Eligible patients (18-75 years) must have HER2-positive (IHC 3+/2+) metastatic urothelial cancer with ≥1 measurable lesion (RECIST v1.1), ECOG 0-1, and adequate organ function, following ≥1 prior chemotherapy failure. Key exclusions include active infections, CNS metastasis, uncontrolled systemic/autoimmune diseases, recent immunotherapy (≤4 weeks), pregnancy, or investigator-deemed ineligibility. LVEF must be ≥50%, with prior treatment toxicities resolved to ≤Grade 1.

Secondary endpoints include investigator-assessed ORR, Duration of Response (DoR), Time to Response (TTR), Disease Control Rate (DCR), Progression-Free Survival (PFS), and Overall Survival (OS), all evaluated over 12 months. Safety assessments involve adverse event monitoring (30 days post-treatment), pharmacokinetic concentration-time analysis, and anti-drug antibody (ADA) incidence among all treated patients.

Inclusion: HER2-low metastatic breast cancer (≥1 prior systemic therapy), ECOG 0-1, measurable disease (RECIST 1.1), LVEF≥50%, adequate organ function. Exclusion: Active CNS metastases, uncontrolled infections (HBV/HCV/HIV), severe cardiac/autoimmune diseases, recent thromboembolism (≤3 months), pregnancy/lactation, or prior grade≥3 hypersensitivity to trastuzumab components.

Eligible patients (18-75 years) must have HER2-positive (IHC 3+/2+) metastatic urothelial cancer with ≥1 measurable lesion (RECIST v1.1), ECOG 0-1, and adequate organ function, following ≥1 prior chemotherapy failure. Key exclusions include active infections, CNS metastasis, uncontrolled systemic/autoimmune diseases, recent immunotherapy (≤4 weeks), pregnancy, or investigator-deemed ineligibility. LVEF must be ≥50%, with prior treatment toxicities resolved to ≤Grade 1.

Secondary endpoints include investigator-assessed ORR, Duration of Response (DoR), Time to Response (TTR), Disease Control Rate (DCR), Progression-Free Survival (PFS), and Overall Survival (OS), all evaluated over 12 months. Safety assessments involve adverse event monitoring (30 days post-treatment), pharmacokinetic concentration-time analysis, and anti-drug antibody (ADA) incidence among all treated patients.

Inclusion: HER2-low metastatic breast cancer (≥1 prior systemic therapy), ECOG 0-1, measurable disease (RECIST 1.1), LVEF≥50%, adequate organ function. Exclusion: Active CNS metastases, uncontrolled infections (HBV/HCV/HIV), severe cardiac/autoimmune diseases, recent thromboembolism (≤3 months), pregnancy/lactation, or prior grade≥3 hypersensitivity to trastuzumab components.

Eligible patients (18-75 years) must have HER2-positive (IHC 3+/2+) metastatic urothelial cancer with ≥1 measurable lesion (RECIST v1.1), ECOG 0-1, and adequate organ function, following ≥1 prior chemotherapy failure. Key exclusions include active infections, CNS metastasis, uncontrolled systemic/autoimmune diseases, recent immunotherapy (≤4 weeks), pregnancy, or investigator-deemed ineligibility. LVEF must be ≥50%, with prior treatment toxicities resolved to ≤Grade 1.

Secondary endpoints include investigator-assessed ORR, Duration of Response (DoR), Time to Response (TTR), Disease Control Rate (DCR), Progression-Free Survival (PFS), and Overall Survival (OS), all evaluated over 12 months. Safety assessments involve adverse event monitoring (30 days post-treatment), pharmacokinetic concentration-time analysis, and anti-drug antibody (ADA) incidence among all treated patients.

Eligible patients (18-75 years) must have HER2-positive (IHC 3+/2+) metastatic urothelial cancer with ≥1 measurable lesion (RECIST v1.1), ECOG 0-1, and adequate organ function, following ≥1 prior chemotherapy failure. Key exclusions include active infections, CNS metastasis, uncontrolled systemic/autoimmune diseases, recent immunotherapy (≤4 weeks), pregnancy, or investigator-deemed ineligibility. LVEF must be ≥50%, with prior treatment toxicities resolved to ≤Grade 1.

Secondary endpoints include investigator-assessed ORR, Duration of Response (DoR), Time to Response (TTR), Disease Control Rate (DCR), Progression-Free Survival (PFS), and Overall Survival (OS), all evaluated over 12 months. Safety assessments involve adverse event monitoring (30 days post-treatment), pharmacokinetic concentration-time analysis, and anti-drug antibody (ADA) incidence among all treated patients.

Inclusion: HER2-positive breast cancer (unresectable/metastatic), prior anti-HER2 therapy failure (Phase II: trastuzumab/TKI/ADC-resistant; Phase III: 1-2 prior lines excluding ADCs), measurable disease (RECIST 1.1), ECOG 0-1, adequate organ function. Exclusion: Active CNS metastases, uncontrolled infections (HBV/HCV/HIV), severe cardiac/pulmonary diseases, prior hypersensitivity to trastuzumab components, recent major surgery/radiotherapy (<4 weeks), Child-Pugh B/C cirrhosis, or >Grade 1 neuropathy. Contraception required for reproductive-age participants.

Progression-Free Survival (PFS) as assessed by Independent Review Committee (IRC) is the primary efficacy endpoint, defined as time from treatment initiation to disease progression or death (per RECIST v1.1) over 36 months. Secondary objectives include pharmacokinetic analysis (drug concentration-time curve) and immunogenicity assessment (anti-drug antibody incidence).

Inclusion criteria: HER2-positive breast cancer patients (18-75 years) with liver metastasis (confirmed by central lab), measurable lesions (RECIST v1.1), ECOG 0-1, life expectancy &ge;12 weeks, and adequate organ function. Exclusion criteria: Prior ADC treatment, CNS metastasis, severe neuropathy (&ge;Grade 2), uncontrolled infections/systemic diseases (e.g., cardiac, hepatic cirrhosis with single metastasis &ge;10 cm), active autoimmune disease requiring immunosuppressants, or prior hypersensitivity to trastuzumab components. Effective contraception is mandatory for participants of childbearing potential.

Secondary efficacy endpoints include investigator-assessed ORR, Duration of Response (DoR), Clinical Benefit Rate (CBR=CR+PR+SD≥6 months), Time to Response (TTR), Disease Control Rate (DCR=CR+PR+SD), Progression-Free Survival (PFS), and Overall Survival (OS). Safety assessments (AEs) and pharmacokinetics (drug concentration-time curve) are monitored during treatment and post-treatment follow-up, with immunogenicity analyzed via anti-drug antibody (ADA) incidence.

Inclusion criteria: HER2-positive (IHC 2+/3+) carcinoma of unknown primary origin (squamous/adenocarcinoma) patients (&ge;18 years) with &ge;1 prior systemic therapy line, measurable disease (RECIST 1.1), ECOG 0-1, LVEF&ge;50%, and adequate organ function. Exclusion criteria: Active/uncontrolled metastases (CNS/third-space effusions), severe cardiac/infectious diseases (HBV/HCV/HIV), autoimmune disorders requiring immunosuppressants, allergy to MRG002 components, pregnancy/lactation, or other investigator-assessed ineligibility. Contraception is mandatory during and 6 months post-treatment.

Inclusion criteria: HER2-positive (IHC 3+ or 2+) biliary tract cancer patients (18-75 years) with unresectable/metastatic disease, &ge;1 prior therapy failure, measurable lesions (RECIST v1.1), ECOG 0-1, LVEF&ge;50%, and adequate organ function. Exclusion criteria: Severe allergies to MRG002 components, active infections (HBV/HCV/HIV), CNS metastasis, uncontrolled effusions requiring drainage, autoimmune diseases, decompensated cirrhosis, or pregnancy/lactation. Contraception is mandatory during and 6 months post-treatment.

Secondary endpoints include investigator-assessed ORR, duration of response (DOR), time to response (TTR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Safety is monitored via adverse events (AEs) up to 30 days post-treatment. Pharmacokinetic (PK) parameters, including concentration-time curve, and immunogenicity (anti-drug antibody, ADA) incidence are analyzed.

Inclusion criteria: HER2-positive (IHC 3+ or IHC 2+/ISH+) or low HER2 (IHC 1+ or IHC 2+/ISH-) gastric/GEJ cancer patients (&ge;18 years) with progression after platinum/fluoropyrimidine &plusmn; anti-HER2 therapy, measurable disease (RECIST v1.1), ECOG 0-1, and adequate organ function. Exclusion criteria: Prior HER2-ADC exposure, untreated CNS metastases, severe cardiac/pulmonary disease, active infections (HBV/HCV/HIV/syphilis), recent major surgery, or uncontrolled comorbidities. Contraception is required during and 180 days post-treatment.

Inclusion criteria: HER2-positive metastatic/unresectable cancer patients (&ge;18 years) with prior standard therapy failure, measurable disease (RECIST v1.1), ECOG 0-1, adequate organ function, and available tumor tissue. Exclusion criteria: Unresolved Grade >1 toxicities from prior treatments, untreated CNS metastases, recent major surgery, severe cardiac/pulmonary conditions, active infections (HBV/HCV/HIV), uncontrolled comorbidities, or hypersensitivity to MRG002 components. Pregnancy and strong CYP3A4 inhibitor use are prohibited.

The primary objectives include determining the Maximum Tolerated Dose (MTD) by assessing dose-limiting toxicities (DLT) during the first 21-day cycle and establishing the Recommended Phase II Dose (RP2D) for MRG002. Key efficacy measures include Objective Response Rate (ORR) assessed by Independent Central Review (ICR) per RECIST v1.1 over 24 months, alongside comprehensive safety evaluations of adverse events (AEs) coded via MedDRA until 45 days post-treatment.

Secondary efficacy endpoints (Duration of Response [DoR], Disease Control Rate [DCR], Progression-Free Survival [PFS]) will undergo sensitivity analyses based on investigator assessments. Pharmacokinetic (PK) parameters (Cmax, AUClast) for MRG002, total antibody (TAb), and Monomethyl Auristatin E (MMAE) will be derived from serial blood samples, with immunogenicity monitored via anti-drug antibody (ADA) incidence throughout the study.

The study excludes patients with small-cell/mixed lung cancer, uncontrolled comorbidities (hypertension, bleeding disorders), autoimmune/active infections, or live vaccinations within 30 days. Other disqualifiers include interstitial lung disease, pleural effusions requiring frequent drainage, or conditions compromising safety/study integrity per investigator judgment. Strict contraception (120 days post-treatment) and avoidance of immunotherapies/systemic steroids are mandated.

ORR assessed by Independent Review Committee (IRC) is the primary efficacy endpoint, defined as the proportion of subjects achieving CR or PR per RECIST v1.1 over 12 months. Secondary assessments include investigator-evaluated ORR, DCR (CR+PR+SD), DOR, PFS, and OS, all measured over 12 months. Safety monitoring tracks AEs until 45 days post-treatment, while PK analysis evaluates drug concentration-time curves and immunogenicity (ADA incidence) up to 30 days post-treatment.

NSCLC patients with HER2 mutations (aged 18-75, life expectancy ≥3 months) who failed prior SOC therapy are eligible if they have measurable disease (RECIST v1.1), ECOG 0-1, and adequate organ function. Key exclusions: prior HER2-ADC/antibody treatment, active CNS metastases, uncontrolled infections (HBV/HCV/HIV), severe cardiac/pulmonary conditions, recent major surgery/immunotherapy, or concurrent strong CYP3A4 modifiers. Pregnancy and inadequate contraception are prohibited.

Eligibility requires HER2-positive solid tumor patients (18-75 years, ECOG 0-1) with progressed/refractory disease, &ge;1 measurable lesion (RECIST 1.1), and adequate organ function. Exclusions: recent antitumor therapy (&le;3 weeks), uncontrolled comorbidities (cardiac/pulmonary/GI), active infections (HBV/HCV/HIV), major surgery (&le;4 months), or corticosteroid use (&le;4 weeks). Pregnancy, inadequate contraception, or investigator-deemed ineligibility also preclude participation.

The study aims to determine the Maximum Tolerated Dose (MTD) of MRG002, defined as the highest dose where ≤1/6 patients experience dose-limiting toxicities (DLT) during the first 28-day cycle. The Recommended Phase II Dose (RP2D) will be established based on comprehensive safety, efficacy, and PK assessments over 6 months. Adverse events (AEs) will be monitored from baseline through 49 days post-treatment, capturing all treatment-related reactions.

Eligible patients (18-75 years) must have HER2-positive advanced solid tumors with measurable lesions (RECIST v1.1), ECOG 0-1, and adequate organ function. Key exclusions include prior ADC/immunotherapy (&le;60 days), steroid use (&le;14 days), active infections, CNS metastases, significant cardiorespiratory disease, or pregnancy. Anthracycline exposure is capped at &le;450 mg/m2 doxorubicin equivalent. Investigators may exclude patients deemed unsuitable for study participation.

The study will evaluate dose-limiting toxicities (DLTs) occurring within 28 days post-first dose to establish the safety profile of MRG002. Adverse events will be monitored from consent until 90 days after treatment completion, with all potential drug-related reactions recorded. The Recommended Phase II Dose (RP2D) will be determined based on 24-month safety, efficacy, and pharmacokinetic data.

Efficacy outcomes include Objective Response Rate (ORR), Duration of Response (DOR), Disease Control Rate (DCR), Progression-Free Survival (PFS), Time to Response (TTR), and Overall Survival (OS), all measured over 24 months. Pharmacokinetic profiling will examine concentration-time curves, while immunogenicity will assess anti-drug antibody (ADA) incidence - both monitored up to 90 days post-treatment.

Eligible patients (18-75 years) must have platinum/PD- (L)1-refractory, HER2-positive (IHC 3+/2+) metastatic urothelial carcinoma with measurable lesions (RECIST v1.1), ECOG 0-1, and adequate organ function. Exclusions involve prior ADC/taxane therapy (&le;4 weeks), uncontrolled effusions/CNS metastasis, active infections, severe comorbidities, autoimmune diseases requiring immunosuppression, or investigator-deemed risks. Prior treatment toxicities must resolve to &le;Grade 1 (excluding alopecia/asymptomatic lab abnormalities).