted therapy, combined with chemotherapy or endocrine therapy. China's original new anti-HER2 targeted therapy drug, pyrotinib, has obtained rapid approval from the country for its outstanding phase II clinical trial efficacy. In patients enrolled in the phase II trial, pyrotinib has a significant effect, but the combination of pyrotinib and capecitabine significantly increases the adverse reactions of diarrhea. For this reason, there is a lack of research on other combination schemes of pyrotinib in HER2 advanced breast cancer. In the first-line treatment, the combination therapy (HN) of trastuzumab and vinorelbine has shown that it also has a synergistic effect with vinorelbine in anti-HER2 targeted therapy. It provides a good evidence-based basis for the trial design of pyrotinib combined with vinorelbine soft capsules. This phase II clinical study is specially designed for preliminary exploration.

Pyrotinib Maleate Combined With Vinorelbine in the Treatment of HER2-positive Advanced Breast Cancer

A Prospective Phase Ⅱ Clinical Study of Pyrotinib Maleate Combined With Vinorelbine in the Treatment of HER2-positive Advanced Breast Cancer That Has Failed Trastuzumab Therapy

From enrollment to progression or death (for any reason)

From enrollment to death (for any reason)

Adverse events are described in terms of CTCAE 5.0

Tianjin Medical University Cancer Institute and Hospital

Antibodies

Antibodies, Monoclonal

Carboplatin

Docetaxel

Immunoglobulins

Pertuzumab

ARX788 1.5 mg/kg intravenously (IV) every three weeks plus pyrotinib maleate 320 mg orally once daily for 6 cycles

Trastuzumab (8 mg/kg first dose, followed 6 mg/kg) puls pertuzumab (840 mg first dose, followed 420 mg) plus docetaxel (75 mg/m3) plus carboplatin (AUC6) IV every 3 weeks for 6 cycles

ARX788

Pyrotinib maleate

Caigang Liu, MD

This is a randomized, open label Phase II-III neoadjuvant study comparing the efficacy and safety of ARX788 combined with pyrotinib maleate versus TCBHP (trastuzumab plus pertuzumab with docetaxel and carboplatin) in patients with HER2-positive breast cancer.

This is a randomized, open label Phase II-III neoadjuvant study comparing the efficacy and safety of ARX788 combined with pyrotinib maleate versus TCBHP (trastuzumab plus pertuzumab with docetaxel and carboplatin) in patients with HER2-positive breast cancer. Patients will be randomized (1:1) to one of the two treatment arms: arm 1, ARX788 plus pyrotinib maleate for 6 cycles; arm 2, trastuzumab plus pertuzumab with docetaxel and carboplatin for six cycles. Patients will undergo surgery after neoadjuvant therapy. Efficacy will be assessed every 2 cycles.

A Study of ARX788 Combined With Pyrotinib Maleate Versus TCBHP (Trastuzumab Plus Pertuzumab With Docetaxel and Carboplatin) as Neoadjuvant Treatment in HER2-positive Breast Cancer Patients

A Randomized, Open Label, Multi-center Phase II-III Neoadjuvant Study Comparing the Efficacy and Safety of ARX788 Combined With Pyrotinib Maleate Versus TCBHP (Trastuzumab Plus Pertuzumab With Docetaxel and Carboplatin) in Patients With HER2-positive Breast Cancer

The standard for removal of breast and lymph node tumors which means there are no infiltrating cancer cells at the primary breast and axillary lymph nodes, and only intraductal cancer is allowed on the breast.

The standard for breast and lymph node tumor removal which means that there are only infiltrating cancer cells at the primary breast tumor site.

Postoperative pathological results will be used to assess the residual tumor area of primary breast tumor (area in mm×mm), the cell density of the residual tumor（cell density in percentages）, the proportion of carcinoma in situ (proportion of carcinoma in percentages), the number of positive lymph nodes and the diameter of largest metastasis with residual nodes (diameter in mm). The RCB class can be estimated from the above five pathological parameters through a network calculation: RCB-0 in grades: pCR; RCB-I in grades: minimal residual tumor; RCB-II: moderate residual tumor; RCB-III in grades: extensive residual tumor.

The proportion of patients who achieve remission at any point during the study.

The time from the random date to death due to any cause.

The time from the day of enrollment to the first occurrence of recurrent disease, including second primary malignancies in the non-breast area and breast ductal carcinoma in situ.

Adverse events (AE) will be assessed as per the NCI-CTC AE 5.0 standard.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pyrotinib Maleate, Trastuzumab, SHR6390 and Letrozole in Combination for Stage II-III TPBC	NCT05228951	Breast Cancer	Pyrotinib malea...	18 Years - 75 Years	Shengjing Hospital
Treatment of Dalpiciclib Combined With Pyrotinib for Trastuzumab-sensitive HER2+ Advanced Breast Cancer(DAP-Her-02)	NCT05328440	Breast Neoplasm...	Pyrotinib Malea... Dalpiciclib Ise... Inetetamab Fulvestrant	18 Years -	Henan Cancer Hospital
An Exploratory Basket Study of Pyrotinib Maleate Tablets in HER2 Mutated or Amplified of Metastatic Solid Tumors	NCT05274191	Solid Tumor	Pyrotinib Malea... standard regime...	18 Years - 75 Years	Zhongshan Hospital Xiamen University
Treatment of Dalpiciclib Combined With Pyrotinib for Trastuzumab-sensitive HER2+ Advanced Breast Cancer(DAP-Her-02)	NCT05328440	Breast Neoplasm...	Pyrotinib Malea... Dalpiciclib Ise... Inetetamab Fulvestrant	18 Years -	Henan Cancer Hospital
Pyrotinib Maleate Combined With Vinorelbine in the Treatment of HER2-positive Advanced Breast Cancer	NCT04903652	HER2-positive A...	Pyrotinib Malea... Vinorelbine	18 Years - 75 Years	Tianjin Medical University Cancer Institute and Hospital
Treatment of Dalpiciclib Combined With Pyrotinib for Trastuzumab-sensitive HER2+ Advanced Breast Cancer(DAP-Her-02)	NCT05328440	Breast Neoplasm...	Pyrotinib Malea... Dalpiciclib Ise... Inetetamab Fulvestrant	18 Years -	Henan Cancer Hospital
A Study of ARX788 Combined With Pyrotinib Maleate Versus TCBHP (Trastuzumab Plus Pertuzumab With Docetaxel and Carboplatin) as Neoadjuvant Treatment in HER2-positive Breast Cancer Patients	NCT05426486	HER2-positive B...	ARX788 Pyrotinib malea... Trastuzumab Pertuzumab Docetaxel Carboplatin	18 Years - 75 Years	Shengjing Hospital
A Study of ARX788 Combined With Pyrotinib Maleate Versus TCBHP (Trastuzumab Plus Pertuzumab With Docetaxel and Carboplatin) as Neoadjuvant Treatment in HER2-positive Breast Cancer Patients	NCT05426486	HER2-positive B...	ARX788 Pyrotinib malea... Trastuzumab Pertuzumab Docetaxel Carboplatin	18 Years - 75 Years	Shengjing Hospital

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