Eligible patients (aged 18-75, ECOG 0-1) must have advanced solid tumors, measurable lesions per RECIST 1.1, and ≥12-week life expectancy. Exclusions include recent major surgery (within 4 weeks), active CNS metastases, prior malignancies (5 years), steroid use (within 2 weeks), pregnancy/lactation, or conditions compromising study integrity. Contraception is required during and post-treatment.

The primary objectives are to assess DLT (within 21 days of first cycle), determine MTD/RDEs, and monitor AE incidence throughout the trial. Secondary efficacy endpoints include ORR (CR + PR per RECIST 1.1), PFS (time from first dose to PD/death), DoR (response duration from CR/PR to PD), and OS (time from first dose to death), evaluated over 60 months.

This study enrolls patients with histologically confirmed advanced/metastatic solid tumors (Part 1) or HER2-overexpressing breast cancer (Cohort A) and gastric/GEJ adenocarcinoma (Cohort B) (Part 2) who failed prior HER2-targeted therapies. Key requirements include: signed informed consent; LVEF ≥50%; ECOG PS 0-1; life expectancy ≥3 months; adequate hematologic (ANC ≥1.5×10⁹/L, platelets ≥100×10⁹/L, Hb ≥90g/L), hepatic (bilirubin ≤1.5×ULN, AST/ALT ≤3×ULN [≤5×ULN if liver mets]), renal (creatinine ≤1.5×ULN or CrCl ≥60mL/min), and coagulation (INR/PT/APTT ≤1.5×ULN) parameters; measurable lesions (required in Part 2, preferred in Part 1); recovery from prior treatment toxicities (CTCAE v5.0 ≤1); and use of effective contraception. Female participants require negative pregnancy testing within 7 days prior to enrollment.

The study evaluates dose-limiting toxicity (DLT) per NCI CTCAE v5.0 during Cycle 1 (21 days), with maximum tolerated dose (MTD) defined as the highest dose where ≤1 of 3 patients experience DLT within this observation window. Treatment-related adverse events (AEs) and serious adverse events (SAEs) will be monitored for up to 3 years using NCI CTCAE v5.0 criteria, while the recommended Phase II dose (RP2D) will be determined based on Cycle 1 (21-day) safety data.

The study will assess pharmacokinetic (PK) parameters including peak plasma concentration (Cmax), time to peak concentration (Tmax), area under the curve (AUC), half-life (t1/2), and apparent clearance (CL/F) from Cycle 1 to Cycle 10 (21-day cycles). Immunogenicity will be evaluated through anti-drug antibody (ADA) formation up to 18 months. Efficacy measures include objective response rate (ORR), progression-free survival (PFS), and duration of response (DoR) assessed up to 18 months, with overall survival (OS) monitored for up to 3 years. All PK and safety data will be collected during the 21-day treatment cycles.

This clinical trial will evaluate efficacy and safety outcomes over a 24-month period. The primary efficacy endpoint is objective response rate (ORR), defined as the proportion of patients achieving complete response (CR) or partial response (PR) per investigator assessment using RECIST v1.1 criteria. Safety monitoring will include comprehensive evaluation of all adverse events (AEs) and serious adverse events (SAEs), with severity graded according to NCI CTCAE version 5.0 standards throughout the study duration. Both ORR and AE/SAE data will be systematically collected and analyzed to assess the treatment's clinical benefit-risk profile.