Neoadjuvant Therapy for Early Triple-Negative Breast Cancer: A Response-Guided Approach Using Iparomlimab and Tuvonralimab Injection in Combination With Chemotherapy

Iparomlimab and Tuvonralimab Injection (QL1706) is a bifunctional combination antibody targeting both programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4). This is a prospective clinical study that plans to enroll screened, eligible early-stage breast-cancer patients to receive neoadjuvant QL1706 plus chemotherapy (four cycles of TP ± four cycles of AC). After the four TP cycles, imaging and core biopsy will be performed. Patients who achieve radiologic complete response will proceed directly to surgery; those who do not will receive four additional AC cycles before surgery. A key feature is the incorporation of an response-guided neoadjuvant therapy（RGN）model to identify sensitive patients who can forgo anthracyclines, thereby reducing long-term cardiotoxicity.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer; Neoadjuvant Therapy; Immune Checkpoint Inhibitors; QL1706
• Intervention / Treatment: Drug: QL1706 combined with Chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yongsheng Jia, Doctor; Phone Number: +86 18622199359; Email: yongshengjia@tjmuch.com
• Study Contact Backup: Name: Wenxiao Liu; Phone Number: +86 18515456035; Email: liuwenxiao2016@outlook.com

Study Locations

• China
  • Tianjin, China
    • Tianjin Medical University Cancer Institute & Hospital
    • Contact: Yongsheng Jia, Doctor; Phone Number: +86 18622199359; Email: yongshengjia@tjmuch.com
    • Contact: Jun Zhang, doctor; Email: doctorjunzhang@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Voluntarily join this study, sign the informed consent form, and demonstrate good compliance;
• Age: 18-75 years old (at the time of signing the informed consent form);
• ECOG PS score: 0-1; expected survival time exceeding 6 months;
• Patients with primary breast cancer confirmed by histopathological or cytological examination;
• Primary tumor diameter > 2 cm as measured by local standard assessment methods;
• Judged by the investigator to meet the American Joint Committee on Cancer (AJCC) 8th edition breast cancer TNM staging criteria as cT2-cT4, cN0-cN3, cM0, with locally advanced or early-stage, unilateral, and histologically confirmed invasive breast cancer;
• Histopathologically confirmed early-stage triple-negative invasive breast cancer as defined by the latest ASCO/CAP guidelines;
• At least one measurable lesion according to RECIST 1.1;
• The patient agrees to undergo breast cancer resection surgery when meeting the surgical criteria after neoadjuvant therapy;
• PD-L1 expression status is known;
• Major organ functions are in good condition;
• Female subjects of childbearing potential must have a negative serum pregnancy test within 3 days prior to the first dose. If a female subject of childbearing potential engages in sexual activity with a non-sterilized male partner, the subject must use acceptable and effective contraception from screening onward and agree to continue these precautions until 12 months after the last dose of the study drug; periodic abstinence and rhythm methods are not acceptable contraceptive methods.

Exclusion Criteria:

• Patients with stage IV metastatic breast cancer or other patients deemed by the investigator as unable to achieve curative surgical resection through neoadjuvant therapy;
• Patients with inflammatory breast cancer;
• Patients who have had or currently have other malignancies within the past 3 years. The following two conditions may be eligible: other malignancies treated with a single surgical procedure, achieving continuous 5-year disease-free survival (DFS); cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor invading the basement membrane)];
• Breast cancer patients who have received antitumor therapies such as chemotherapy, endocrine therapy, or immune checkpoint inhibitors within the past 3 years, or who have undergone breast surgery (except diagnostic biopsy for primary breast cancer);
• Patients who have undergone major surgical treatment, incisional biopsy, or significant traumatic injury within 28 days prior to the start of study treatment (except diagnostic biopsy for primary breast cancer);
• Presence of any active autoimmune disease or a history of autoimmune disease;
• Patients currently using immunosuppressants or systemic hormonal therapy for immunosuppressive purposes (at a dose >10 mg/day prednisone or equivalent steroids) and continuing such treatment within 2 weeks prior to enrollment;
• Allergy to any study drug or any component or excipient of the drug;
• Patients with concomitant diseases judged by the investigator as seriously endangering the subject's safety or affecting study completion, or those deemed unsuitable for enrollment for other reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: QL1706 Combination Therapy; neoadjuvant QL1706 plus chemotherapy (four cycles of TP ± four cycles of AC).

Drug: QL1706 combined with Chemotherapy; Participants receive QL1706 every 3 weeks (Q3W) + Albumin-bound paclitaxel every 3 weeks (Q3W) + Cisplatin (Q3W) x 4 cycles. After the four TP cycles, imaging and core biopsy will be performed. Patients who achieve radiologic complete response will proceed directly to surgery; those who do not will receive QL1706 Q3W + epirubicin Q3W + cyclophosphamide Q3W x 4 cycles as neoadjuvant therapy before surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
tpCR（ypT0/is ypN0）	Up to approximately 27-30 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Radiologic complete response rate (iCR)	Up to approximately 27-30 weeks
epirubicin-cyclophosphamide regimen utilization rate	Up to approximately 16 weeks
Event-free Survival (EFS) as assessed by Investigator	Up to approximately 8 years
Percentage of participants who experience an adverse event (AE)	Up to approximately 60 weeks
Overall survival (OS)	Up to approximately 8 years
Health-Related Quality of Life (HR-QoL) score	Up to approximately 27-30 weeks

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital
• Investigators: Study Chair: Yongsheng Jia, Tianjin Medical University Cancer Institute and Hospital; Principal Investigator: Jun Zhang, Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 5, 2026
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2029

Study Registration Dates

• First Submitted: January 19, 2026
• First Submitted That Met QC Criteria: January 19, 2026
• First Posted (Actual): January 28, 2026

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 19, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Therapeutics; Drug Therapy
• Other Study ID Numbers: E20251311

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No