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

NCT06371274 | Recruiting

• 1 other identifier: ZYYY-IIT-TNBC-001
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Triple-negative Breast Cancer

Keywords

all-trans retinoic acid; Toripalimab; triple-negative breast cancer; efficacy; safety

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  During the combined therapy, tumor assessment (enhanced CT) is conducted every 2 cycles (6 weeks), and the efficacy is evaluated using the RECIST 1.1 criteria. ORR will be summarized as the proportion of subjects achieving objective tumor responses (complete response or partial response). ORR and its 95% confidence interval will be calculated.

  up to 2 years

Secondary Outcomes (3)

• Progression-Free Survival (PFS)

  up to 2 years

• Duration of Response (DOR)

  up to 2 years

• Overall Survival (OS)

  up to 2 years

Other Outcomes (4)

• Incidence of Treatment-Emergent Adverse events as assessed by NCI-CTCAE 5.0

  up to 2 years

• Exploratory biomarkers-peripheral blood lymphocyte analysis

  start from the time of enrollment to the end of the study, assessed up to 2 years

• Exploratory biomarkers-Serum Metabolomics Analysis

  start from the time of enrollment to the end of the study, assessed up to 2 years

Study Arms (1)

ATRA+Toripalimab

EXPERIMENTAL

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.

Drug: ATRA; Drug: Toripalimab

Interventions

ATRA DRUG

ATRA is the main active metabolite of vitamin A. Studies have shown that ATRA can also reduce the number of MDSC in solid tumor patients, promote their differentiation and maturation, remove the immunosuppressive ability of MDSC, improve the tumor immune microenvironment, and thus improve the tumor treatment efficacy.

ATRA+Toripalimab

Toripalimab DRUG

Toripalimab is a fully human monoclonal antibody injection against PD-1 receptor. The NMPA has accepted the application of Toripalimab for a new indication for the treatment of initial metastatic or relapsed metastatic TNBC with PD-L1 positive (CPS≥1).

ATRA+Toripalimab

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years at the time of signing the informed consent form;
• Pathologically confirmed as triple-negative breast cancer based on recent biopsy or other pathological specimens, with histological and/or cytological diagnosis;
• Patients with unresectable locally advanced or metastatic triple-negative breast cancer who have failed at least second-line standard treatment regimens;
• 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);
• 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.

You may not qualify if:

• Known symptomatic or uncontrolled brain metastasis or other central nervous system (CNS) metastases;
• 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;
• Any severe and/or uncontrolled concurrent illness that hinders the patient's participation in the study;
• History of immunodeficiency, autoimmune diseases, the need for immunosuppressive therapy (daily dose \>10 mg of prednisone or equivalent), or a history of chronic infections;
• History of deep vein thrombosis or pulmonary embolism;
• Severe osteoporosis or patients with bone metastases;
• 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;
• Patients with active hepatitis B or C; known history of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS); positive syphilis antibody test;
• History of severe drug allergies or known allergy to any component of the investigational drug as per the prescription;
• The investigator considers the participant unsuitable for the study.

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead
• Shanghai Longfine Biotechnology Co., Ltd.: collaborator
• TopAlliance: collaborator

Study Sites (1)

The first affiliated hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang Province, P.R. China, 310003, China

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

toripalimab

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Xiaochen Zhang, MD

  Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jian Liu, MS

CONTACT

+86-0571-87236537; lindaliu87@zju.edu.cn

Meihua Lin, MS

CONTACT

mhlin2015@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief pharmacist

Study Record Dates

• First Submitted: April 2, 2024
• First Posted: April 17, 2024
• Study Start: October 10, 2024
• Primary Completion: April 30, 2026
• Study Completion: April 30, 2026
• Last Updated: August 12, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)