Oral all-trans retinoic acid plus toripalimab for advanced or metastatic triple-negative breast cancer

Efficacy and Safety Study of Oral All-trans Retinoic Acid Combined With Toripalimab in Patients With Inoperable Locally Advanced, Recurrent, or Metastatic Triple-negative Breast Cancer Who Had Failed Prior Second-line or Higher Standard Therapy.

This test tries whether taking oral all‑trans retinoic acid together with the immunotherapy toripalimab helps people with locally advanced, recurrent, or metastatic triple‑negative breast cancer who have failed at least two prior treatments.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 29 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: First Affiliated Hospital of Zhejiang University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone, toripalimab
• Locations: 1 site (Hangzhou, Zhejiang Province, P.R. China)
• Trial ID: NCT06371274 on ClinicalTrials.gov

What this trial studies

This is a single-arm, open-label, single-center exploratory trial enrolling about 32 patients with unresectable, recurrent, or metastatic triple‑negative breast cancer after at least two prior standard regimens. Participants take oral all‑trans retinoic acid on days 0–2 of each 3‑week cycle and receive 240 mg toripalimab by IV on day 1, with treatment continued until progression, unacceptable toxicity, or for up to two years. Tumor response is measured by contrast-enhanced CT every two cycles (about every 6 weeks) and evaluated using RECIST 1.1 criteria, with immune-related response measures such as iORR and iPFS also recorded. Safety and tolerability are monitored throughout treatment and during scheduled follow-up visits every three months after treatment ends.

Who should consider this trial

Good fit: Adults (≥18) with pathologically confirmed triple‑negative breast cancer that is unresectable, recurrent, or metastatic, who have progressed after at least two prior standard treatment regimens, have at least one measurable lesion by RECIST 1.1, and have adequate organ and bone marrow function.

Not a fit: Patients with only skin‑only or bone‑only disease, uncontrolled medical conditions, inadequate organ function, or who have not yet received prior standard therapies are unlikely to qualify or benefit from this treatment approach.

Why it matters

Potential benefit: If successful, the combination could provide a new option that shrinks tumors or delays progression in heavily pretreated triple‑negative breast cancer patients.

How similar studies have performed: Combining retinoids with PD‑1 inhibitors has biological rationale and limited early-phase signals, but this exact oral ATRA plus toripalimab combination in heavily pretreated TNBC remains exploratory and not yet established.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years at the time of signing the informed consent form;
2. Pathologically confirmed as triple-negative breast cancer based on recent biopsy or other pathological specimens, with histological and/or cytological diagnosis;
3. Patients with unresectable locally advanced or metastatic triple-negative breast cancer who have failed at least second-line standard treatment regimens;
4. According to RECIST 1.1, at least one measurable lesion is required. Patients with only skin lesions or bone lesions are not eligible for inclusion;
5. Adequate organ and bone marrow function (not received blood transfusions, recombinant human platelet growth factor, or colony-stimulating factor treatment in the 2 weeks before screening);
6. The subject voluntarily agrees to participate in this study, signs the informed consent form, and is able to comply with the visits and related procedures specified in the protocol.

Exclusion Criteria:

1. Known symptomatic or uncontrolled brain metastasis or other central nervous system (CNS) metastases;
2. Patients with other malignant tumors, excluding those with cured basal cell or squamous cell skin carcinoma or in situ cervical cancer. Patients with other malignant tumors must have a disease-free interval of at least 5 years;
3. Any severe and/or uncontrolled concurrent illness that hinders the patient's participation in the study;
4. History of immunodeficiency, autoimmune diseases, the need for immunosuppressive therapy (daily dose \>10 mg of prednisone or equivalent), or a history of chronic infections;
5. History of deep vein thrombosis or pulmonary embolism;
6. Severe osteoporosis or patients with bone metastases;
7. Participants who, within the first 4 weeks before the initiation of the study treatment or during the 5 half-lives of any drugs used in the pre-study period (whichever is shorter), have received any chemotherapy, immunotherapy, biologic therapy, or participated in other drug clinical trials, or received traditional Chinese medicine preparations for the treatment of approved anticancer indications or radiotherapy within the first 2 weeks before the initiation of the study treatment, or have undergone major surgery within the first 4 weeks before the initiation of the study treatment;
8. Patients with active hepatitis B or C; known history of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS); positive syphilis antibody test;
9. History of severe drug allergies or known allergy to any component of the investigational drug as per the prescription;
10. The investigator considers the participant unsuitable for the study.

Where this trial is running

Hangzhou, Zhejiang Province, P.R. China

• The first affiliated hospital, Zhejiang University School of Medicine — Hangzhou, Zhejiang Province, P.R. China, China (Recruiting)

Study contacts

• Principal investigator: Xiaochen Zhang, MD — Zhejiang University
• Study coordinator: Jian Liu, MS

Conditions Triple-negative Breast Cancer; all-trans retinoic acid; Toripalimab; triple-negative breast cancer; efficacy; safety