A Phase 1/2 Study of SY-12321 in Patients With ALK-positive Advanced Malignancies

Inclusion Criteria: * Trial participant voluntarily participates in this study and provides signed written informed consent form (ICF). * Histologically or cytologically confirmed advanced malignancy (locally advanced unresectable or metastatic). * Trial participant is aged ≥ 18 years at the time of signing the ICF. * For trial participants previously treated with an ALK-TKI: subjects are eligible for enrollment if they have a report of ALK-positive result from local laboratory testing \[fluorescence in-situ hybridization (FISH), immunohistochemistry (IHC) (Ventana assay), reverse-transcription polymerase chain reaction (RT-PCR), next-generation sequencing (NGS), and other assays\] using tumor tissue or blood sample obtained within 1 year prior to informed-consent signature. In the absence of such positive report, subjects must provide either non-irradiated archival tissue (collected within 1 year) or fresh biopsy tissue, or fresh blood sample (fresh biopsy tissue and fresh blood are preferred). ALK positivity (ALK fusion and/or other meaningful mutations) must be confirmed by NGS testing performed at the central laboratory for eligibility. For trial participants with no prior ALK-TKI treatment: subjects are eligible for enrollment if they have a prior report of ALK-positive result from local laboratory testing of tumor tissue or blood sample. In the absence of such positive report, subjects must provide either non-irradiated archival tissue or fresh biopsy tissue, or fresh blood sample (fresh biopsy tissue and fresh blood are preferred). ALK positivity must be confirmed by NGS testing performed at the central laboratory for eligibility. Note: Requirements for tumor tissue and blood sample testing are detailed in the \*Central Laboratory Operations Manual. * Phase Ia will enroll trial participants with ALK-positive advanced malignancies who are pretreated. Pretreated is defined as disease progression or intolerance following standard systemic anti-tumor therapy for advanced disease (recommended by clinical oncology practice standards including Chinese Society of Clinical Oncology (CSCO) guidelines and expert consensus); intolerance is defined as recurrence of Grade ≥3 adverse events despite adequate symptomatic treatment with well-documented evidences (corresponding laboratory findings or original medical records from that episode). Phase Ib will enroll two cohorts: Cohort 1: ALK-positive advanced NSCLC previously treated with any second- and/or third-generation ALK-TKI (including investigational agents not yet marketed); Cohort 2: Other pretreated ALK-positive advanced malignancies. Phase Ⅱ will enroll five cohorts: Cohort 1: ALK-positive advanced NSCLC previously treated with any second-generation ALK-TKI (including investigational agents not yet marketed); Cohort 2: ALK-positive advanced NSCLC previously treated with any third-generation ALK-TKI (including investigational agents not yet marketed); Cohort 3: ALK-positive advanced NSCLC previously treated with both second- and third-generation ALK-TKIs (including investigational agents not yet marketed); Cohort 4: ALK-positive advanced NSCLC without prior exposure to any ALK-TKI (including investigational agents not yet marketed); Cohort 5: Other ALK-positive advanced malignancies. * At least one measurable extracranial target lesion per RECIST Version 1.1 (for solid tumors) or other standard tumor response assessment criteria (e.g., the Lugano criteria for trial participants with lymphoma). For previously irradiated lesions, such lesions may serve as target lesions only if clear progression has occurred after radiotherapy. * Expected survival \> 3 months. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Adequate organ function as defined below: Liver function: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3× upper limit of normal (ULN), or ≤ 5× ULN if liver metastasis is present. Total bilirubin (TBIL) ≤ 1.5× ULN, or ≤ 3× ULN if liver metastasis or Gilbert's syndrome is present. Pancreatic function: serum total amylase ≤ 1.5 × upper limit of normal (ULN); serum lipase ≤ 1.5 × ULN. (If serum total amylase \> 1.5 × ULN: enrollment is permitted provided that the trial participant is willing to undergo additional pancreatic amylase testing and the result is within the ULN; enrollment is not allowed if a pancreatic-amylase result within the ULN cannot be obtained.) Bone marrow function (No blood products, hematopoietic growth factors, or other treatments for hematological abnormalities within 7 days prior to testing): Absolute neutrophil count (ANC) ≥ 1.5×10\^9/L. Platelet count (PLT) ≥ 75×10\^9/L. Hemoglobin (Hb) ≥ 90 g/L. Renal function: Creatinine level less than 1.5×upper limit of normal (ULN) or Creatinine clearance ≥ 50 mL/min (according to the Cockcroft and Gault formula). Coagulation function: Prothrombin time (PT) or International Normalized Ratio (INR) ≤ 1.5× ULN (except for subjects on anticoagulation therapy). 10.Female participants of child-bearing potential must have a negative serum pregnancy test result within 7 days prior to the first study drug administration. Male/female participants with reproductive potential and their partners agree to use highly effective contraceptive measures from the time of screening until at least 3 months after the last study drug dose \[1. Abstinence (acceptable only if it is part of the participant's usual lifestyle); 2. Hormonal contraception (oral, patch, ring, injection, implant) combined with male condoms. This contraceptive method must be initiated at least 30 days before the first study drug administration; otherwise, another acceptable contraceptive method shall be adopted; 3. Intrauterine device combined with male condoms\]. Exclusion Criteria: * Presence of known major driver gene alterations (identified in the participant's current genetic testing report) other than ALK, including but not limited to EGFR, MET (note: includin