The Neoadjuvant Treatment of Early High-risk Triple Negative Breast Cancer With HRD Positive With Iparomlimab and Tuvonralimab Combined With Olaparib and Paclitaxel

NCT07187674 | Not Yet Recruiting

• 1 other identifier: IITGC-1645-0513
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

Breast cancer is one of the most common malignant tumors in women, accounting for the first cancer-related death cause in women. In recent years, the incidence has gradually increased, and the trend is younger. In 2022, the estimated number of new cases of female breast cancer worldwide is 2.389 million, and the estimated number of deaths is 666000. Triple negative breast cancer (TNBC) refers to breast cancer that is negative for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, accounting for about 10% - 20% of malignant breast tumors. . At present, chemotherapy is still the main means of clinical treatment of TNBC, but the heterogeneity of TNBC in molecular level, pathology and clinical characteristics leads to different sensitivity of patients to different chemotherapeutic drugs, especially the sensitivity of most elderly patients to chemotherapeutic drugs is not high, and the prognosis is poor. The development of immunotherapy in the field of breast cancer has witnessed the continuous deepening of medical understanding of cancer treatment. In the past, breast cancer was often regarded as a "cold tumor" insensitive to immunotherapy, but with the deepening of research, immunotherapy gradually occupied an important position in the treatment of breast cancer. The ongoing research hopes to identify patients who may benefit more from immunotherapy according to their respective tumor immune microenvironment. Its mechanism of action mainly includes two aspects: one is to restore the normal recognition and attack ability of the immune system to tumor cells and break the immune escape mechanism of tumor cells; The second is to stimulate a lasting immune response, so that the immune system can continuously monitor and clear tumor cells. Therefore, this study intends to evaluate the efficacy and safety of Iparomlimab and tuvonralimab combined with olaparib and paclitaxel in the neoadjuvant treatment of early high-risk TNBC with HRD positive. It is planned to enroll 20 subjects. After enrollment, the subjects will receive six cycles of combination therapy with olaparib and docetaxel. Take 3 weeks as a treatment cycle until the treatment termination event specified in the protocol occurs, and the subject will continue to conduct postoperative efficacy and safety visits after the end of treatment. After neoadjuvant treatment, according to the routine treatment process of breast cancer, the subject will receive breast cancer surgery; After surgical treatment, according to the residual breast lesions of the patient, the attending physician and the subject will agree on the subsequent treatment plan.

Conditions

Triple Negative Breast Cancer (TNBC)

Outcome Measures

Primary Outcomes (1)

• Total Pathological Complete Response (tpCR)

  No invasive cancer cells in breast and axilla（ypT0/is N0）

  5 months

Secondary Outcomes (5)

• Breast Pathological Complete Respons(bpCR)

  5 months

• Objective Response Rate(ORR)

  12 months

• 3-year Disease Free Survival

  40 months

• Ratio of Residual Cancer Burden (RCB) 0-1

  5 months

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  40 months

Other Outcomes (4)

• Exploratory endpoint：PD-L1 expression level

  5 months

• Exploratory endpoint：TILs level

  5 months

• Exploratory endpoint：Ki-67 index

  40 months

Study Arms (1)

Iparomlimab and tuvonralimab combined with olaparib and paclitaxel

EXPERIMENTAL

Drug: Iparomlimab and tuvonralimab combined with olaparib and paclitaxel

Interventions

Iparomlimab and tuvonralimab combined with olaparib and paclitaxel DRUG

The main objective of this study is to evaluate the tpCR of early high-risk TNBC with HRD positive treated with Iparomlimab and tuvonralimab combined with olaparib and paclitaxel as neoadjuvant therapy

Iparomlimab and tuvonralimab combined with olaparib and paclitaxel

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily join this study and sign an informed consent form;
• Women aged ≥ 18 years and ≤ 70 years with early breast cancer:According to the definition of the latest ASCO/CAP guidelines, triple negative breast cancer patients with T1cN1-2 or T2-4N0-2 stage confirmed by histopathology;
• Subjects with HRD positive tumor tissue evaluation;
• According to RECIST 1.1, there must be at least one measurable lesion;
• ECOG score: 0 to 1;
• Tumor tissue specimens that can be used for biomarker detection;
• The function of important organs meets the following requirements (no blood components or cell growth factor drugs are allowed to be used within 14 days before the first medication):
• Absolute neutrophil count ≥ 1.5 × 10\^9/L; Platelets ≥ 100 × 10\^9/L; Hemoglobin ≥ 90 g/L; Serum albumin ≥ 30 g/L; Thyroid stimulating hormone (TSH) ≤ 1 × ULN (if abnormal, FT3 and FT4 levels should be examined simultaneously. If FT3 and FT4 levels are normal, they can be included in the group); Serum total bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 2.5 × ULN; AKP≤ 2.5×ULN； Serum creatinine ≤ 1.5 × ULN;
• Female patients with non-surgical sterilization or childbearing age need to use a medically approved contraceptive measure (such as intrauterine device, contraceptive pill or condom) during the study treatment period and within 3 months after the end of the study treatment period; ; And must be non lactation; For male patients whose partners are women of childbearing age, effective methods of contraception should be used during the trial and within 3 months after the last administration of trial drugs.

You may not qualify if:

• There is any active autoimmune disease or history of autoimmune disease (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism; patients with vitiligo or asthma in childhood have been completely relieved and do not need any intervention after adulthood can be included; asthma requiring medical intervention with bronchodilators cannot be included);
• Currently using immunosuppressants or systemic hormone therapy for immunosuppression (with a dosage of \>10mg/day of prednisone or other equally effective hormones), and still continuing to use them within 2 weeks prior to enrollment;
• Severe allergic reaction to other monoclonal antibodies;
• Known history or evidence of interstitial lung disease or active non infectious pneumonia;
• Having other malignant tumors in the past 5 years or at the same time (except for cured skin basal cell carcinoma and cervical carcinoma in situ);
• Have hypertension and can not be well controlled after antihypertensive drug treatment; Had hypertension crisis or hypertensive encephalopathy in the past;
• There are cardiac clinical symptoms or diseases that are not well controlled, such as: (1) heart failure above NYHA grade 2 (2) unstable angina pectoris (3) myocardial infarction within 1 year (4) clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention (5) qtc\>450ms (male); Qtc\>470ms (female);
• The urine routine showed that the urine protein was ≥ + +, and the 24-hour urine protein volume was confirmed to be \>1.0 g;
• Patients with active infection, unexplained fever ≥ 38.5 ℃ within 7 days before medication, or white blood cell count \>15 × 10\^9/l at baseline;
• Have congenital or acquired immune deficiency (such as HIV infected persons); Hepatitis B surface antigen (HBsAg) positive and hepatitis B virus deoxyribonucleic acid (HBV DNA) ≥ 2000 iu/ml, or hepatitis C virus antibody positive;
• Less than 4 weeks before the study medication or may be vaccinated with live vaccines during the study period;
• Bilateral breast cancer;
• According to the judgment of the investigator, the patient has other factors that may affect the results of the study or cause the forced termination of the study, such as alcohol abuse, drug abuse, other serious diseases (including mental illness) requiring combined treatment, serious laboratory abnormalities, accompanied by family or social factors, which will affect the safety of the patient.

Sponsors & Collaborators

• Harbin Medical University: lead

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

olaparib; Paclitaxel

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Central Study Contacts

Jin song Wang S Wang

CONTACT

0451-86298091; taowangto2001@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician

Study Record Dates

• First Submitted: September 10, 2025
• First Posted: September 23, 2025
• Study Start: December 30, 2025
• Primary Completion (Estimated): June 15, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: September 23, 2025

Record last verified: 2025-09