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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
29
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.
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).
The first affiliated hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang Province, P.R. China, China
RECRUITINGObjective 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.
Time frame: up to 2 years
Progression-Free Survival (PFS)
PFS defined as the time from enrollment until disease progression or death (whichever occurs first).
Time frame: up to 2 years
Duration of Response (DOR)
For responders (complete response or partial response), DOR is defined as the time from the earliest date meeting the response criteria to disease progression or death for any reason (whichever occurs first). For subjects who do not experience progression after meeting response criteria and continue to survive, DOR will be censored at the last evaluable tumor assessment date or the last follow-up date for disease progression.
Time frame: up to 2 years
Overall Survival (OS)
OS is defined as the time interval between the date of the first dose and the date of death for any reason. Kaplan-Meier methodology will be used to estimate median OS, OS rates, and their 95% confidence intervals at different time points.
Time frame: up to 2 years
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