Reversing immune resistance in triple-negative breast cancer

Reverse Triple Negative Immune Resistant Breast Cancer

This Phase II will test whether adding several drugs (like choline, sodium cromoglicate, efavirenz, SHR compounds, and theophylline) to an anti–PD‑1 treatment can overcome resistance in people with metastatic triple‑negative breast cancer that progressed after prior immunotherapy.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years to 70 Years
• Sex: Female
• Sponsor: Fudan University (other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Shanghai)
• Trial ID: NCT05076682 on ClinicalTrials.gov

What this trial studies

This Phase II, open‑label, three‑arm parallel study enrolls people with metastatic or locally advanced triple‑negative breast cancer who progressed during or after prior immune checkpoint inhibitor therapy. Participants receive combinations of repurposed and investigational agents (including choline, sodium cromoglicate, efavirenz, SHR‑A1811, SHR‑2102, mecapegfilgrastim and theophylline) alongside an anti‑PD‑1 antibody or an anti‑PD‑1 rechallenge (AK131) to modulate the tumor immune microenvironment. The main goals are to test safety and tumor response using RECIST v1.1 measurable disease criteria, with regular imaging and laboratory monitoring and predefined safety rules. The design is based on preclinical data showing these agents can enhance PD‑1 efficacy in mouse models and on promising subgroup responses from prior clinical work in the IM subtype of TNBC, and it is conducted at Fudan University Shanghai Cancer Center.

Who should consider this trial

Good fit: Ideal candidates are adults with metastatic or locally advanced triple‑negative breast cancer, measurable disease, ECOG 0–2, adequate organ function, and documented progression during or after prior immunotherapy who can travel to the study center and consent to follow‑up.

Not a fit: People with symptomatic untreated or actively progressing central nervous system metastases, active autoimmune disease, or poor organ function (or who cannot travel to Shanghai) are unlikely to enroll or benefit from the interventions.

Why it matters

Potential benefit: If successful, the combination could restore sensitivity to immunotherapy and produce meaningful tumor responses or disease control in patients whose TNBC no longer responds to PD‑1 inhibitors.

How similar studies have performed: Prior work (the FUTURE program) showed a high objective response rate (52.6%) in the immunomodulatory TNBC subtype, but the specific drug combinations here are largely supported by preclinical data and remain clinically unproven.

Eligibility criteria

Inclusion Criteria:

* ECOG Performance Status of 0, 1, or 2
* Metastatic or locally advanced, histologically documented TNBC (absence of HER2, ER, and PR expression)
* Radiologic/objective evidence of recurrence or disease progression after immunotherapy(combined with targeted therapy or chemo ) for metastatic breast cancer(MBC)
* Adequate hematologic and end-organ function, laboratory test results, obtained within 14 days prior to initiation of study treatment.
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures as outlined for each specific treatment arm
* Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1)
* have the cognitive ability to understand the protocol and be willing to participate and to be followed up.

Exclusion Criteria:

* Symptomatic, untreated, or actively progressing CNS metastases
* Active or history of autoimmune disease or immune deficiency
* Significant cardiovascular disease
* History of malignancy other than breast cancer within 5 years prior to screening, with the exception of those with a negligible risk of metastasis or death
* Treatment with chemotherapy, radiotherapy,immunotherapy or surgery (outpatient clinic surgery excluded) within 3 weeks prior to initiation of study treatment.
* Pregnancy or breastfeeding, or intention of becoming pregnant during the study
* History of allergies to the drug components of this trial
* History of eosinophilosis or mastocytosis
* Patients who have been using oral steroid hormones for a long time will need to stop for 4 weeks if they have used them occasionally in the past
* For the Mecapegfilgrastim group, patients had previously received PEG-rhG-CSF in combination with immunotherapy.

Where this trial is running

Shanghai

• Fudan University Shanghai Cancer Center — Shanghai, China (RECRUITING)

Study contacts

• Principal investigator: Zhimin Shao, Professor — Fudan U
• Study coordinator: Zhimin Shao, Professor

Conditions: Triple-negative Breast Cancer, TNBC, molecular subtype, precision Treatment, immunotherapy, choline, sodium cromoglicate, efavirenz