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 &ge;5&times;), uncontrolled cardiac conditions (NYHA&ge;II, LVEF<50%, QTc>450/470ms), hypertension unmanageable by medication, malabsorption risks (arm 2 only), bleeding risks (active ulcers, INR>1.5&times;ULN), or uncontrolled coagulopathy (aPTT>1.5&times;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, &ge;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, &ge;1 measurable lesion (RECIST 1.1), ECOG 0-1, life expectancy &ge;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&ge;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 (&ge;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 (&ge;CTCAE grade 2), gastrointestinal perforation/fistula, intestinal obstruction, severe pre-dose infections, prior TOP1 inhibitor/ADC therapy, unresolved toxicity (&ge;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 &ge;2), interstitial lung disease, recent hemorrhage (&ge;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 &ge;12 weeks) must have histologically confirmed advanced/metastatic solid tumors, &ge;1 measurable lesion (RECIST v1.1), and adequate organ function. Exclusions include active CNS metastases, uncontrolled effusions/pain, recent anti-tumor therapy (&le;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 &ge;12 weeks) must provide consent and have &ge;1 measurable lesion (RECIST v1.1). Exclusions include: uncontrolled psychiatric/medical conditions; HRS-4642 hypersensitivity; recent surgery/trauma (&le;28/7 days); live vaccine use (&le;28 days); HIV/immunodeficiency; active/past untreated tuberculosis; hepatitis B; pancreatitis; uncontrolled cardiovascular/thrombotic events; or gastrointestinal obstruction (&le;6 months).