Eligible patients must have advanced/metastatic gastric/GEJ adenocarcinoma or colorectal cancer (refractory to standard therapy) with ≥1 measurable lesion (RECIST 1.1), ECOG 0-1, life expectancy ≥3 months, and adequate organ function. Exclusions: unresolved Grade >1 toxicities, prior HER2-ADC exposure, symptomatic CNS/meningeal metastases, or active infections requiring systemic treatment.

Phase 1 evaluates safety/tolerability of SHR-A1811 through incidence/severity of AEs (CTCAE v5.0; monitored Day1-90 post-last dose, ~3 years), MTD determination (DLTs in first 21-day cycle), and RP2D selection (based on safety/PK/efficacy over 12 months). Phase 2 primary endpoint is ORR (RECIST v1.1, IRC-assessed, tumor imaging q6w→q12w post-54w until progression/new therapy/death, ~3 years).

Eligible participants (signed ICF, ECOG 0-1, life expectancy ≥12 weeks) must have measurable advanced/recurrent cervical, ovarian, or endometrial cancer. Exclusions: untreated CNS metastases, prior topoisomerase I inhibitor ADC treatment (e.g., DS-8201a), uncontrolled cardiovascular disease, active autoimmune/HBV/HCV infections, recent severe infections (28 days), or active tuberculosis (1 year).

Eligible patients (women 18-75 years, ECOG 0-1) require histologically confirmed HER2+ breast cancer, measurable lesions (RECIST v1.1), and adequate organ function. Key exclusions: active CNS metastases (unless treated), uncontrolled effusions, recent antitumor therapy (≤4 weeks), autoimmune/cardiovascular diseases, or unresolved toxicity (>CTCAE Gr1). Hepatitis B/C carriers with viral loads >2000 IU/mL or cirrhosis are excluded.

Eligible patients aged 18-70 have untreated T2-T3/N0-3/M0, HR+/HER2-low (Ki-67 >14%) invasive breast cancer (ECOG 0-1) and normal organ function. Exclusions: metastatic/inflammatory disease, prior anticancer therapy (excluding cured non-breast malignancies), recent major surgery, severe comorbidities (cardiopulmonary/immunodeficiency), drug allergies, or conditions impairing treatment adherence. WOCBP must use contraception.

Eligible participants are females ≥18 with HER2+/HER2-low advanced breast cancer and measurable untreated intracranial lesions (RANO-BM). Key criteria: no prior cranial radiation/local therapy (unless post-surgery, unirradiated), ≥2 weeks since last systemic treatment, life expectancy ≥6 months, and adequate organ function. Exclusions: leptomeningeal disease, urgent CNS intervention needed, prior DS-8201a/exatecan-ADC use, recent antitumor therapy (≤2 weeks for most, ≤1 week for endocrine), other malignancies (except cured CIS/skin cancers), or uncontrolled comorbidities per investigator judgement.

Eligible patients (18-75 years, ECOG 0-1, life expectancy ≥12 weeks) must have histologically confirmed locally advanced/metastatic salivary gland carcinoma: Arm 1 (HER2-altered), Arm 2 (AR-positive), Arm 3 (HER2/AR-negative), or Arm 4 (low HER2 expression), with ≥1 measurable lesion (RECIST v1.1). Key exclusions: active malignancies (5 years), recent antitumor therapy (28 days prior, or <5 half-lives), uncontrolled cardiac conditions (NYHA ≥II, LVEF <50%, QTc >450ms♂/470ms♀), uncontrolled hypertension, gastrointestinal absorption issues (Arm 2), bleeding risks, or abnormal coagulation (INR/aPTT >1.5×ULN). Organ function thresholds: HB ≥90g/L, ANC ≥1.5×10⁹/L, PLT ≥80×10⁹/L, bilirubin ≤1.5×ULN, ALT/AST ≤2.5×ULN (≤5×ULN if liver mets), Cr ≤1×ULN.

Patients with advanced SGC were stratified into four arms based on genetic subtypes. This analysis focuses on Arm 1 (HER2 overexpression: IHC 3+ or IHC 2+/ISH+) and Arm 4 (HER2-low: IHC 1+ or IHC 2+/ISH-). In Arm 1, patients received SHR-A1811 at 4.8 mg/kg IV on Day 1 of a 21-day cycle. In Arm 4, patients received 4.8 mg/kg or 5.6 mg/kg (if tolerated).

Key secondary endpoints include disease control rate (DCR: CR/PR/SD per RECIST 1.0, same assessment schedule), progression-free survival (PFS: time to progression/death, RECIST v1.1, up to 2 years), overall survival (OS: time to death, up to 2 years), and adverse events (hematologic/non-hematologic per CTCAE 5.0, monitored from consent to 30 days post-last cycle).

Eligible patients (females aged 18-75) have treatment-naive HER2+ stage II-III breast cancer (ECOG 0-1). Exclusions: prior antitumor therapy, bilateral/Stage IV disease, malignancies in 5 years (exceptions: cured CIS/skin cancer), drug absorption issues, recent trial participation, significant organ dysfunction (cardiac/pulmonary/liver), or drug allergies.

Eligible women aged 18-75 with newly diagnosed stage II-III, untreated HER2+ BC received SHR-A1811 Q3W and daily pyrotinib for six cycles. Initial treatment was SHR-A1811 at 4.8 mg/kg and pyrotinib at 240 mg/day (Cohort A). Dose adjustments followed the 3+3 principle: If tolerated, SHR-A1811 could escalate to 5.6 mg/kg, maintaining pyrotinib (Cohort B). For intolerance or investigator discretion, adjustments included SHR-A1811 at 4.8 mg/kg with pyrotinib at 160 mg/day (Cohort C), or SHR-A1811 at 4.0 mg/kg with pyrotinib at 240 mg/day (Cohort D).

Eligible patients must have advanced/metastatic gastric/GEJ adenocarcinoma or colorectal cancer (refractory to standard therapy) with ≥1 measurable lesion (RECIST 1.1), ECOG 0-1, life expectancy ≥3 months, and adequate organ function. Exclusions: unresolved Grade >1 toxicities, prior HER2-ADC exposure, symptomatic CNS/meningeal metastases, or active infections requiring systemic treatment.

Phase 1 evaluates safety/tolerability of SHR-A1811 through incidence/severity of AEs (CTCAE v5.0; monitored Day1-90 post-last dose, ~3 years), MTD determination (DLTs in first 21-day cycle), and RP2D selection (based on safety/PK/efficacy over 12 months). Phase 2 primary endpoint is ORR (RECIST v1.1, IRC-assessed, tumor imaging q6w→q12w post-54w until progression/new therapy/death, ~3 years).

Eligible patients (18-75 years, ECOG 0-1, life expectancy ≥12 weeks) must have histologically confirmed locally advanced/metastatic salivary gland carcinoma: Arm 1 (HER2-altered), Arm 2 (AR-positive), Arm 3 (HER2/AR-negative), or Arm 4 (low HER2 expression), with ≥1 measurable lesion (RECIST v1.1). Key exclusions: active malignancies (5 years), recent antitumor therapy (28 days prior, or <5 half-lives), uncontrolled cardiac conditions (NYHA ≥II, LVEF <50%, QTc >450ms♂/470ms♀), uncontrolled hypertension, gastrointestinal absorption issues (Arm 2), bleeding risks, or abnormal coagulation (INR/aPTT >1.5×ULN). Organ function thresholds: HB ≥90g/L, ANC ≥1.5×10⁹/L, PLT ≥80×10⁹/L, bilirubin ≤1.5×ULN, ALT/AST ≤2.5×ULN (≤5×ULN if liver mets), Cr ≤1×ULN.

Patients with advanced SGC were stratified into four arms based on genetic subtypes. This analysis focuses on Arm 1 (HER2 overexpression: IHC 3+ or IHC 2+/ISH+) and Arm 4 (HER2-low: IHC 1+ or IHC 2+/ISH-). In Arm 1, patients received SHR-A1811 at 4.8 mg/kg IV on Day 1 of a 21-day cycle. In Arm 4, patients received 4.8 mg/kg or 5.6 mg/kg (if tolerated).

Key secondary endpoints include disease control rate (DCR: CR/PR/SD per RECIST 1.0, same assessment schedule), progression-free survival (PFS: time to progression/death, RECIST v1.1, up to 2 years), overall survival (OS: time to death, up to 2 years), and adverse events (hematologic/non-hematologic per CTCAE 5.0, monitored from consent to 30 days post-last cycle).

This study evaluates the pathological complete response rate (pCR) as the primary endpoint within 24 weeks, while secondary endpoints include three-year invasive disease-free survival (iDFS), overall response rate (ORR), adverse effects using CTCAE v4.0, gene expression profiling via RNA-seq, and peripheral blood mononuclear cell (PBMC) counts measured by flow cytometry throughout the treatment period.

Eligible participants must have histologically confirmed stage II-III invasive breast cancer (T2N0-1/T3N0 for stage II; T2N2/T3N1-2 for stage III), aged 18-70, ECOG 0-1, with confirmed ER/PR/HER2 status, LVEF ≥55%, and proper subtyping (SNF or triple-negative based on AR/CD8/FOXC1). Acceptable organ function is required (HB≥90g/L, ANC≥1500/uL, platelets≥75K/uL, bilirubin≤1.5xULN, AST/ALT≤3xULN, creatinine clearance>50mL/min). Fertile women must use contraceptives during and 3 months post-study.

Eligible patients must have unresectable/metastatic HER2+ breast cancer (prior trastuzumab + taxane treatment), ECOG 0-1, measurable disease (RECIST v1.1), and adequate organ function. Exclusions: uncontrolled effusions, recent antitumor therapy (≤4 weeks for chemo/immunotherapy, ≤2 weeks for endocrine), active autoimmune/cardiac disease (NYHA ≥II), HIV/HBV/HCV infection, unresolved toxicity (>CTCAE Gr1), or severe allergies to monoclonal antibodies. WOCBP must use contraception for 7 months post-treatment.

Eligible patients have HR+/HER2-low (IHC 1+ or 2+/ISH-) metastatic breast cancer with 0-1 prior chemotherapy lines in the metastatic setting, measurable lesions, and adequate organ function. Key exclusions: active CNS metastases (unless stable treated), HIV/autoimmune disease, ILD/pneumonitis history, significant CVD, active HBV/HCV infection, or prior malignancies (except low-risk) within 5 years.

Eligible patients have ECOG 0-1, HER2 IHC 0 advanced/metastatic breast cancer (never HER2+), measurable lesions (RECIST 1.1), and progression after ≥1 chemotherapy line (HR+ tumors require prior endocrine therapy). Exclusions: prior anti-HER2 therapy, recent treatments (surgery/RT/systemic therapies within 4w; endocrine therapy within 2w), active CNS metastasis, immunosuppression (>10mg/day prednisone), uncontrolled comorbidities, HIV/HBV/HCV infection, or other malignancies (except cured skin/CIS) within 5 years.

Eligible are women aged 18-75 with HER2-low metastatic breast cancer (ECOG 0-1), measurable lesions, and ≥12-week life expectancy. Exclusions: recent treatments/procedures (within 4 weeks), other cancers (last 5 years), significant comorbidities (cardiac/hepatic diseases), drug allergies, or conditions affecting absorption. WOCBP must use contraception.

Eligible female patients (18-75 years) have HER2+ (IHC3+/ISH+) unresectable/metastatic breast cancer (ECOG 0-1, ≥12-week life expectancy, measurable lesions per RECIST v1.1, adequate organ function). Exclusions: recent malignancies (past 5 years), untreated CNS metastases, early recurrence (<12 months post- (neo)adjuvant therapy), uncontrolled effusions, recent anti-tumor treatments (4 weeks prior), immunodeficiency, severe cardiovascular/interstitial lung disease, unresolved toxicity (>Grade 1), bleeding disorders, active hepatitis/cirrhosis, or other clinically significant comorbidities.

Eligible participants are women (18-75 years) with HER2+ invasive breast cancer (pre-neoadjuvant stage T1-4/N0-3/M0, excluding T1N0) and residual disease post-surgery/neoadjuvant therapy (≥9 weeks taxane + trastuzumab). Exclusions: metastatic/recurrent disease, prior HER2-ADC exposure, high anthracycline doses (>240mg/m2 doxorubicin or >480mg/m2 epirubicin), significant cardiovascular/respiratory disorders, hepatitis/liver cirrhosis, or conditions increasing study risk. HR status and ECOG 0-1 are required.

Eligible females (18-75 years, ECOG 0-1) have confirmed metastatic/locally advanced breast cancer (ER+/HER2± or TNBC) with measurable lesions (RECIST v1.1) and organ function. Exclusions: uncontrolled brain metastases, active lung/cardiovascular diseases, recent immunosuppression, unresolved treatment toxicity (>Grade 1), active infections/hepatitis, prior malignancies (5 years), autoimmune/immunodeficiency disorders, or severe allergies to study drugs.

Eligible patients are treatment-naive women aged 18-75 with HR+/HER2-low stage II-III breast cancer, ECOG 0-1, and adequate organ function. Exclusions include prior anti-tumor therapy, stage IV disease, concurrent malignancies, significant comorbidities (cardiovascular, lung, liver, or psychiatric disorders), and participation in other trials within 4 weeks.

Secondary endpoints include breast pathological complete response (bpCR: ypT0-is), residual cancer burden (RCB), best overall response rate (BORR) during neoadjuvant treatment, and long-term survival outcomes (OS, DFS, EFS) over 5 years. Health-related quality of life (HRQOL) is evaluated using EORTC QLQ-C30 and QLQ-BR23 during the 18-week neoadjuvant phase.

Eligible patients were ≥18 years with HER2+ breast cancer and measurable untreated intracranial lesions (RANO-BM criteria), ≥2 weeks post-systemic therapy, and adequate organ function. Exclusions included prior DS-8201a/ADC therapy, recent trial participation, severe comorbidities (lung disease, uncontrolled hypertension/diabetes), or other safety risks per investigator judgment.

The primary endpoint is Overall Response Rate (ORR), assessed every 6 weeks from randomization until first documented progression or death, whichever occurs first, up to 3 years. Secondary endpoints include 3-month Progression-Free Survival (PFS) rate, PFS assessed similarly up to 3 years, Clinical Benefit Rate (CBR), and safety endpoints (incidence of AEs, SAEs, and irAEs).

Eligible participants must be ≥18 years old with ER/PgR ≤10% and low HER2 expression, advanced breast cancer, prior taxane/anthracycline therapy, RECIST 1.1 measurable lesions, ECOG PS 0-1, and adequate organ function. Exclusions include active CNS metastases, prior anti-HER2 ADC treatment, active autoimmune disease, immunosuppressant use, other malignancies, severe ADC-related toxicities, uncontrolled cardiac conditions, active infections, live vaccine receipt within 4 weeks, or psychiatric/substance abuse issues.

The primary endpoint is Objective Response Rate (ORR) by investigator assessment, defined as the percentage of evaluable patients achieving CR or PR per RECIST v1.1, measured from randomization until first progression or death, up to 3.5 years. Secondary endpoints include Disease Control Rate (DCR: CR/PR/SD), Clinical Benefit Rate (CBR: CR/PR/SD≥24 weeks), Duration of Response (DoR), Progression-Free Survival (PFS), Overall Survival (OS), and safety (AE incidence).

Eligible patients are females aged 18-75 with HER2-negative advanced breast cancer, ECOG PS 0-1, prior 1-2 lines of systemic therapy (CDK4/6 inhibitor required if HR-positive), ≥1 measurable lesion per RECIST v1.1, stable brain metastases if present, no prior PD- (L)1 inhibitors, and adequate organ function. Exclusion criteria include active/uncontrolled brain metastases, prior anti-HER2/TROP-2 therapy, unresolved third-space fluid, recent antitumor treatments, active autoimmune/immunodeficiency disorders, HBV/HCV infection, immunosuppressant use, second malignancies, or hypersensitivity to study drugs.

Eligible patients are female, aged 18-75, ECOG 0-1, with stage II/III HR-negative/low HER2+ breast cancer (tumor >2 cm), adequate organ function, and contraception compliance. Exclusions include metastatic/inflammatory breast cancer, prior malignancy (except certain carcinomas), interstitial lung disease, severe CVD, uncontrolled infections, bleeding disorders, or recent anticancer therapies.

Additional exclusions include recent chemo/radiotherapy (within 3 weeks), uncontrolled effusions, unresolved grade ≥1 toxicities (excluding alopecia), steroid use (>10mg/day prednisone-equivalent), or conditions deemed high-risk by investigators. Fertile females must use contraception during and for 3 months post-treatment. All participants must provide informed consent and comply with follow-up.

Eligible patients are ≥18 with locally advanced/metastatic breast cancer, prior ADC exposure, measurable disease, and adequate organ function (HB ≥90 g/L, ANC ≥1.5x10^9/L, ALT/AST ≤3-5×ULN, LVEF ≥50%). Key exclusions: uncontrolled CNS metastases, significant heart disease, active HBV/HCV/HIV, recent immunosuppressants, autoimmune diseases, major surgery within 3 weeks, pregnancy/lactation, or other malignancies (except non-melanoma skin/cervical carcinoma in situ).

Key inclusion criteria include age >18, ECOG PS 0-2, life expectancy ≥3 months, measurable brain metastases (no prior radiotherapy), stable mannitol/hormone use, adequate organ function, and recovery from prior treatment toxicities (≤G1). Exclusions cover leptomeningeal/cystic metastases, uncontrolled third-space fluid, emergent CNS complications, recent radiotherapy/chemotherapy, unresolved lung disease, bleeding risks, active infections, and significant cardiac/HTN conditions.

Eligible patients are females aged 18-75 with ECOG 0-2, locally advanced/metastatic breast cancer, no prior systemic therapy, and adequate organ function. Exclusions include uncontrolled diabetes, active infections, prior malignancies (except cured cases), severe comorbidities, pregnancy, or conditions compromising study adherence per investigator judgment.

Eligible participants (age 18-75, ECOG 0-1) must have advanced pancreatic cancer with measurable lesions; exclusions include active infections, untreated CNS metastases, uncontrolled comorbidities, recent major surgery, or immunodeficiencies (e.g., HIV, active hepatitis B/C). High pancreatitis risk, recent immunotherapies, or unresolved treatment toxicity also disqualify participation per investigator assessment.

Eligible patients are HR+/HER2- advanced breast cancer females (≥18 years) with prior CDK4/6 inhibitor exposure, measurable lesions, and adequate organ function. Exclusions include recent anticancer therapies (except bisphosphonates), uncontrolled CNS/heart disease, persistent toxicities (≥Grade 1), major surgery within 3 weeks, pregnancy, or other malignancies (except cured non-melanoma skin/cervical cancers) in 5 years.

Eligible patients (18-75 years, ECOG 0-1) must have unresectable/metastatic biliary tract cancer, ≥1 measurable lesion, adequate organ function, and HBV-DNA <500 IU/mL if HBV+. Exclusions cover recent anticancer therapies (<4 weeks), CNS metastases, severe comorbidities (cardiac/hepatic/pancreatic disorders, uncontrolled effusions), active infections, or thromboembolic events within 6 months.

Eligible patients (18-75 years, ECOG 0-1) must have newly diagnosed locally advanced/metastatic biliary tract cancer with ≥1 measurable lesion and adequate organ function. Key exclusions: concurrent malignancies, recent local therapy (<4 weeks), biliary obstruction, active autoimmune/interstitial lung diseases, uncontrolled HBV, or severe cardiovascular conditions.

Eligible patients must have RAS/RAF wild-type metastatic colorectal cancer (post-oxaliplatin/5-FU/irinotecan ± anti-PD-1/PD-L1 failure for DMMR/MSI-H), ≥1 measurable lesion (RECIST 1.1), ECOG 0-1, and adequate organ function. Exclusions: active infections (HBV DNA ≥500 IU/mL, HCV+), uncontrolled effusions, recent major surgery/immunosuppressants (>10 mg prednisone/day), CNS metastases, or other malignancies within 5 years (excl. non-melanoma skin/cervical carcinoma in situ).

Eligible participants (18-75 years, ECOG 0-1, life expectancy >3 months) must have histologically confirmed unresectable/metastatic gastric/GEJ adenocarcinoma (Cohorts A/B) with ≥1 measurable lesion (RECIST 1.1) and adequate organ function (ANC ≥1.5×10⁹/L, PLT ≥100×10⁹/L, LVEF ≥50%, etc.). Exclusions: untreated/active CNS metastases, uncontrolled effusions, prior topoisomerase I inhibitor ADC therapy (e.g., DS-8201), immunosuppressants (>10 mg/day prednisone within 14 days), unresolved Grade >1 toxicities (excluding alopecia), active HBV/HCV infection, severe cardiovascular disease, or uncontrolled infections (IV antibiotics within 2 weeks).

Eligible patients (18-75 years, ECOG 0-1, HER2+, life expectancy ≥3 months) must have locally advanced/metastatic gastric/GEJ adenocarcinoma-Phase Ib: prior treatment failure/intolerance; Phase II: treatment-naïve. Exclusions: uncontrolled effusions, recent major surgery (4 weeks), active autoimmunity, interstitial pneumonia, recent severe infection (4 weeks), tuberculosis (1 year), cardiovascular risks, or recent GI perforation/fistula (6 months).

Eligible patients (18-75 years, ECOG 0-1) must have metastatic NSCLC, measurable lesions, organ function adequacy, and failed standard therapy. Exclusions involve active CNS metastases, recent antitumor therapies, uncontrolled comorbidities, autoimmune/cardiac diseases, infections, pregnancy, or conditions affecting drug absorption/compliance per investigator judgment. Tissue samples are mandatory.

Eligible patients (18-75 years, ECOG 0-1) must have HER2-mutated advanced/metastatic NSCLC without prior systemic treatment, measurable lesions (RECIST 1.1), and adequate organ function. Exclusions include mixed histology, additional driver mutations (with approved targeted drugs), untreated CNS metastases, uncontrolled pain, concurrent malignancies, interstitial pneumonia, autoimmune/cardiovascular diseases, or active hepatitis B/C.

Eligible participants must provide informed consent, supply tumor tissue for testing, have measurable lesions per RECIST v1.1, an ECOG PS of 0-1, and expected survival ≥12 weeks. Key exclusions involve uncontrolled CNS metastases, symptomatic effusions, interstitial lung disease, poorly managed hypertension, serious infections, immune deficiency, or other factors compromising study integrity.

Secondary endpoints include duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and standard response rate (RR), all monitored every 9 weeks for about one year. Overall survival (OS) is tracked for around 3 years post-enrollment, while adverse events (AEs) and serious adverse events (SAEs) are recorded from first dose to 90 days post-treatment.

Eligible patients must be ≥18 years old with measurable lesions per RECIST 1.1, ECOG 0-1, life expectancy ≥12 weeks, and adequate organ function. Exclusions include untreated brain/meningeal metastases, symptomatic effusions requiring drainage, prior malignancies (within 5 years), uncontrolled cardiovascular/autoimmune diseases, active hepatitis, unresolved treatment-related toxicities (CTCAE >1), and recent GI obstruction/perforation.

Secondary endpoints include duration of response (DoR), disease control rate (DCR), time to recovery (TTR), progression-free survival (PFS), and overall survival (OS) up to 100 months, along with 12-month survival rate. Safety endpoints track AEs/SAEs per CTCAE v5.0 and dose modifications due to toxicity. Pharmacokinetics (PK) parameters (Cmin, C3h, Cmax, AUC0-t) and immunogenicity (ADA, NAb) of SHR-A1811 and Fluzoparib are monitored over defined periods.

Eligibility requires age 18-75, ECOG 0-1, HER2-positive advanced/metastatic solid tumors, measurable lesions, and adequate organ function. Key exclusions include active CNS/meningeal metastases, prior HER2 ADC/ TKI use, unresolved toxicities >CTCAE G2, active ILD, uncontrolled infections (HBV/HCV/HIV), recent major surgery, allergies to study drugs, pregnancy, or uncontrolled comorbidities (e.g., hypertension, thrombosis risk). Part B1 further excludes G2+ neuropathy or BP102-related bleeding/thrombosis risks.

Eligible patients (18-75 years, ECOG 0-1, CLDN18.2-positive, measurable lesions) must have adequate organ function; exclusions include recent antitumor therapy, active infections, severe comorbidities (cardiovascular/autoimmune diseases, hepatitis/HIV), unresolved toxicities (>Grade 1), or gastrointestinal complications (e.g., perforation, bleeding).

Eligible patients (≥18 years, ECOG 0-1, life expectancy ≥3 months) must have advanced/metastatic solid tumors failing standard therapy with measurable lesions. Exclusions include recent antitumor treatments (within 4 weeks), active CNS metastases, uncontrolled infections (HBV/HCV/HIV), significant comorbidities, or unresolved toxicities (>Grade 1).

Eligible patients (≥18 years, ECOG 0-1, life expectancy ≥3 months) must have advanced/metastatic solid tumors failing standard therapy with measurable lesions. Exclusions include recent antitumor treatments (within 4 weeks), active CNS metastases, uncontrolled infections (HBV/HCV/HIV), significant comorbidities, or unresolved toxicities (>Grade 1).

Eligible participants are ≥18 years with locally advanced/recurrent metastatic breast cancer (HR+/HER2- or triple-negative), prior ADC exposure, and measurable disease (RECIST 1.1). Required organ function: HB ≥90 g/L, ANC ≥1.5×10⁹/L, ALT/AST ≤3×ULN (≤5×ULN with liver mets), LVEF ≥50%. Exclusions: uncontrolled CNS metastases, active HBV/HCV/HIV, major surgery/immunotherapy within 3 weeks, third-space effusions, or pregnancy. Prior endocrine therapy (including CDK4/6 inhibitors) requires ≥14-day washout.

Efficacy measures include progression-free survival (PFS; time to progression/death), clinical benefit rate (CBR; CR+PR+SD ≥24 weeks), and duration of response (DOR; sustained until progression/death)-all monitored for 36 months alongside treatment-related toxicity (CTCAE v5.0). Overall survival (OS) is tracked for 5 years, with censoring for surviving participants.

Eligible participants are female ≥18 years with untreated triple-negative breast cancer (TNBC) confirmed histologically, measurable lesions (RECIST 1.1), and ECOG 0-1. Key exclusions: prior anti-cancer therapy (chemotherapy/immunotherapy), active HBV/HCV, autoimmune/cardiovascular diseases, concurrent malignancies, or pregnancy. Organ function requirements: adequate bone marrow/hepatic reserves. Surgical recovery must be complete if applicable.

Eligible participants are 18-75 years, with advanced/metastatic pancreatic cancer (RECIST v1.1 measurable lesions) after standard treatment failure and ECOG 0-1. Exclusions: active CNS metastases, untreated HBV/HCV/HIV, recent major surgery, severe cardiovascular/thromboembolic events, or uncontrolled infections/autoimmune diseases. Key requirements: adequate organ function, negative pregnancy test, and contraception use.

Eligible patients are HR+/HER2- advanced breast cancer patients (ER/PR >10%+, HER2 non-amplified) with prior CDK4/6 inhibitor exposure, measurable lesions (RECIST 1.1), and adequate organ function (ANC ≥1.5x10⁹/L, platelets ≥75x10⁹/L, ALT/AST ≤3×ULN, Cr ≤1×ULN). Exclusions: uncontrolled CNS metastases, recent major surgery/chemotherapy (within 3 weeks), active cardiac disease, pregnancy, or other malignancies (past 5 years). Fertile patients must use contraception.

Eligible patients are 18-70 years with locally advanced/metastatic esophageal squamous cell carcinoma (RECIST 1.1 measurable lesions), ECOG 0-1, and adequate organ function. Exclusions: uncontrolled CNS metastases, active hepatitis B/C, recent major surgery/radiotherapy (within 4 weeks), gastrointestinal perforation/fistula (≤6 months), or prior topoisomerase I inhibitor ADCs. Fertile subjects must use contraception. Other exclusions: severe cardiovascular disease, thrombosis (≤3 months), unresolved toxicity (>Grade 1), or live vaccines (≤28 days).

The recommended Phase II dose (RP2D) will be determined based on safety, PK, and efficacy data during Phase IB (~1 year). Adverse events (AEs; NCI-CTCAE v5.0) and dose-limiting toxicities (DLTs) are monitored from Day 1 to 90 days post-last dose, while ORR (RECIST 1.1) is assessed every 6 weeks (≤48 weeks) and every 9 weeks thereafter, up to 18 months post-enrollment.

Eligible patients have recurrent/metastatic gynecological malignancies (RECIST 1.1 measurable), ECOG 0-1, and adequate organ function. Exclusions: active brain metastases, prior topoisomerase I inhibitor ADCs, major surgery within 28 days, active HBV/HCV/HIV, pulmonary tuberculosis (≤1 year), or SHR-A2102 hypersensitivity. Fertile females must use effective contraception for ≥7 months post-treatment.

Secondary efficacy measures include duration of response (DoR), disease control rate (DCR), time to response (TTR), and progression-free survival (PFS), all assessed via RECIST 1.1 at the same imaging intervals. Overall survival (OS) will be tracked every 60 days for up to 36 months, alongside 12-month survival rate. Safety will monitor AEs (NCI-CTCAE v5.0), while pharmacokinetic (PK) traits (plasma concentrations of SHR-A2102/metabolites) and immunogenicity (ADA/Nab levels) will be analyzed over 24 months.

Eligible subjects aged 18-70 must consent, provide tumor tissue, have measurable NSCLC (squamous), ECOG 0-1, ≥12-week life expectancy, and adequate organ function. Exclusions include active brain metastases, other malignancies (except certain cured cases), uncontrolled effusions/pain, recent anticancer treatments/radiotherapy/surgery, unresolved toxicities (>CTCAE1), immunosuppressive/autoimmune conditions, severe infections/CVD, hepatitis B/C, TB, bleeding risks, immunodeficiency, pregnancy, mental illness, or other investigator-judged risks.

The RP2D will be determined based on safety, PK, and efficacy data from Phase IB over approximately 1 year. AE incidence and severity (including DLTs) will be assessed per NCI-CTCAE v5.0 from Day 1 to 90 days post-last dose. ORR will be evaluated every 6 weeks for 48 weeks, then every 9 weeks for up to 18 months post-enrollment, using RECIST1.1 criteria.

Eligible patients (≥18 years, ECOG 0-1, life expectancy ≥12 weeks) must have locally advanced/metastatic solid tumors (failed standard therapy for Phase IB, untreated for Phase II) with measurable lesions. Key exclusions include active CNS metastases, prior topoisomerase I inhibitor ADC/PD-1/PD-L1 therapy (Phase II), recent antitumor treatment (within 4 weeks), unresolved toxicities (>Grade 1), active infections (HBV/HCV/TB), autoimmune diseases, or uncontrolled comorbidities. Pregnancy, recent live vaccines, major surgery (within 28 days), or severe allergies to study drugs also preclude participation.

Eligible patients (≥18 years, ECOG 0-1) must have histologically confirmed advanced urothelial carcinoma (treatment-experienced for Phase Ib, treatment-naive for Phase II) with measurable lesions. Key exclusions include active CNS metastases, prior TOPO1-ADC treatment, recent anticancer therapy (<4 weeks), unresolved toxicities (>Grade 1), uncontrolled autoimmune diseases, or significant cardiac/pulmonary complications.

Eligible participants must be aged 18-80 with ECOG 0-1, confirmed advanced/metastatic urothelial carcinoma post-platinum/PD- (L)1 therapy, and measurable lesions per RECIST v1.1. Exclusions involve recent anti-tumor treatments, prior topoisomerase I ADC exposure, uncontrolled CNS metastases, active infections, significant comorbidities, or pregnancy. Organ function and contraception compliance are required.

Eligible patients have histologically confirmed advanced/metastatic solid tumors refractory to standard therapy, ≥1 measurable lesion (RECIST v1.1), ECOG 0-1, life expectancy ≥12 weeks, and adequate organ function. Exclusions include active CNS metastases, recent antitumor therapy (≤4 weeks), prior topoisomerase-I ADC treatment, severe CV/cerebrovascular disease, recent infection (≤4 weeks), or unresolved prior treatment toxicities (Grade >1).

Eligible participants are women (18-75) with metastatic/locally advanced breast cancer (ER+/HER2± or TNBC), ECOG 0-1, measurable lesions per RECIST v1.1, and adequate organ function. Exclusions include active CNS metastases, uncontrolled infections, severe cardiovascular/autoimmune diseases, recent immunosuppression, untreated hepatitis, concurrent malignancies, HIV/organ transplant history, or drug component allergies.

Eligible participants are adults (≥18) with locally advanced/metastatic breast cancer (any HR status) who received prior ADCs and CDK4/6 inhibitors (HR+), have measurable disease (RECIST 1.1), and adequate organ function. Exclusions include active CNS metastases, uncontrolled HBV/HCV/HIV, recent immunosuppression/therapy (≤3 weeks), severe cardiac disease, autoimmune disorders, or pregnancy. Lab criteria require ANC≥1.5×10^9/L, PLT≥75×10^9/L, and LVEF≥50%.

Eligible participants are women ≥18 with HR+/HER2- locally advanced/metastatic breast cancer (ER/PR>10%, HER2 0-1+/FISH-negative) who failed CDK4/6 inhibitors, have measurable lesions (RECIST 1.1), adequate organ function (ANC≥1.5×10⁹/L, Cr≤1×ULN), and ECOG≤2. Exclusions include active CNS metastases, recent cardiac events (≤6 months), major surgery/therapy (≤3 weeks), pregnancy, or other malignancies (≤5 years). Contraception is required for 3 months post-treatment.

Eligible patients are adults (18-75) with locally advanced/unresectable or metastatic ESCC who progressed after first-line chemo/immunotherapy (PFS≥3 months if prior IO), have measurable lesions (RECIST 1.1), ECOG 0-1, adequate organ function (ANC≥1.5×10⁹/L, LVEF≥50%), and tissue for biomarker analysis. Key exclusions: active autoimmune disease, uncontrolled infections (HBV/HCV), recent bleeding/thrombosis, CNS metastases, immunosuppressant use (>10mg/day prednisone), pregnancy, or other malignancies (≤5 years). Contraception required for 6 months post-treatment.

Eligible patients (18-75 years) must have metastatic NSCLC (AJCC 8th edition), progressed post standard and ADC therapy, ≥1 measurable lesion per RECIST 1.1, ECOG 0-1, life expectancy ≥12 weeks, adequate organ function, and contraceptive agreement. Exclusions: untreated brain/meningeal metastases, symptomatic malignant effusions, prior systemic therapy, major surgery/radiotherapy (≤4 weeks), second malignancies, active hepatitis/TB, uncontrolled hypertension, unresolved toxicities, severe prior hypersensitivity, or other conditions that may compromise study integrity.

Eligible patients are aged 18-75 with unresectable/metastatic non-squamous NSCLC, prior EGFR-TKI failure, ≥1 measurable lesion (RECIST v1.1), ECOG 0-1, life expectancy ≥12 weeks, and adequate organ function. Exclusions: active CNS metastases, recent antitumor therapy or major surgery (≤4 weeks), other malignancies (≤5 years), interstitial lung disease, severe cardiovascular disorders, active infections (≤4 weeks), recent thrombosis (≤3 months), HIV/hepatitis B/C, or hypersensitivity to study drugs.

Eligible patients (18-75 years) must have histologically confirmed advanced/metastatic solid tumors, ≥1 measurable lesion (RECIST v1.1), ECOG 0-1, life expectancy ≥12 weeks, and adequate organ function. Exclusions: active CNS metastases, untreated spinal compression, uncontrolled pain/effusions, recent antitumor therapy/radiotherapy/surgery (≤4 weeks), secondary malignancies (≤3 years), interstitial lung disease, severe cardiocerebrovascular conditions, recent bleeding (≤3 months), HIV/hepatitis B/C, drug allergies, substance dependence, or psychiatric/pregnancy-related contraindications.

Eligible patients must have confirmed metastatic/refractory solid tumors with ≥1 measurable lesion (RECIST 1.1), ECOG 0-1, life expectancy ≥12 weeks, and adequate organ function. Exclusions include active CNS metastases, recent antitumor therapy (≤4 weeks), prior topoisomerase-I ADC use, severe cardiovascular conditions, recent severe infections (≤4 weeks), or unresolved treatment-related toxicities (Grade>1).

Eligible patients (18-75 years) have confirmed advanced/metastatic NSCLC, ≥1 measurable lesion (RECIST 1.1), ECOG 0-1, and adequate organ function. Exclusions: active CNS metastases, unresolved spinal cord compression, recent antitumor therapy (≤4 weeks), major surgery/trauma (≤4 weeks), untreated autoimmune diseases, severe infections (≤4 weeks), HBV/HIV positivity, or prior severe allergic reactions to monoclonal antibodies or SHR-A2009 components.

Eligible patients (≥18 years) must have histologically confirmed advanced/metastatic solid tumors refractory to standard therapy, ≥1 measurable lesion (RECIST 1.1), ECOG 0-1, and ≥12-week life expectancy. Key exclusions include prior B7-H3 therapy, recent anticancer treatments (chemotherapy/radiation/monoclonal antibodies within 2-4 weeks), major surgery within 4 weeks, uncontrolled comorbidities, active infections (antibiotics within 2 weeks), pregnancy, or HS-20093 component hypersensitivity. Contraception is mandatory for fertile participants.

This phase I study consists of two stages: the dose-escalation stage (Ia) aims to determine the maximum tolerated dose (MTD) of intravenous HS-20093 in advanced solid tumor patients within the first 21-day cycle; the dose-expansion stage (Ib) evaluates investigator-assessed objective response rate (ORR) by RECIST 1.1 (confirmed CR/PR requiring ≥4-week interval imaging) from first dose until progression or withdrawal (24-month maximum).

Primary safety endpoints include AE incidence/severity (CTCAE v5.0) monitored from first dose to 90 days post-treatment. Pharmacokinetic parameters (Cmax, Tmax, T1/2, AUC0-t) and anti-drug antibodies (up to 90 days post-treatment) will be assessed during Cycle 1. Secondary efficacy measures include ORR (dose-escalation), duration of response (DOR), disease control rate (DCR; requiring ≥5-week SD confirmation), progression-free survival (PFS), and overall survival (OS; dose-expansion only), all evaluated per RECIST 1.1 over 24 months.

Eligible patients (≥18 years) must have histologically confirmed advanced/metastatic solid tumors refractory to standard therapy, ≥1 measurable lesion (RECIST 1.1), ECOG 0-1, and ≥12-week life expectancy. Key exclusions include prior B7-H3 therapy, recent anticancer treatments (chemotherapy/radiation/monoclonal antibodies within 2-4 weeks), major surgery within 4 weeks, uncontrolled comorbidities, active infections (antibiotics within 2 weeks), pregnancy, or HS-20093 component hypersensitivity. Contraception is mandatory for fertile participants.

This phase I study consists of two stages: the dose-escalation stage (Ia) aims to determine the maximum tolerated dose (MTD) of intravenous HS-20093 in advanced solid tumor patients within the first 21-day cycle; the dose-expansion stage (Ib) evaluates investigator-assessed objective response rate (ORR) by RECIST 1.1 (confirmed CR/PR requiring ≥4-week interval imaging) from first dose until progression or withdrawal (24-month maximum).

Primary safety endpoints include AE incidence/severity (CTCAE v5.0) monitored from first dose to 90 days post-treatment. Pharmacokinetic parameters (Cmax, Tmax, T1/2, AUC0-t) and anti-drug antibodies (up to 90 days post-treatment) will be assessed during Cycle 1. Secondary efficacy measures include ORR (dose-escalation), duration of response (DOR), disease control rate (DCR; requiring ≥5-week SD confirmation), progression-free survival (PFS), and overall survival (OS; dose-expansion only), all evaluated per RECIST 1.1 over 24 months.

Eligible patients (≥18 years) must have metastatic sarcomas refractory to first-line therapy, ≥1 measurable lesion (RECIST 1.1), ECOG 0-1, and ≥12-week life expectancy. Key exclusions include prior B7-H3 therapy, recent cancer treatments (chemotherapy/radiotherapy/antibodies within 2-4 weeks), uncontrolled metastases/comorbidities, Grade >2 toxicities (except alopecia/neurotoxicity), active infections (HBV/HCV/HIV), CYP3A4-modifying drugs, or conditions compromising safety. Fertile participants must use contraception; pregnancy is prohibited.

Safety assessments include AE incidence/severity (CTCAE v5.0) from first dose through 90 days post-treatment. PK parameters (Cmax, Tmax, T1/2, AUC0-t) will be measured during Cycle 1 (21-day cycle). Immunogenicity will assess anti-drug antibodies up to 90 days post-treatment. Secondary efficacy endpoints include IRC-confirmed ORR, duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), 4-month PFS rate, and overall survival (OS) over 24 months.

Eligible patients (≥18 years) must have histologically confirmed advanced/metastatic solid tumors refractory to standard therapy, ≥1 measurable lesion (RECIST 1.1), ECOG 0-1, and ≥12-week life expectancy. Key exclusions include prior B7-H3 therapy, recent anticancer treatments (chemotherapy/radiation/monoclonal antibodies within 2-4 weeks), major surgery within 4 weeks, uncontrolled comorbidities, active infections (antibiotics within 2 weeks), pregnancy, or HS-20093 component hypersensitivity. Contraception is mandatory for fertile participants.

This phase I study consists of two stages: the dose-escalation stage (Ia) aims to determine the maximum tolerated dose (MTD) of intravenous HS-20093 in advanced solid tumor patients within the first 21-day cycle; the dose-expansion stage (Ib) evaluates investigator-assessed objective response rate (ORR) by RECIST 1.1 (confirmed CR/PR requiring ≥4-week interval imaging) from first dose until progression or withdrawal (24-month maximum).

Primary safety endpoints include AE incidence/severity (CTCAE v5.0) monitored from first dose to 90 days post-treatment. Pharmacokinetic parameters (Cmax, Tmax, T1/2, AUC0-t) and anti-drug antibodies (up to 90 days post-treatment) will be assessed during Cycle 1. Secondary efficacy measures include ORR (dose-escalation), duration of response (DOR), disease control rate (DCR; requiring ≥5-week SD confirmation), progression-free survival (PFS), and overall survival (OS; dose-expansion only), all evaluated per RECIST 1.1 over 24 months.

Eligible patients (≥18 years) must have metastatic sarcomas refractory to first-line therapy, ≥1 measurable lesion (RECIST 1.1), ECOG 0-1, and ≥12-week life expectancy. Key exclusions include prior B7-H3 therapy, recent cancer treatments (chemotherapy/radiotherapy/antibodies within 2-4 weeks), uncontrolled metastases/comorbidities, Grade >2 toxicities (except alopecia/neurotoxicity), active infections (HBV/HCV/HIV), CYP3A4-modifying drugs, or conditions compromising safety. Fertile participants must use contraception; pregnancy is prohibited.

Safety assessments include AE incidence/severity (CTCAE v5.0) from first dose through 90 days post-treatment. PK parameters (Cmax, Tmax, T1/2, AUC0-t) will be measured during Cycle 1 (21-day cycle). Immunogenicity will assess anti-drug antibodies up to 90 days post-treatment. Secondary efficacy endpoints include IRC-confirmed ORR, duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), 4-month PFS rate, and overall survival (OS) over 24 months.

Key exclusions include untreated CNS metastases, recent major surgery, strong CYP3A4 modulators, QT-prolonging drugs, uncontrolled comorbidities (diabetes, hypertension), or immunosuppressive conditions. Vaccination within 4 weeks or hypersensitivity to HS-20093 components also disqualify participants. Compliance and investigator-assessed safety risks are additional exclusion factors.

Pharmacokinetic parameters (Cmax, Tmax, T1/2, AUC0-t) and immunogenicity (ADA) are analyzed over 24 months. Patients must have measurable lesions (RECIST 1.1), ECOG 0-1, and life expectancy ≥12 weeks. Prior B7-H3/ADC therapy, recent cytotoxic/radiotherapy, uncontrolled metastases, cardiovascular risks, active infections, or unresolved toxicities (>Grade 2) are exclusions.

Eligible patients (18-75 years) must have histologically confirmed metastatic solid tumors, ≥1 measurable lesion (RECIST v1.1), ECOG 0-1, and life expectancy >12 weeks. Exclusions include prior MET/EGFR-targeted therapy, recent anticancer treatments (cytotoxics/TKIs within 2 weeks; investigational drugs/ADCs within 4 weeks), uncontrolled metastases, cardiovascular diseases, Grade ≥2 unresolved toxicities, or active infections.

The safety and tolerability of HS-20117 combination therapy are evaluated by monitoring treatment-emergent AEs (graded per NCI CTCAE v5.0) from the first dose to 90 days post-treatment. The MTD/MAD is determined within 21 days, with MTD defined as the highest dose where ≤1/6 patients experience DLT and MAD based on PK/PD, safety, or exposure plateau.

Eligible patients (≥18 years) have recurrent/metastatic HNSCC or solid tumors refractory to standard therapy, ≥1 measurable lesion (RECIST 1.1), ECOG 0-1, and life expectancy ≥12 weeks. Key exclusions include prior B7-H3 therapy, recent anticancer treatments (cytotoxics within 14 days; macromolecular agents within 28 days), uncontrolled metastases, Grade ≥2 toxicities, active infections (HBV/HCV/HIV), cardiovascular risks, or steroid dependence. Vaccination within 4 weeks or HS-20093 hypersensitivity also preclude enrollment.

Eligible patients (≥18 years) must have untreated ES-SCLC with ≥1 measurable lesion (RECIST 1.1), ECOG 0-1, and life expectancy ≥12 weeks. Key exclusions include prior B7-H3 therapy, recent radiotherapy/surgery (within 4 weeks), uncontrolled effusions, symptomatic CNS metastases, Grade ≥2 unresolved toxicities, active infections (HBV/HCV/HIV), cardiovascular risks, or concurrent CYP3A4/QT-prolonging drugs. Conditions compromising safety or protocol compliance per investigator judgement also disqualify participants.

The primary efficacy endpoint is ORR (confirmed CR/PR requiring ≥4-week confirmation per RECIST 1.1), assessed by investigators over 18 months. Secondary endpoints include DCR (CR+PR+SD), DoR (time from initial response to progression/death), PFS (time to progression/death), and OS (time to death), all evaluated through imaging comparison to baseline tumor burden during the 18-month study period.

Safety assessments monitor AEs (graded by CTCAE v5.0) until 90 days post-treatment. PK analysis includes Cmax, Tmax, T1/2 and AUC0-t measured during Cycle 1 (21 days), alongside immunogenicity (ADA detection). Objective tumor responses are tracked via serial imaging relative to baseline measurements, with SD requiring ≥5 weeks of stability after treatment initiation.

Eligible patients (≥18 years) must have confirmed SCLC that progressed after first-line platinum therapy, ≥1 measurable lesion (RECIST 1.1), ECOG 0-1, and >12-week life expectancy. Critical exclusions include: combined SCLC history, ≤30-day chemotherapy-free interval, prior B7-H3/topotecan treatment, untreated brain metastases, unresolved toxicities (>CTCAE grade 1), significant cardiorespiratory diseases, active infections, or conditions compromising protocol compliance. Fertile patients must use contraception, with pregnancy/breastfeeding excluded.

The primary efficacy endpoint is overall survival (OS), measured from randomization to death from any cause over approximately 4.5 years. Key secondary endpoints include confirmed objective response rate (ORR, CR+PR), disease control rate (DCR, CR+PR+SD), duration of response (DoR), and progression-free survival (PFS), all assessed by blinded independent central review and investigators per RECIST v1.1 through the same 4.5-year timeframe.

Safety evaluations focus on treatment-emergent adverse events (TEAEs) graded by NCI CTCAE v5.0, monitored from first dose through safety follow-up (approximately 4.5 years). Tumor response assessments include: ORR requiring confirmation (CR/PR), DCR (including SD/non-CR/non-PD), DoR (first response until progression/death), and PFS (randomization to progression/death), with imaging conducted at protocol-specified intervals.

Eligible patients (≥18 years) must have non-progressed limited-stage SCLC after chemoradiotherapy, ECOG 0-1, and >12-week life expectancy. Key exclusions include: mixed histology/extensive-stage disease, progression during CRT, prior B7-H3 therapy, major surgery within 4 weeks, active ILD/pneumonitis, uncontrolled comorbidities (cardiovascular/diabetic/hypertensive disorders), recent thrombosis/serious bleeding/infections, or conditions compromising safety per investigator assessment. Fertility requirements and pregnancy restrictions apply.

The primary endpoints assess the efficacy of HS-20093 versus active surveillance, with progression-free survival (PFS) measured from randomization to disease progression or death (whichever occurs first) by Independent Review Committee (IRC) per RECIST v1.1 over approximately 6 years. Overall survival (OS), the second primary endpoint, is defined as time from randomization to death from any cause during the same 6-year period.

Secondary efficacy assessments include PFS at 12/18 months (PFS12/PFS18), objective response rate (ORR, CR+PR), disease control rate (DCR, CR+PR+SD), and duration of response (DoR) - all evaluated by both IRC and investigators per RECIST v1.1 through 6 years. Additional measures include 24/36-month survival rates (OS24/OS36) and treatment-emergent adverse events (graded by NCI CTCAE v5.0) monitored until 90 days post-treatment.

Eligible patients (≥18 years) must have advanced solid tumors, ≥1 measurable lesion (RECIST 1.1), ECOG 0-1, and ≥12-week life expectancy. Key exclusions include prior PARPi/B7-H4/B7-H3 therapy, uncontrolled comorbidities (cardiovascular, diabetic, hypertensive), active infections (HBV/HCV/HIV), Grade ≥2 toxicities, pleural/abdominal effusion requiring intervention, brain metastasis, or conditions affecting safety/compliance. Fertile participants must use contraception; pregnancy/breastfeeding is prohibited. Live vaccines within 4 weeks or active autoimmune diseases are exclusionary.

The study aims to determine the maximum tolerated dose (MTD) and maximum applicable dose (MAD) of HS-10502 during dose escalation (Stage 1), with MTD defined as the dose where ≥2/2-6 subjects experience dose-limiting toxicities (DLTs) in Cycle 1 (21 days). MAD considers PK exposure plateau, safety risks, and optimal PK-PD target concentration. In Stage 2 (dose expansion), primary efficacy is measured by objective response rate (ORR), assessing confirmed CR/PR per RECIST v1.1 (solid tumors) or RECIST v1.1+PCWG3 (prostate cancer) over ~2 years.

Safety is evaluated via treatment-emergent adverse events (NCI CTCAE v5.0) from Cycle 1 Day 1 to 28 days post-treatment. PK parameters include Cmax, Tmax, AUC0-t (Cycle 1), and steady-state metrics (Css,max, Tss,max, Css,min, AUCss; Cycle 2). Secondary efficacy endpoints span ORR, disease control rate (DCR: CR+PR+SD≥5 weeks), duration of response (DoR), PFS (all solid tumors except prostate), rPFS (prostate, RECIST v1.1+PCWG3), OS (~4 years), and tumor-specific measures: CA-125 reduction ≥50% (ovarian) and PSA50 response/time to PSA progression (prostate

Eligible subjects (≥18 years) must have histologically confirmed advanced solid tumors, ≥1 measurable lesion (RECIST 1.1), ECOG 0-1, and ≥12-week life expectancy. Key exclusions: prior B7-H3 therapy, recent chemotherapy/radiotherapy (within 2-4 weeks), untreated metastases/effusions, major surgery within 4 weeks, Grade >2 toxicities, uncontrolled comorbidities (cardiovascular/diabetes/hypertension), active infections (HBV/HCV/HIV), or CYP3A4/CYP2D6-modifying drugs. Fertile participants require contraception; pregnancy/breastfeeding is prohibited. Conditions compromising safety or compliance per investigator judgment are exclusionary.

Safety analysis includes AE incidence/severity (NCI CTCAE v5.0) from first dose to 90 days post-treatment. PK parameters (Cmax, Tmax, T1/2, AUC0-t) are evaluated during Cycle 1 (21-day cycles). Immunogenicity assesses anti-drug antibodies (ADAs) up to 90 days post-treatment. Secondary efficacy measures include IRC-confirmed ORR, duration of response (DoR), disease control rate (DCR: CR+PR+SD≥5 weeks), progression-free survival (PFS), radiographic PFS (rPFS for mCRPC), and overall survival (OS) over 24 months. Prostate cancer cohorts add PSA-specific endpoints: response rate (≥50% decline) and time to PSA progression.

Eligible patients (≥18 years) must have confirmed metastatic sarcoma (Cohort 1: soft tissue; Cohort 2: osteosarcoma) with ≥1 measurable lesion (RECIST 1.1), ECOG 0-1, and ≥12-week life expectancy. Key exclusions include prior B7-H3/TOP1i treatment (cohort-specific), recent anticancer therapies (chemotherapy/radiotherapy/antibodies within 2-4 weeks), major surgery within 4 weeks, uncontrolled comorbidities, active infections, or pregnancy. Fertile participants must use contraception throughout the study.

Key efficacy outcomes include investigator-assessed objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS) over 24 months. Pharmacokinetic parameters (Cmax, Tmax, T1/2, AUC0-t) and anti-drug antibody (ADA) levels will be monitored from first dose through study completion. Confirmed tumor responses require ≥1 repeat imaging (≥4 weeks for CR/PR, ≥5 weeks for SD).

Eligible patients (≥18 years) must have histologically confirmed advanced/metastatic solid tumors (including esophageal carcinoma) with ≥1 measurable lesion (RECIST 1.1), ECOG 0-1, and >12-week life expectancy. Key exclusions: prior B7-H3 therapy; recent anticancer treatments (chemotherapy/radiation/MAbs within 2-4 weeks); major surgery within 4 weeks; significant esophageal tumor invasion (aorta/trachea); active infections (e.g., hepatitis B/C); pregnancy; or HS-20093 hypersensitivity. Contraception is mandatory.

Secondary endpoints include duration of response (DOR), disease control rate (DCR; CR/PR/SD requiring ≥5-week assessment), progression-free survival (PFS), and overall survival (OS). Safety evaluates AE incidence/severity (CTCAE v5.0) from first dose to 90 days post-treatment, while pharmacokinetics and anti-drug antibody (ADA) incidence are monitored from Cycle 1 Day 1 through 90 days post-treatment.

Eligible patients (≥18 years) must have confirmed advanced/metastatic solid tumors, ECOG 0-1, ≥1 measurable lesion (RECIST 1.1), and ≥12-week life expectancy. Dose escalation includes treatment-refractory cases; dose expansion prioritizes treatment-naïve patients. Exclusions: prior B7-H3 therapy; intolerance to PD-L1 inhibitors/cisplatin/enzalutamide/cetuximab; recent anticancer treatments (chemotherapy/radiation/MAbs/surgery within 2-4 weeks); uncontrolled comorbidities; active infections; or pregnancy. Contraception is mandatory.

Key endpoints include safety (AE incidence/severity per CTCAE v5.0 through 90 days post-treatment) and efficacy measures: ORR, DCR, DOR, PFS, and OS per RECIST 1.1 (PCWG3 for prostate cancer). Prostate-specific endpoints include rPFS, TTPP, PSA response rate (≥50% decline), and TFST. Pharmacokinetics (Cmax, Tmax, T1/2, AUC0-t) and ADA incidence are monitored from first dose to study completion (24 months).

Eligible participants (18-75 years) must have advanced/metastatic malignancies refractory to standard therapy, measurable lesions (RECIST 1.1), ECOG 0-1, adequate organ function, and use contraception. Exclusions involve active CNS metastases, macrovascular invasion, symptomatic effusions, secondary malignancies, immunodeficiency, uncontrolled cardiac/ILD conditions, hepatitis B/C, recent anticoagulation/anti-tumor therapy, unresolved prior toxicities, or hypersensitivity to SHR-A1921 components.

Eligible participants (18-75 years) must have advanced/metastatic malignancies refractory to standard therapy, measurable lesions (RECIST 1.1), ECOG 0-1, adequate organ function, and use contraception. Exclusions involve active CNS metastases, macrovascular invasion, symptomatic effusions, secondary malignancies, immunodeficiency, uncontrolled cardiac/ILD conditions, hepatitis B/C, recent anticoagulation/anti-tumor therapy, unresolved prior toxicities, or hypersensitivity to SHR-A1921 components.

Eligible participants (18-75 years) must have advanced/metastatic malignancies refractory to standard therapy, measurable lesions (RECIST 1.1), ECOG 0-1, adequate organ function, and use contraception. Exclusions involve active CNS metastases, macrovascular invasion, symptomatic effusions, secondary malignancies, immunodeficiency, uncontrolled cardiac/ILD conditions, hepatitis B/C, recent anticoagulation/anti-tumor therapy, unresolved prior toxicities, or hypersensitivity to SHR-A1921 components.

Eligible patients are HER2-negative advanced breast cancer patients (18-75 years, ECOG 0-1) with 1-2 prior systemic therapies, measurable lesions (RECIST v1.1), stable brain metastases allowed, and adequate organ function. Exclusions: active brain metastases needing treatment, prior PD- (L)1/HER2/TROP-2 therapy, uncontrolled infections, significant comorbidities (autoimmune, cardiac, pulmonary), recent live vaccines, or pregnancy.

Eligible patients are HR+/HER2-, PD-L1+ advanced/metastatic breast cancer patients (18-75 years, ECOG 0-1) with ≥2 prior endocrine therapies (including CDK4/6i) and ≥1 chemotherapy line, measurable lesions (RECIST v1.1), and life expectancy ≥3 months. Exclusions: untreated/symptomatic CNS metastases (except stable post-treatment cases), prior TROP-2/PD- (L)1/ADC therapy, uncontrolled effusions, active infections, autoimmune/cardiovascular/lung diseases, recent immunosuppressants/live vaccines, or other malignancies within 5 years.

Eligible patients are ≥18 years with locally advanced/metastatic breast cancer (any HR status, prior ADC and CDK4/6i if HR+), measurable disease (RECIST 1.1), adequate organ function (hematologic/hepatic/cardiac), ECOG≤2, and life expectancy≥3 months. Exclusions: untreated CNS metastases, uncontrolled effusions/heart disease/HIV/hepatitis B/C, recent immunosuppressants/surgery/radiotherapy, active autoimmune conditions, pregnancy, other malignancies within 5 years, or severe comorbidities per investigator judgment.

Eligible patients are ≥18 years with HR-/HER2- metastatic breast cancer, ECOG 0-2, MRI-confirmed untreated brain metastases (≥1 cm), stable neurologic symptoms, and adequate organ function (hematologic/hepatic/cardiac). Exclusions: leptomeningeal/cystic metastases, uncontrolled effusions, recent anti-cancer therapies (including bevacizumab/TROP-2 ADC), active HBV/HCV/HIV, severe cardiac/neurologic conditions, pregnancy, or other malignancies within 5 years (except cured non-invasive cancers). Investigators may exclude patients with uncontrolled comorbidities.

Exclusion criteria include recent radiotherapy/chemotherapy/immunotherapy (except bisphosphonates for bone mets), uncontrolled CNS metastases, significant cardiac disease (e.g., recent MI/CHF), unresolved grade≥1 treatment-related AEs (excluding alopecia), major surgery within 3 weeks, pregnancy/lactation, or other malignancies (except cured non-melanoma skin/CIS cervical cancer) within 5 years.

This study evaluates the overall response rate (ORR), defined as the proportion of participants achieving complete or partial remission (per RECIST 1.1) from randomization to disease progression/death, alongside secondary endpoints including clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), CTCAE v5.0-assessed adverse events, and exploratory biomarker analysis in tumor, paracancerous tissues, blood, and fecal samples.

Eligible participants must be female (≥18 years) with HR+/HER2- locally advanced or recurrent metastatic breast cancer, having previously received CDK4/6 inhibitors. They must have ≥1 measurable lesion (RECIST 1.1), adequate organ function (HB≥90g/L, ANC≥1.5x10^9/L, PLT≥75x10^9/L, ALT/AST≤3xULN [≤5xULN if liver mets], Cr clearance >50mL/min), ECOG≤2, and life expectancy≥3 months. Fertile women must use contraception during and 3 months post-study.

Exclusions include other active malignancies (except cured localized cancers), recent antitumor therapy (within 28 days; waived if drug half-life ≥5×), uncontrolled cardiac conditions (NYHA≥II, LVEF<50%, QTc>450/470ms), hypertension unmanageable by medication, malabsorption risks (arm 2 only), bleeding risks (active ulcers, INR>1.5×ULN), or uncontrolled coagulopathy (aPTT>1.5×ULN).

This study assesses the objective response rate (ORR) based on RECIST 1.0 criteria and disease control rate (DCR) including complete/partial responses and stable disease, evaluated every 2 cycles (21-day cycles for arms 1,3,4; 28-day for arm 2). Secondary endpoints include median progression-free survival (PFS) and overall survival (OS) tracked over 2 years, plus adverse events (CTCAE 5.0) monitored from consent until 30 days post-treatment.

Eligible participants (18-75 years) must have histologically confirmed locally advanced/metastatic salivary gland carcinoma, stratified by HER-2/AR status (arms 1-4), ≥1 measurable lesion (RECIST 1.1), ECOG 0-1, and adequate organ function (HB≥90g/L, ANC≥1.5×10⁹/L, PLT≥80×10⁹/L, ALT/AST≤2.5×ULN [≤5×ULN if liver mets], Cr≤1×ULN). Fertile individuals must use contraception during and 8 weeks post-study.

Eligible participants (18-75 years) must have histologically/cytologically confirmed unresectable locally advanced or metastatic non-small cell lung cancer, ≥1 measurable lesion (RECIST v1.1), ECOG 0-1, and adequate organ function. Key exclusions include untreated CNS/metastasis, uncontrolled symptomatic effusions, active autoimmune/cardiac disease, prior topoisomerase I inhibitors/TROP-2 ADC/anti-PD-1/L1/CTLA-4 therapy, or hypersensitivity to SHR-A1921/Adebrelimab components.

Eligible participants (18-75 years) must have metastatic NSCLC (AJCC/UICC 8th ed.) progressing after standard/antibody-conjugated therapy, ≥1 measurable lesion (RECIST 1.1), ECOG 0-1, life expectancy ≥12 weeks, and adequate organ function, with contraception use mandated. Exclusions include untreated CNS metastases, active effusions, prior thoracic radiotherapy/surgery, secondary malignancies, uncontrolled comorbidities (cardiac/pulmonary/HTN), hepatitis B/C, unresolved treatment toxicity, or hypersensitivity to study drugs (SHR-A1921/A2009), with investigator discretion for other risk factors.

Exclusions include prior topoisomerase I inhibitors/TROP2 therapy, grade≥3 immune-related AEs, untreated/symptomatic CNS metastases, uncontrolled effusions, recent radiotherapy/chemo/surgery (within 4-6 weeks), other malignancies (5 years), interstitial lung disease, active infections (TB/HBV/HCV), uncontrolled hypertension (≥140/90 mmHg), severe allergies to study drugs, or investigator-judged risks (e.g., substance abuse, psychosocial factors).

Objective response rate (ORR), defined as the proportion of patients with tumor shrinkage/disappearance per RECIST v1.1, will be assessed from screening through study completion (average 2 years), alongside progression-free survival (PFS), duration of response (DoR), overall survival (OS), and disease control rate (DCR) for comprehensive efficacy evaluation over the same timeframe.

Eligibility requires histologically/cytologically confirmed advanced/metastatic NSCLC (IASLC TNM stage IIIb-IV) unsuitable for curative treatment, progression post-immunotherapy/platinum chemo, ≥1 measurable lesion (RECIST v1.1), ECOG 0-1, life expectancy ≥12 weeks, and adequate organ function (ANC≥1.5×10⁹/L, ALT/AST≤3×ULN, LVEF≥50%). Non-squamous patients must lack EGFR/ALK/ROS1 mutations. Contraception is mandatory (6 months post-treatment).

The primary efficacy measure is Objective Response Rate (ORR) assessed by investigators per RECIST v1.1 from screening through study completion (average 1 year), accompanied by additional evaluations including Duration of Response (DoR), Disease Control Rate (DCR), and Progression-Free Survival (PFS) using RECIST v1.1, while Overall Survival (OS) and CA-125 Response per GCIG criteria are also analyzed over the same timeframe.

Exclusions involve uncontrolled symptomatic effusions, prior/concurrent malignancies, active hepatitis B/C, interstitial lung disease (ILD), uncontrolled cardiac conditions, recent thrombosis/bleeding (≥CTCAE grade 2), gastrointestinal perforation/fistula, intestinal obstruction, severe pre-dose infections, prior TOP1 inhibitor/ADC therapy, unresolved toxicity (≥grade 2), hypersensitivity to SHR-A1921 components, or other investigator-determined contraindications.

The primary endpoint is Progression-Free Survival (PFS) evaluated by a Blinded Independent Review Committee (BIRC) according to RECIST 1.1 over a 1-year period, supplemented by secondary endpoints including Overall Survival (OS), Objective Response Rate (ORR), Duration of Response (DoR), Disease Control Rate (DCR) assessed by site investigators per RECIST 1.1, alongside Response Rate (RR) by RECIST 1.1/GCIG criteria and CA-125 Response per GCIG criteria, with Adverse Events also monitored throughout the study.

Eligible participants must be female, aged ≥18, with pathologically confirmed platinum-resistant epithelial ovarian, primary peritoneal, or fallopian tube cancer, provide fresh/archived tumor tissue, have ≥1 measurable lesion (RECIST 1.1), ECOG 0-1, life expectancy ≥12 weeks, adequate organ function, and agree to contraception. Voluntary informed consent is mandatory.

Eligible participants must provide informed consent, supply adequate tumor tissue samples, and have confirmed advanced solid tumors (recurrent, unresectable, or metastatic) after failing standard therapy, with ECOG 0-1. Exclusion criteria include uncontrolled symptomatic effusions, untreated brain/meningeal metastases, prior malignancies, AIDS, uncontrolled cardiovascular disease (NYHA ≥2), interstitial lung disease, recent hemorrhage (≥grade 2), active hepatitis B, SHR-1921 hypersensitivity, or other investigator-determined interference factors.

Pharmacokinetic parameters of SHR-1921 will be evaluated, including maximum plasma concentration (Cmax), area under the curve (AUC 0-∞), time to reach Cmax (Tmax), drug clearance (CL/F), and terminal elimination half-life (t1/2). Additionally, immunogenicity will be assessed by measuring anti-drug antibodies (ADA) in participant blood samples throughout the study period.

Eligible participants (18-75 years, ECOG 0-1) must have measurable lesions (RECIST v1.1); Phase 1b: advanced solid tumors; Phase II: metastatic NSCLC. Exclusions include untreated brain/meningeal metastases, uncontrolled symptomatic effusions, concurrent malignancies (except certain cured cancers), uncontrolled hypertension, active autoimmune diseases, or tuberculosis. Contraception is required for WOCBP and male partners.

Eligible patients (18-75 years, ECOG 0-1, life expectancy ≥12 weeks) must have histologically confirmed advanced/metastatic solid tumors, ≥1 measurable lesion (RECIST v1.1), and adequate organ function. Exclusions include active CNS metastases, uncontrolled effusions/pain, recent anti-tumor therapy (≤4 weeks), interstitial lung disease, severe cardiovascular conditions, HIV/HBV/HCV positivity, drug allergies, or pregnancy/lactation.

Eligible participants (18-75 years, ECOG 0-1, expected survival ≥12 weeks) must provide consent and have ≥1 measurable lesion (RECIST v1.1). Exclusions include: uncontrolled psychiatric/medical conditions; HRS-4642 hypersensitivity; recent surgery/trauma (≤28/7 days); live vaccine use (≤28 days); HIV/immunodeficiency; active/past untreated tuberculosis; hepatitis B; pancreatitis; uncontrolled cardiovascular/thrombotic events; or gastrointestinal obstruction (≤6 months).

Eligible patients (≥18 yrs) have confirmed relapsed/refractory B-cell lymphoma, ≥1 measurable lesion (nodal >1.5 cm/extranodal >1.0 cm), ECOG 0-1, and life expectancy >12 weeks. Exclusions: recent stem cell/CAR-T therapy (≤12 weeks), major surgery (≤4 weeks), anti-tumor treatment (≤2 weeks), CNS involvement, active HBV/HCV/HIV, uncontrolled infections, or severe cardiovascular disease.

Eligible patients (≥18 yrs) have confirmed relapsed/refractory B-cell lymphoma, ≥1 measurable lesion (nodal >1.5 cm/extranodal >1.0 cm), ECOG 0-1, and life expectancy >12 weeks. Exclusions: recent stem cell/CAR-T therapy (≤12 weeks), major surgery (≤4 weeks), anti-tumor treatment (≤2 weeks), CNS involvement, active HBV/HCV/HIV, uncontrolled infections, or severe cardiovascular disease.

Eligible patients (≥18 yrs) have confirmed relapsed/refractory B-cell lymphoma, ≥1 measurable lesion (nodal >1.5 cm/extranodal >1.0 cm), ECOG 0-1, and life expectancy >12 weeks. Exclusions: recent stem cell/CAR-T therapy (≤12 weeks), major surgery (≤4 weeks), anti-tumor treatment (≤2 weeks), CNS involvement, active HBV/HCV/HIV, uncontrolled infections, or severe cardiovascular disease.

Eligible patients (≥18 yrs) have confirmed relapsed/refractory B-cell lymphoma, ≥1 measurable lesion (nodal >1.5 cm/extranodal >1.0 cm), ECOG 0-1, and life expectancy >12 weeks. Exclusions: recent stem cell/CAR-T therapy (≤12 weeks), major surgery (≤4 weeks), anti-tumor treatment (≤2 weeks), CNS involvement, active HBV/HCV/HIV, uncontrolled infections, or severe cardiovascular disease.

Eligible patients (≥18 yrs) have confirmed relapsed/refractory B-cell lymphoma, ≥1 measurable lesion (nodal >1.5 cm/extranodal >1.0 cm), ECOG 0-1, and life expectancy >12 weeks. Exclusions: recent stem cell/CAR-T therapy (≤12 weeks), major surgery (≤4 weeks), anti-tumor treatment (≤2 weeks), CNS involvement, active HBV/HCV/HIV, uncontrolled infections, or severe cardiovascular disease.

Eligible patients (≥18 yrs) have confirmed relapsed/refractory B-cell lymphoma, ≥1 measurable lesion (nodal >1.5 cm/extranodal >1.0 cm), ECOG 0-1, and life expectancy >12 weeks. Exclusions: recent stem cell/CAR-T therapy (≤12 weeks), major surgery (≤4 weeks), anti-tumor treatment (≤2 weeks), CNS involvement, active HBV/HCV/HIV, uncontrolled infections, or severe cardiovascular disease.

Eligible patients (≥18 yrs) include relapsed/refractory or treatment-naive B-cell NHL cases (≥1 measurable lesion: nodal >1.5cm/extranodal >1.0cm), ECOG 0-1, life expectancy >3 months. Exclusions: recent stem cell/CAR-T therapy (≤12 weeks), major surgery (≤4 weeks), active HBV/HCV/HIV, uncontrolled infections, or severe cardiovascular/CNS involvement.

Eligible subjects were 18-75 years with advanced solid tumors (measurable per RECIST 1.1), ECOG 0-1, life expectancy ≥3 months, and adequate organ function. Key exclusions: CNS metastasis, recent malignancies (5 years), uncontrolled pain/effusions, severe CVD/interstitial lung disease, active HBV/HCV/HIV, unresolved prior toxicities (CTCAE >Grade 1), recent anticancer therapy/surgery (4 weeks), pregnancy, or drug allergies. Additional exclusions per investigator discretion.

Eligible NSCLC patients aged 18-75 with ECOG 0-1, measurable lesions (RECIST v1.1), and adequate organ function must provide tumor tissue. Excluded are those with CNS metastasis, recent major surgery, unresolved toxicities (>CTCAE v5.0 Grade 2), active HBV/HCV, uncontrolled cardiovascular disease, or prior malignancies within 5 years. Pregnancy and inadequate contraception are also exclusionary.

Eligible patients (18-75 years, ECOG 0-1) must have histologically confirmed advanced/metastatic solid tumors (measurable per RECIST v1.1) and adequate organ function. Key exclusions: active CNS metastases, prior ADC therapy, unresolved AEs (>CTCAE v5.0 Grade 1), uncontrolled infections/cardiovascular diseases, recent major surgery/radiotherapy, or conditions compromising study safety per investigator judgment. Contraception is mandatory.