A Study on the Efficacy and Safety of Oral All-trans Retinoic Acid Combined With Toripalimab in TNBC.

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.

To evaluate the clinical efficacy and safety of oral all-trans retinoic acid in combination with toripalimab in patients with locally advanced, recurrent, or metastatic triple-negative breast cancer who had failed second-line and subsequent therapy.

The study is designed as a single arm, open-label, mono-center exploratory trial, aiming to evaluate the clinical efficacy and safety of oral all-trans retinoic acid in combination with toripalimab in patients with locally advanced, unresectable, recurrent, or metastatic triple-negative breast cancer who had failed second-line and subsequent standard treatments. 32 subjects are planned to be enrolled. Eligible participants are subjected to take all-trans retinoic acid orally at a dose of 150 mg/m2 per day, twice a day for three consecutive days per cycle (d0~d2), and intravenous infusion of PD-1 monoclonal antibody at a dose of 240 mg on day 1 of each cycle (d1), with cycles repeated every 3 weeks until disease progression, death, loss to follow-up, intolerable toxicity, or meeting other withdrawal or termination criteria (whichever occurs first), for a maximum duration of 2 years. Each subject's study process includes a screening period (within 28 days), a treatment period, and a follow-up period. Subjects will sign the informed consent form and complete all baseline assessments during the screening period. Qualified subjects will enter the treatment period, followed by the survival follow-up every 3 months after the completion of the treatment period. Tumor assessments (contrast-enhanced CT) will be conducted every 2 cycles (6 weeks) during the combination treatment period, and efficacy evaluation will be based on RECIST 1.1 criteria. Moreover, iORR and iPFS were assessed by investigators based on iRECIST criteria. Adverse events will be assessed using NCI-CTCAE version 5.0, with observation of adverse events up to 30 days after the last treatment.

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.