Treatment for HER2-negative breast cancer that is resistant to immune therapy

Reverse HER2-negative Immune Resistant Breast Cancer

This study is testing a new treatment combining retinoic acid with immune therapy and chemotherapy to see if it helps people with advanced HER2-negative breast cancer that hasn't improved with previous treatments.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years to 70 Years
• Sex: Female
• Sponsor: Fudan University (other)
• Drugs / interventions: chemotherapy, immunotherapy, pembrolizumab
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06731140 on ClinicalTrials.gov

What this trial studies

This Phase II, open-label study evaluates the efficacy and safety of combining retinoic acid with immune checkpoint inhibitors in patients with metastatic HER2-negative breast cancer who have progressed after previous immune therapies. The study focuses on both luminal and triple-negative breast cancer subtypes, aiming to address the limited effectiveness of current immunotherapy options in these populations. Participants will receive a combination of retinoic acid, an anti-PD-1 antibody, and chemotherapy to assess potential improvements in treatment outcomes.

Who should consider this trial

Good fit: Ideal candidates include women with metastatic or locally advanced HER2-negative breast cancer who have shown disease progression after prior immunotherapy.

Not a fit: Patients with HER2-positive breast cancer or those who have not previously undergone immune checkpoint inhibitor therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with resistant HER2-negative breast cancer, potentially improving survival rates.

How similar studies have performed: While previous studies have shown limited success with immunotherapy in luminal breast cancer, this approach of combining retinoic acid with immune checkpoint inhibitors is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* ECOG Performance Status of 0, 1, or 2
* Metastatic or locally advanced, histologically confirmed luminal breast cancer (defined as: ER positive when immunohistochemistry shows \>1% positive tumor cells, PR positive when \>1% tumor cells are positive, and HER2 negative when scored as 0-1+ or when HER2 2+ shows no amplification by FISH or CISH) or triple negative breast cancer (defined as: ER negative when immunohistochemistry shows \<1% positive tumor cells, PR negative when \<1% tumor cells are positive, and HER2 negative when scored as 0-1+ or when HER2 2+ shows no amplification by FISH or CISH).
* 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

Where this trial is running

Shanghai, Shanghai Municipality

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

Study contacts

• Study coordinator: Zhimin Shao, Professor

Conditions: HER2 Negative Breast Cancer, immunotherapy, retinoic acid, HER2 negative breast cancer