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

ConditionsTriple -Negative Breast Cancer Breast Cancer

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18-70

SponsorSun Yat-Sen Memorial Hospital of Sun Yat-Sen University

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

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).
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).

Treatment groups

416 Participants

are divided into 2 treatment groups

Group A: Extended-Dose IntervalExperimental treatment 1 intervention

Group B: Standard-Dose IntervalActive comparator 1 intervention

Trial outcomes

Primary outcomes

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.

Time frame

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

mOS

The time from randomization date to any cause of death date.

Time frame

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

DoR

Refers to the time from the date of achieving CR or PR to the first disease progression (PD) or death from any cause, whichever occurs first.

Time frame

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

Refers to the time from the date of achieving CR, PR, or SD to the first evaluation as PD or death from any cause, whichever occurs first.

Time frame

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.

Patient reported outcomes via the European Organisation for Research and Treatment of Cancer Core Quality of Life questionnaire (EORTC QLQ-C30). It contains 30 items and measures 5 functional scales (physical, role, emotional, cognitive, and social), a global health and quality of life scale, 3 symptom scales (fatigue, nausea/vomiting, and pain), and 6 single items (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact). The global health and quality of life scale uses a 7-point scale scoring with anchors (1=very poor and 7=excellent); the other items are scored on a 4 point scale (1=not at all, 2=a little, 3= quite a bit, 4=very much).

Time frame

3 years.

Other outcomes

Biomarker

Compare the differences in immune cell proportion, PD-1 saturation and other aspects among blood and tissue samples in both arms to identify biomarkers that may predict treatment outcomes.

Time frame

3 years (before and after therapy).

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Lead sponsor

Source ClinicalTrials.gov

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