A Study of HS248 in Patients With Advanced Solid Tumors

A Phase I Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of HS248 in the Treatment of Patients With Advanced Solid Tumors

This study is a non-random, open multi-center study This study is a non-random, open multi-center phase I study, aimed at evaluation period research, aimed at In the evaluation phase study, it aims to evaluate the safety, tolerance PK characteristics and preliminary anti-tumor activity of HS248 in patients with advanced solid tumors. The study was divided into 2 phases, including dose escalation and dose expansion。

Main purpose:

Assess the safety and tolerability of HS248 in patients with advanced solid tumors, and determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of HS248.

Secondary purpose: Secondary purpose:

Assess the pharmacokinetic (PK) profile of HS248 in patients with advanced solid tumors; To evaluate the preliminary antitumor activity of HS248 in patients with advanced solid tumors. Preliminary antitumor activity in patients with advanced solid tumors.

Other purposes:

Population-based PK (PopPK) analysis method, exploratory description) analysis method, exploratory description) analysis method, exploratory description) analysis method, exploratory description of HS248 in patients with advanced solid tumors PK features in; Evaluate the relationship between exposure and efficacy and adverse events (AEs) of HS248 in patients with advanced solid tumors, as data permit; To explore the changes of HS248 in myeloid-derived suppressor cells (MDSC) and CD8+ T cells in patients with advanced solid tumors.

Inclusion Criteria:

1. Voluntarily participate in this clinical trial, understand and follow the research procedures and voluntarily sign the ICF;
2. Male or female, age ≥18 when signing the ICF;
3. Expected survival period ≥ 12 weeks;
4. Patients with advanced solid tumors confirmed by histology/cytology, who have progressed through standard treatment, have toxicity intolerance, or have no standard treatment plan (patients with multiple solid tumors are included in the dose-escalation phase, and the population included in the dose-expansion phase will be based on dose escalation phase study data and the potential advantageous population of similar drugs);
5. Eastern Cooperative Oncology Group (ECOG) physical status score 0-1

Exclusion Criteria:

1. Symptomatic or untreated central nervous system metastasis or primary central nervous system malignancy;
2. Other known malignant tumors in the past 5 years, except cured localized tumors, including carcinoma in situ of the cervix, basal cell carcinoma of the skin, and carcinoma in situ of the prostate;
3. Previous history of autoimmune diseases, stem cell transplantation or organ transplantation;
4. Known drug-induced liver injury, chronic active hepatitis, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, persistent extrahepatic obstruction caused by gallstones, cirrhosis or portal hypertension;
5. Peptic ulcer and/or gastrointestinal bleeding at present or in the past;
6. Gastrointestinal dysfunction that may limit the absorption of the test drug, including motility disorders, malabsorption syndrome or inflammatory bowel disease;