Eligible patients (18-75yo females) must have HER2+ metastatic breast cancer refractory to anti-HER2 therapy with ECOG 0-1, adequate organ function, and measurable disease. Key exclusions include recent anti-HER2 therapy (T-DM1/trastuzumab within 3 months), anthracycline overdose (doxorubicin >450mg/m2 equivalent), uncontrolled comorbidities (cardiac dysfunction LVEF<50%, NYHA III-IV, uncontrolled HTN, active bleeding disorders), hepatitis/HIV, symptomatic brain metastases, or lab abnormalities (neutrophils <1.5&times;109/L, platelets <100&times;109/L, ALT/AST >2.5&times;ULN). Pregnancy prevention is mandatory for 6 months post-treatment.

The study will determine the MTD of B003 over 2 years by assessing DLTs during the first 21-day cycle, with extensive PK profiling including Tmax, Cmax, t½, MRT, AUC, elimination rate and CL/F. Immunogenicity will track ADA incidence and titers, while efficacy endpoints measure ORR, DCR, DOR and PFS over 14 months per RECIST v1.1 criteria, requiring confirmation of responses at 4 weeks.

Eligible patients (18-75 years, ECOG 0-1) must have failed standard therapy, measurable lesions, adequate organ function, and controlled toxicities. Exclusion criteria involve recent chemotherapy/radiotherapy, severe comorbidities, active infections, CNS metastases, unresolved ILD, or prior topoisomerase I inhibitors. Strict lab and clinical stability requirements apply.

Eligible participants (18-75 years) must have locally advanced/metastatic gastrointestinal cancer, measurable lesions (RECIST 1.1), ECOG 0-1, and adequate organ function. Key exclusions: prior topoisomerase I inhibitor ADCs, recent antitumor therapy (4 weeks/5 half-lives), severe cardiac/autoimmune diseases, active infections, uncontrolled effusions, CNS metastases, or conditions compromising trial safety per investigator judgment.

Eligible patients (18-75 years) must have locally advanced/metastatic head and neck squamous cell carcinoma (excluding nasopharyngeal primary), measurable lesions (RECIST 1.1), ECOG &le;1, and adequate organ function. Key exclusions: active CNS metastases, recent anticancer therapy (4 weeks/5 half-lives), uncontrolled hypertension/cardiac conditions, autoimmune diseases, organ transplant history, HIV/HBV/HCV infection, or prior grade &ge;3 immune-related adverse events from immunotherapy.

The Phase Ib study evaluates dose-limiting toxicity (DLT) and determines the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) for SI-B001+SI-B003 combination therapy based on safety, efficacy, and pharmacokinetic data. Primary efficacy endpoint is objective response rate (ORR), defined per RECIST 1.1 as complete/partial response rates through 24 months.

Safety and efficacy outcomes include treatment-emergent adverse events (TEAEs), disease control rate (DCR), duration of response (DOR), and progression-free survival (PFS) across both phases. Pharmacokinetic measures - Cmax, Tmax, half-life (T1/2), AUC, clearance (CL), trough levels (Ctrough) - and immunogenicity (anti-drug/neutralizing antibodies) will be analyzed for both investigational compounds.

Eligible participants (18-75 years) must have recurrent/metastatic HNSCC (excluding nasopharyngeal) with measurable lesions (RECIST 1.1), ECOG 0-1, and adequate organ function. Key exclusions: prior topoisomerase I inhibitor ADC treatment, recent anticancer therapy (4 weeks/5 half-lives), uncontrolled cardiovascular/autoimmune conditions, active infections, symptomatic CNS metastases/effusions, or positive HIV/HBV/HCV status with high viral loads.

Eligible patients (18-75 years) must have recurrent/metastatic HNSCC (excluding nasopharyngeal origin) with measurable lesions (RECIST 1.1), ECOG &le;1, adequate organ function, and controlled prior treatment toxicities. Key exclusions: active CNS metastases, recent anticancer therapy/immunization (4 weeks), uncontrolled infections/autoimmune diseases, effusions requiring drainage, severe cardiovascular conditions, HIV/HBV/HCV positivity with high viral load, or prior grade &ge;3 immune-related adverse events from immunotherapy.

Secondary outcomes include progression-free survival (time to progression/death), disease control rate (complete/partial response or stable disease), duration of response (sustained treatment effect), treatment-emergent adverse events (safety profile), pharmacokinetic parameters (Cmax, Tmax, Ctrough), and immunogenicity assessment (anti-drug antibody frequency/titer).

Eligible patients (18-75 years, ECOG 0-1) must have locally advanced/metastatic solid tumors (NSCLC, nasopharyngeal carcinoma) with measurable lesions (RECIST v1.1) and adequate organ function. Key exclusions: MET exon 14 skipping mutations (Cohort_A), recent anticancer therapy (4 weeks/5 half-lives), uncontrolled hypertension/infections, active CNS metastases, &ge;grade 3 immunotherapy-related toxicities, autoimmune/inflammatory diseases, significant effusions, or HIV/HBV/HCV infections with active viral replication.

Eligible patients (18-75 years, ECOG 0-1) must have extensive-stage small-cell lung cancer (SCLC) confirmed histologically/cytologically, with measurable lesions and adequate organ function. Key exclusions: prior HER3/EGFR antibody therapy, recent anticancer treatment (4 weeks/5 half-lives), uncontrolled hypertension/diabetes, active infections, CNS metastases requiring intervention, autoimmune diseases, or other malignancies within 5 years. Cohort-specific criteria apply for prior therapy lines (Cohort_A: &ge;3 lines; Cohort_B: standard therapy failure or treatment-na&iuml;ve).

Secondary endpoints comprise Progression-Free Survival (time from treatment initiation to disease progression/death), Disease Control Rate (percentage with response/stable disease per RECIST 1.1), Duration of Response (sustained treatment benefit), and Treatment-Emergent Adverse Events (incidence/severity of new/worsened conditions), all evaluated during the 24-month study period.

Eligible patients (18-75 years, ECOG 0-1) must have histologically confirmed locally advanced/metastatic NSCLC (Phase Ib: driver-negative post-standard therapy; Phase II Cohort_A: untreated driver-negative; Cohort_B: EGFRmut post-TKI failure). Key exclusions: actionable mutations (ALK/MET/ROS1/BRAF/NTRK/RET), uncontrolled CNS metastases, recent immunotherapy with &ge;G3 irAE, active infections, autoimmunity, or other malignancies within 5 years. Required: measurable lesions, adequate organ function, and ctDNA testing for EGFR/ALK/MET/ROS1/BRAF/NTRK/RET/HER2/KRAS. PD-L1 testing mandated for Phase II Cohort_A.

Phase Ib/II primary endpoints include determining the Recommended Phase II Dose (RP2D) of SI-B001+SI-B003 based on safety, tolerability, efficacy, PK, and PD data. Objective Response Rate (ORR) per RECIST 1.1 assesses confirmed CR/PR rates. Phase Ib evaluates Dose-Limited Toxicity (DLT) incidence/severity via NCI-CTCAE v5.0 and Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) based on DLT rates.

Secondary endpoints include Treatment-Emergent Adverse Events (TEAEs), Disease Control Rate (DCR), Duration of Response (DOR), and Progression-Free Survival (PFS). Pharmacokinetic parameters (Cmax, Tmax, Ctrough, T1/2, AUC0-t, CL) and immunogenicity (anti-drug/neutralizing antibodies) are also analyzed over 24 months to assess drug exposure and immune response.

Eligible patients (Phase Ia: &ge;18-75 years; Phase Ib: &ge;18 years) must have recurrent/metastatic solid tumors (Phase Ib: gastric/GEJ adenocarcinoma post-platinum/anti-PD- (L)1 or mesothelioma), measurable lesions (Phase Ib), ECOG 0-1, and adequate organ function. Key exclusions: symptomatic CNS metastases, recent anticancer therapy (4 weeks/5 half-lives), uncontrolled infections/autoimmunity, HIV/HBV/HCV, QTc prolongation, or anthracycline exposure >360 mg/m2.

Phase Ia evaluates Dose-Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD)/Maximum Administered Dose (MAD) of SI-B003 within 28 days post-dose using NCI-CTCAE v5.0 criteria. Phase Ib determines the Recommended Phase II Dose (RP2D) based on safety, tolerability, efficacy, PK/PD data, while Treatment-Emergent Adverse Events (TEAEs) are monitored over 24 months.

Eligible patients (&ge;18-75 years, ECOG 0-1) must have advanced/metastatic solid tumors (urothelial/prostate/renal cancers post-standard therapy failure/intolerance) with measurable lesions (RECIST 1.1). Key exclusions: prior topoisomerase I inhibitor ADC use, recent chemotherapy/radiotherapy (4 weeks/5 half-lives), unstable CVD, active autoimmunity/infections, uncontrolled diabetes/hypertension, CNS metastases (unless stable post-treatment), or serous effusion requiring drainage. Organ function thresholds: Hb &ge;90g/L, ANC &ge;1.5&times;10⁹/L, platelets &ge;100&times;10⁹/L, Cr &le;1.5 ULN (Ccr &ge;40 mL/min), LVEF &ge;50%. HIV/HBV/HCV active infections disqualify.