Primary Objectives Phase Ib To evaluate the safety and tolerability of Purinostat Mesylate in combination therapy for advanced solid tumors; and to explore the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of Purinostat Mesylate in combination therapy in patients with advanced solid tumors.
To determine the recommended Phase II dose (RP2D) of Purinostat Mesylate in combination therapy for advanced solid tumors.
Phase IIa To further evaluate the preliminary efficacy of Purinostat Mesylate in combination therapy in patients with advanced solid tumors.
Secondary Objectives Phase Ib To evaluate the safety and tolerability of Purinostat Mesylate Monotherapy for the treatment of advanced solid tumors; To evaluate the preliminary efficacy of Purinostat Mesylate in combination therapy in patients with advanced solid tumors; To evaluate the pharmacokinetic characteristics of Purinostat Mesylate in combination therapy for the treatment of advanced solid tumors.
Phase IIa To further evaluate the safety and tolerability of Purinostat Mesylate in combination therapy for advanced solid tumors.
To evaluate the pharmacokinetic characteristics of Purinostat Mesylate in combination therapy for advanced solid tumors.
Exploratory Objectives To assess the pharmacodynamic characteristics in Purinostat Mesylate combination therapy for advanced solid tumors.
Age: ≥18 years and ≤75 years, regardless of gender.
At least one measurable lesion as defined by RECIST 1.1 during the screening period (for the breast cancer cohort in the dose-escalation phase, measurable lesions are not required if the participant has only bone metastases).
Histologically or cytologically confirmed breast cancer in perimenopausal, premenopausal, or postmenopausal women with estrogen receptor (ER)-positive, progesterone receptor (PgR)-negative or positive, and non-HER2-positive (including HER2-negative and low-expression) disease.
Participants must have progressed or recurred after at least one line of endocrine therapy (regardless of whether it was in the advanced, metastatic, or neoadjuvant chemotherapy setting), with up to two lines of prior chemotherapy allowed.
Known severe allergy to the investigational drug, any of the combination drugs, or any of their excipients (hydroxypropyl-beta-cyclodextrin, arginine, tromethamine, mannitol).
Presence or history of other malignancies (except adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, or cervical carcinoma in situ), unless the participant has undergone curative treatment and has evidence of no recurrence or metastasis within the past 5 years.
Symptomatic central nervous system (CNS) metastases or CNS metastases requiring corticosteroid treatment within 2 weeks before the first dose of the study drug. Participants with asymptomatic CNS metastases are also excluded. Participants with leptomeningeal carcinomatosis or meningeal dissemination are excluded.
Received mitomycin C or nitrosourea chemotherapy (e.g., carmustine, lomustine) within 6 weeks before the first dose.
Sequential
A0/B0 group Purinostat Mesylate 11.2mg/m2
DrugPurinostat Mesylate 11.2mg/m2
A0/B0 group Purinostat Mesylate 15mg/m2
DrugPurinostat Mesylate 15mg/m2
A group Purinostat Mesylate 6mg/m2
DrugPurinostat Mesylate 6mg/m2 + FS 500mg
A group Purinostat Mesylate 8.4mg/m2
DrugPurinostat Mesylate 8.4mg/m2 + FS 500mg
A group Purinostat Mesylate 11.2mg/m2
DrugPurinostat Mesylate 11.2mg/m2 + FS 500mg
A group Purinostat Mesylate 15 mg/m2
DrugPurinostat Mesylate 15 mg/m2 + FS 500mg
B group Purinostat Mesylate 6 mg/m2
DrugPurinostat Mesylate 6mg/m2 + Tislelizumab 200mg
B group Purinostat Mesylate 8.4 mg/m2
DrugPurinostat Mesylate 8.4mg/m2 + Tislelizumab 200mg
B group Purinostat Mesylate 11.2mg/m2
DrugPurinostat Mesylate 11.2mg/m2 + Tislelizumab 200mg
B group Purinostat Mesylate 15mg/m2
DrugPurinostat Mesylate 15mg/m2 + Tislelizumab 200mg
Objective remission rate (ORR)
defined as the proportion of subjects with an overall efficacy response of complete remission (CR) or partial remission (PR) after at least one post-baseline evaluation during the trial.
Complete Remission Rate (CRR)
defined as the proportion of subjects with an overall efficacy response of CR after at least one post-baseline evaluation during the trial;
Disease Control Rate (DCR)
defined as the proportion of subjects with an overall efficacy response of CR, PR and stable disease (SD) after at least one post-baseline evaluation during the trial;
Duration of remission (DOR)
defined as the duration from first remission (PR and CR) to disease progression or death;
Time to Tumor Remission (TTR)
defined as the time from first dose to the appearance of PR or CR;
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