DCSZ11 in Combination With Standard Therapy in Advanced or Metastatic Solid Tumors

Inclusion Criteria32

• Male or female patients aged ≥18 years.
• Willing and able to provide written informed consent for the study.
• Patients with histologically confirmed advanced or metastatic solid tumors. Note: Patients must have guideline-eligible standard chemotherapy and immunotherapy options available.Patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) must have PD-L1 Combined Positive Score (CPS) ≥1.Lung cancer patients with known actionable driver gene mutations/genomic aberrations (e.g., EGFR sensitizing mutations, BRAF V600E mutation, ROS1 rearrangements, NTRK gene fusions, ALK rearrangements) are excluded.Prior adjuvant or neoadjuvant chemotherapy is permitted, provided ≥6 months have elapsed between the last dose of chemotherapy/immunotherapy and documented recurrent disease.Gastric cancer patients must be HER2-negative.
• Patients must have at least one measurable lesion per RECIST 1.1 criteria. Lesions located in previously irradiated areas may be considered measurable if there is objective evidence of progression in those lesions prior to study enrollment.
• Patients with previously treated central nervous system (CNS) metastases are eligible provided they meet all the following criteria:
• Stability (i.e., no evidence of progression on magnetic resonance imaging \[MRI\]) for ≥4 weeks prior to the first dose of study drug, and
• All neurological symptoms have returned to baseline, and
• No requirement for steroid therapy for at least 14 days prior to the first dose of study intervention.
• Patients with signs or symptoms suggestive of CNS metastases must undergo brain imaging within 2 weeks prior to the first dose of study drug to confirm the absence of detectable CNS disease.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function and bone marrow reserve per laboratory assessments within 10 days prior to first study drug administration:
• Bone marrow function:
• Absolute neutrophil count (ANC) ≥1,500/µL
• Hemoglobin ≥9 g/dL (must be achieved without erythropoietin dependency AND without packed red blood cell \[pRBC\] transfusion within the preceding 2 weeks)
• Platelet count ≥100,000/µL
• Hepatic function:
• Total serum bilirubin ≤1.5 × upper limit of normal (ULN); or direct bilirubin ≤ULN for patients with total bilirubin \>1.5 × ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN (≤5 × ULN if liver metastases present)
• Renal function:
• Estimated creatinine clearance ≥30 mL/min (per Cockcroft-Gault formula)
• PD-L1 status must be available for all patients via approved immunohistochemistry assay.
• Resolution of all prior treatment-related toxicities to Grade ≤1 or baseline, or determination as irreversible sequelae.
• \*Note: Grade ≤2 neuropathy and/or hearing loss, alopecia of any grade, or autoimmune endocrinopathies on stable replacement therapy are permitted.\*
• Female patients must agree to refrain from breastfeeding for 5 months after last study dose and satisfy one of:
• Postmenopausal for ≥1 year prior to screening, or
• Surgically sterile, or
• Agreement to use one highly effective contraceptive method plus one additional barrier method from signing informed consent form (ICF) until 5 months after last study dose, or
• Practice true abstinence\* when consistent with preferred lifestyle Periodic abstinence, withdrawal, spermicide-only, or lactational amenorrhea are unacceptable. Female/male condoms must not be used concomitantly.
• Male patients, even surgically sterilized (i.e., post-vasectomy), must agree to either:
• Use effective barrier contraception from ICF signing until 2 months after last DCSZ11 dose, or
• Practice true abstinence\* when consistent with preferred lifestyle Exclusions as per Criterion 10.
• Willingness and ability to comply with scheduled visits and procedures per protocol.