A Phase I Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of SON-DP in Subjects With Advanced Solid Tumors
A Phase I Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of SON-DP in Subjects with Advanced Solid Tumors
• Male or female participants aged 18 to 75 years (inclusive).
• For Phase Ia: Participants with histologic diagnosis and confirmed solid tumor; For Phase Ib: Participants with one of the two tumor types: Group 1: advanced primary liver cancer; Group 2: Advanced primary gastric cancer (including gastroesophageal junction adenocarcinoma).
• There must be at least one measurable lesion defined by RECIST v1.1. Lesions intended for biopsy should generally not be selected as target lesions, unless the investigator assesses that the biopsy of the lesion will not affect subsequent tumor evaluations. Lesions that have previously undergone radiation therapy, interventional therapy, or other local treatments should generally not be selected as target lesions, unless the lesion shows clear radiological progression after local treatment.
• The ECOG performance status ≤ 1.
• Able to understand and willing to sign the informed consent form (ICF) and comply with all the requirements of the protocol.
• The investigator assesses that the subject's expected lifespan is greater than 3 months.
• Subjects must be candidates for and agree to the placement of a central venous access line and further must be able, in the opinion of the Investigator, to manage care of this line.
• Subjects with treated brain metastases are allowed but should be neurologically stable (for 4 weeks post-treatment as assessed by CNS imaging and prior to study enrollment) and off steroids for at least 2 weeks before administration of any study treatment.
• All subjects in Phase Ia (with partial exceptions for the first 2 dose levels and designated subjects in Phase Ib must be prepared to undergo 2 or more tumor biopsies, one during the screening period and 1-2 biopsy during therapy. In the Investigator's assessment, these biopsies should be feasible considered, safe by the investigator, and not expected to interfere with all other study assessments.
⁃ Adequate hepatic/renal function as evidenced by meeting all the following requirements:
∙ Total bilirubin ≤ 1.5 × ULN except for subjects with Gilbert's syndrome who are excluded if TBIL \> 3.0×ULN or direct bilirubin \< 1.5×ULN. And there is no evidence of sustained liver function elevation (within 7 days) or acute hepatic decompensation, as assessed by the investigator.
‣ AST \< 3.0×ULN, except for subjects that have tumor involvement of the liver, who are included if AST ≤ 5×ULN. And there is no evidence of sustained liver function elevation (within 7 days) or acute hepatic decompensation, as assessed by the investigator.
‣ ALT ≤ 3.0×ULN, except for subjects that have tumor involvement of the liver, who are included if ALT ≤ 5×ULN. And there is no evidence of sustained liver function elevation (within 7 days) or acute hepatic decompensation, as assessed by the investigator.
‣ Blood Urea Nitrogen (BUN) \< 2.5×ULN.
‣ The calculated creatinine clearance (CrCL) using the Cockcroft-Gault formula must be ≥ 60 mL/min.
⁃ Primary liver cancer: Child-Pugh class A or class B with a score of 7, and no history of hepatic encephalopathy.
⁃ The subject must have adequate bone marrow function (no blood transfusions or hematopoietic growth factor support within 14 days prior to the first dose of SON-DP), with special circumstances to be jointly evaluated by the study team, sponsor, and CRO medical team:
∙ Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L;
‣ Hemoglobin (HGB) ≥ 80 g/L;
‣ Platelet count (PLT) ≥ 75 × 10⁹/L.。
⁃ Coagulation tests within an acceptable range defined by the following:
∙ Activated partial thromboplastin time (APTT) ≤ 1.5×ULN.
‣ International normalized ratio (INR) or Prothrombin Time (PT) ≤ 1.5×ULN. Exception: INR 2 to ≤ 3 ULN is acceptable for subjects on stable therapeutic anticoagulants without active bleeding within 14 days prior to the first dose of the study drug.
⁃ Toxicity related to previous antitumor treatments must have returned to baseline or ≤ grade 1 (NCI-CTCAE 5.0), except for toxicities judged by the investigator to pose no safety risk, such as: hair loss, ≤ grade 2 peripheral neuropathy, thyroid dysfunction stabilized by hormone replacement therapy, or other toxicities that are still grade 2 but are assessed by the investigator as chronic, stable, and with no clear safety concerns.
⁃ Female participants must agree not to breastfeed starting at screening and throughout the study period and for 90 days after final SON-DP administration.
⁃ Fertile, eligible subjects (both male and female) must agree to use reliable contraception methods (hormonal, barrier methods, or abstinence) during the trial and for at least 90 days after the last dose of the medication.