Efficacy and Safety of Extended-Dose Interval Immunotherapy Versus Standard-Dose Interval Immunotherapy for Advanced Triple-Negative Breast Cancer

NCT07401537 | Recruiting Phase 2

• 1 other identifier: SYSKY-2025-962-02
• Study Type: interventional
• Target: 416
• Locations: 1 country
• Sites: 1

Brief Summary

Triple-negative breast cancer (TNBC), defined by the lack of ER, PR and HER2 expression, is refractory to endocrine therapy and anti-HER2 agents. Chemotherapy was once the mainstay for advanced TNBC, but its limited efficacy necessitates optimized therapeutic strategies. TNBC's high TIL infiltration and elevated PD-L1 expression confer sensitivity to immune checkpoint inhibitors (ICIs), with ICI-chemotherapy combinations initially establishing first-line standard status. Emerging clinical evidence shows that ICI-antibody-drug conjugate (ADC) combinations outperform ICI-chemotherapy regimens, yet immune-related adverse events (irAEs) remain a critical clinical challenge. Expert consensus recommends continuing ICI therapy in advanced TNBC patients achieving CR, PR or SD after ICI-based combination therapy until disease progression or intolerable toxicity. Mechanistically, once ICIs reach target receptor saturation, dose escalation or high-frequency administration fails to boost efficacy but raises toxicity risk. Thus the investigators hypothesize that an ICI maintenance strategy with fixed dose and extended intervals can preserve efficacy, reduce toxicity, improve patient compliance, enhance quality of life and alleviate economic burden for advanced TNBC patients with CR/PR/SD after ICI-chemotherapy or ICI-ADC treatment.

Conditions

Triple -Negative Breast Cancer; Breast Cancer

Keywords

Immune-checkpoint inhibitors; Dose Interval

Outcome Measures

Primary Outcomes (1)

• mPFS

  Refers to the time from randomization date to the first observation of disease progression (based on RECIST v1.1 criteria) or death from any cause, whichever occurs first.

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years.

Secondary Outcomes (10)

• mOS

  From date of randomization until the date of death from any cause, assessed up to 3 years.

• DoR

  From date of achieving CR or PR until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years.

• DDC

  From date of achieving CR, PR, or SD until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years.

• Assessment of quality of life via the EORTC QLQ-C30 questionnaire.

  3 years.

• Assessment of quality of life via the EORTC QLQ-BR42 questionnaire.

  3 years.

Other Outcomes (1)

• Biomarker

  3 years (before and after therapy).

Study Arms (2)

Extended-Dose Interval

EXPERIMENTAL

During the maintenance therapy phase, the dose of PD-1 inhibitors is consistent with that of the standard therapy phase, administered every 6 weeks (q6w); the dose of chemotherapy or TROP2-ADC drugs is consistent with that of the standard therapy phase, administered every 3 weeks (q3w).

Drug: Extended-Dose Interval Immunotherapy

Standard-Dose Interval

ACTIVE COMPARATOR

During the maintenance therapy phase, the dosages of PD-1 inhibitors, chemotherapy, or TROP2-ADC drugs are maintained at the same levels as those in the standard treatment phase, administered every 3 weeks (q3w).

Drug: Standard-Dose Interval Immunotherapy

Interventions

Extended-Dose Interval Immunotherapy DRUG

During the maintenance therapy phase, the dose of PD-1 inhibitors is maintained at the same level as in the standard treatment phase, with the dosing interval extended to every 6 weeks (q6w).

Extended-Dose Interval

Standard-Dose Interval Immunotherapy DRUG

During the maintenance therapy phase, the dosage and dosing interval of PD-1 inhibitors are consistent with those in the standard therapy phase, administered every 3 weeks (q3w).

Standard-Dose Interval

Eligibility Criteria

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

You may qualify if:

• Voluntary consent to participate in this study and signing of the informed consent form.
• The age of the signatory of the informed consent form should be ≥18 years old and ≤70 years old.
• Advanced (locally recurrent inoperable or metastatic) TNBC confirmed by histology or cytology, defined as ER-negative, PR-negative, and HER2-negative.
• PD-L1 IHC detection in tumor tissue with a CPS score ≥1.
• Have received first-line standard immunotherapy combined with chemotherapy or immunotherapy combined with ADC and completed 6 cycles, with the last dose administered no more than 28 days before randomization.
• The therapeutic efficacy was confirmed as CR, PR or SD after 6-cycle standard treatment according to the RECIST v1.1 criteria.
• Plan to continue receiving immunotherapy.
• An Eastern Cooperative Oncology Group performance-status score of 0 or 1.
• The expected survival period exceeds 12 weeks.
• Adequate organ function:.
• No mental or intellectual abnormalities.
• Willing and able to comply with the trial protocol during the trial period.
• Female subjects of childbearing potential must agree to use highly effective contraceptive measures starting at least 7 days before the first dose and continuing until 24 weeks after the last dose. The serum pregnancy test result must be negative within 7 days prior to the first dose.

You may not qualify if:

• Untreated active brain metastases or meningeal metastases.
• Concomitant other malignant tumors with progression within the recent 5 years or requiring active treatment (excluding adequately treated and controlled carcinoma in situ and non-melanoma skin cancer).
• Concomitant severe non-malignant diseases that would affect the patient's compliance or put the patient at risk.
• Concomitant active infection.
• Receiving other anti-tumor therapies or participating in other interventional clinical trials.
• Inflammatory breast cancer.
• Dementia, intellectual disability, or any mental disorders that hinder the understanding of the informed consent form.
• History of allergic reactions to any components of the study drugs or existing contraindications to their use.
• Presence of any active autoimmune diseases or history of autoimmune diseases.
• Presence of poorly controlled clinical cardiac symptoms or diseases, such as:1) Heart failure of NYHA class II or above;2) Unstable angina pectoris;3) Myocardial infarction occurring within 1 year;4) Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention.
• Presence of grade ≥3 toxicities related to prior treatments that restrict the continuation of maintenance therapy.
• History of immunodeficiency, including HIV positivity, active HBV/HCV infection, other acquired or congenital immunodeficiency diseases, and history of organ or allogeneic stem cell transplantation.
• Vaccination with live vaccines within 4 weeks prior to the administration of study drugs or planned vaccination during the study period.
• Prior administration of irinotecan, topotecan, or any other topoisomerase I inhibitors (including investigational topoisomerase I inhibitors), or known history of allergies to the above-mentioned drugs.
• Need for use of any immunosuppressants within 14 days prior to the administration of study drugs or planned use during the study period.

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

Study Sites (1)

Breast Tumor Center, Sun Yat-sen Memorial Hospital

Guangzhou, Guangdong, 510000, China

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Jieqiong Liu

CONTACT

86-13922272706; liujieqiong01@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 17, 2026
• First Posted: February 10, 2026
• Study Start: December 31, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: February 10, 2026

Record last verified: 2026-02

Locations

CN (1)