Eligible patients (≥18 years) have platinum/anti-PD-1-refractory recurrent/metastatic head and neck squamous cell carcinoma with measurable lesions (RECIST v1.1), ECOG 0-1, and adequate organ function (LVEF≥50%). Excluded are those with ≥4 prior systemic therapies, active CNS metastasis, uncontrolled cardiovascular/bleeding disorders, HBV/HCV/HIV, interstitial lung disease, or recent live vaccines (30 days). Prior anti-tumor therapies within specified washout periods (chemotherapy 3 weeks, targeted therapy 2 weeks, immunotherapy 4 weeks) are prohibited. Strict contraception and negative pregnancy tests are required. The study prioritizes patient safety with rigorous exclusion criteria for comorbidities.

Eligible patients (18-75 years) have platinum/PD- (L)1-refractory metastatic nasopharyngeal carcinoma (Part A: ≥1 prior line; Part B: ≥2 prior lines including platinum, gemcitabine/taxanes) with measurable lesions (RECIST v1.1), ECOG 0-1, and adequate organ function (LVEF≥50%). Exclusions: grade≥2 neuropathy, active CNS metastases, recent anti-tumor therapy (chemotherapy/targeted therapy within 3 weeks; immunotherapy/radiotherapy within 4 weeks), uncontrolled comorbidities (cardiac, hypertension, diabetes, HBV/HCV/HIV), ILD, or strong CYP3A4 modulators. Strict contraception and negative pregnancy tests (72 hours) are required.

Secondary endpoints include investigator-assessed ORR, PFS (time to progression/death), DoR (response duration), DCR (CR/PR/SD rates), and OS (time to death), along with PK parameters (Cmax/AUClast for MRG003, total antibody, and MMAE over 30 days) and ADA immunogenicity incidence, all tracked until progression/discontinuation (24 months). Safety monitoring covers AEs (30 days post-treatment) and SAEs (45 days).

Eligible patients (18-75 years, ECOG 0-1) include Phase Ia (advanced solid tumors) and Phase Ib (EGFR+ colorectal, HNSCC, or nasopharyngeal cancer) with measurable lesions (RECIST v1.1) and adequate organ function. Exclusions: CNS metastasis, prior malignancies (exceptions apply), uncontrolled systemic/hepatic/cardiac diseases, active HIV, recent anti-tumor therapies/surgeries, high-risk ophthalmic/skin conditions, or pregnancy/breastfeeding. Contraception is mandatory for participants of childbearing potential.

Pharmacokinetic parameters (Cmax, AUClast) for MRG003, total antibody, and MMAE are analyzed through blood samples with descriptive statistics. Immunogenicity is monitored via anti-drug antibody (ADA) assessments. Phase Ib additionally tracks PFS, DoR, and OS over 24 weeks. Safety includes AE/SAE incidence per NCI-CTCAE v5.0 until 30 days post-treatment.

Eligible patients (18-75 years, ECOG 0-1) include Phase Ia (advanced solid tumors) and Phase Ib (EGFR+ colorectal, HNSCC, or nasopharyngeal cancer) with measurable lesions (RECIST v1.1) and adequate organ function. Exclusions: CNS metastasis, prior malignancies (exceptions apply), uncontrolled systemic/hepatic/cardiac diseases, active HIV, recent anti-tumor therapies/surgeries, high-risk ophthalmic/skin conditions, or pregnancy/breastfeeding. Contraception is mandatory for participants of childbearing potential.

Pharmacokinetic parameters (Cmax, AUClast) for MRG003, total antibody, and MMAE are analyzed through blood samples with descriptive statistics. Immunogenicity is monitored via anti-drug antibody (ADA) assessments. Phase Ib additionally tracks PFS, DoR, and OS over 24 weeks. Safety includes AE/SAE incidence per NCI-CTCAE v5.0 until 30 days post-treatment.

Eligible patients (≥18 years) have platinum/anti-PD-1-refractory recurrent/metastatic head and neck squamous cell carcinoma with measurable lesions (RECIST v1.1), ECOG 0-1, and adequate organ function (LVEF≥50%). Excluded are those with ≥4 prior systemic therapies, active CNS metastasis, uncontrolled cardiovascular/bleeding disorders, HBV/HCV/HIV, interstitial lung disease, or recent live vaccines (30 days). Prior anti-tumor therapies within specified washout periods (chemotherapy 3 weeks, targeted therapy 2 weeks, immunotherapy 4 weeks) are prohibited. Strict contraception and negative pregnancy tests are required. The study prioritizes patient safety with rigorous exclusion criteria for comorbidities.

Eligible patients (18-75 years) have platinum/PD- (L)1-refractory metastatic nasopharyngeal carcinoma (Part A: ≥1 prior line; Part B: ≥2 prior lines including platinum, gemcitabine/taxanes) with measurable lesions (RECIST v1.1), ECOG 0-1, and adequate organ function (LVEF≥50%). Exclusions: grade≥2 neuropathy, active CNS metastases, recent anti-tumor therapy (chemotherapy/targeted therapy within 3 weeks; immunotherapy/radiotherapy within 4 weeks), uncontrolled comorbidities (cardiac, hypertension, diabetes, HBV/HCV/HIV), ILD, or strong CYP3A4 modulators. Strict contraception and negative pregnancy tests (72 hours) are required.

Secondary endpoints include investigator-assessed ORR, PFS (time to progression/death), DoR (response duration), DCR (CR/PR/SD rates), and OS (time to death), along with PK parameters (Cmax/AUClast for MRG003, total antibody, and MMAE over 30 days) and ADA immunogenicity incidence, all tracked until progression/discontinuation (24 months). Safety monitoring covers AEs (30 days post-treatment) and SAEs (45 days).

Eligible patients (18-75 years, ECOG 0-1) include Phase Ia (advanced solid tumors) and Phase Ib (EGFR+ colorectal, HNSCC, or nasopharyngeal cancer) with measurable lesions (RECIST v1.1) and adequate organ function. Exclusions: CNS metastasis, prior malignancies (exceptions apply), uncontrolled systemic/hepatic/cardiac diseases, active HIV, recent anti-tumor therapies/surgeries, high-risk ophthalmic/skin conditions, or pregnancy/breastfeeding. Contraception is mandatory for participants of childbearing potential.

Pharmacokinetic parameters (Cmax, AUClast) for MRG003, total antibody, and MMAE are analyzed through blood samples with descriptive statistics. Immunogenicity is monitored via anti-drug antibody (ADA) assessments. Phase Ib additionally tracks PFS, DoR, and OS over 24 weeks. Safety includes AE/SAE incidence per NCI-CTCAE v5.0 until 30 days post-treatment.

Eligible patients (18-75 years, BMI≥17, ECOG 0-1) must have EGFR+ advanced solid tumors (NSCLC, SCCHN, NPC) with measurable lesions (RECIST v1.1), adequate organ function, and life expectancy ≥12 weeks. Exclusions: CNS metastasis, prior MMAE/MMAF ADC treatment, Grade ≥2 neuropathy, uncontrolled systemic/liver/cardiac diseases, active infections (HBV/HCV/HIV), interstitial lung disease, recent major surgery/transplants, pregnancy/breastfeeding, or investigator-assessed ineligibility. Contraception is mandatory for participants of childbearing potential.

The study identifies Maximum Tolerated Dose (MTD) within 21 days of the last patient's first dose in the MTD group, defined as the highest dose with <33% DLT occurrence. The Recommended Phase II Dose (RP2D) is determined based on safety, efficacy, and PK data over 12 months. Objective Response Rate (ORR) is evaluated per RECIST v1.1, measuring the proportion of patients achieving complete response (CR) or partial response (PR).

Secondary outcomes include Duration of Response (DOR), Disease Control Rate (DCR), Progression-Free Survival (PFS), and Overall Survival (OS), all tracked over 12 months. Immunogenicity is assessed via anti-drug antibody (ADA) incidence up to 90 days post-treatment. Safety monitoring covers Adverse Events (AEs) until 30 days and Serious Adverse Events (SAEs) until 90 days post-treatment. PK analysis includes drug concentration-time profiles.

Eligible patients (18-75 years) have platinum/PD- (L)1-refractory metastatic nasopharyngeal carcinoma (Part A: &ge;1 prior line; Part B: &ge;2 prior lines including platinum, gemcitabine/taxanes) with measurable lesions (RECIST v1.1), ECOG 0-1, and adequate organ function (LVEF&ge;50%). Exclusions: grade&ge;2 neuropathy, active CNS metastases, recent anti-tumor therapy (chemotherapy/targeted therapy within 3 weeks; immunotherapy/radiotherapy within 4 weeks), uncontrolled comorbidities (cardiac, hypertension, diabetes, HBV/HCV/HIV), ILD, or strong CYP3A4 modulators. Strict contraception and negative pregnancy tests (72 hours) are required.

Secondary endpoints include investigator-assessed ORR, PFS (time to progression/death), DoR (response duration), DCR (CR/PR/SD rates), and OS (time to death), along with PK parameters (Cmax/AUClast for MRG003, total antibody, and MMAE over 30 days) and ADA immunogenicity incidence, all tracked until progression/discontinuation (24 months). Safety monitoring covers AEs (30 days post-treatment) and SAEs (45 days).

Eligible patients (18-75 years, BMI&ge;17, ECOG 0-1) must have EGFR+ advanced solid tumors (NSCLC, SCCHN, NPC) with measurable lesions (RECIST v1.1), adequate organ function, and life expectancy &ge;12 weeks. Exclusions: CNS metastasis, prior MMAE/MMAF ADC treatment, Grade &ge;2 neuropathy, uncontrolled systemic/liver/cardiac diseases, active infections (HBV/HCV/HIV), interstitial lung disease, recent major surgery/transplants, pregnancy/breastfeeding, or investigator-assessed ineligibility. Contraception is mandatory for participants of childbearing potential.

The study identifies Maximum Tolerated Dose (MTD) within 21 days of the last patient's first dose in the MTD group, defined as the highest dose with <33% DLT occurrence. The Recommended Phase II Dose (RP2D) is determined based on safety, efficacy, and PK data over 12 months. Objective Response Rate (ORR) is evaluated per RECIST v1.1, measuring the proportion of patients achieving complete response (CR) or partial response (PR).

Secondary outcomes include Duration of Response (DOR), Disease Control Rate (DCR), Progression-Free Survival (PFS), and Overall Survival (OS), all tracked over 12 months. Immunogenicity is assessed via anti-drug antibody (ADA) incidence up to 90 days post-treatment. Safety monitoring covers Adverse Events (AEs) until 30 days and Serious Adverse Events (SAEs) until 90 days post-treatment. PK analysis includes drug concentration-time profiles.

Eligible patients (18-75 years, ECOG 0-1) include Phase Ia (advanced solid tumors) and Phase Ib (EGFR+ colorectal, HNSCC, or nasopharyngeal cancer) with measurable lesions (RECIST v1.1) and adequate organ function. Exclusions: CNS metastasis, prior malignancies (exceptions apply), uncontrolled systemic/hepatic/cardiac diseases, active HIV, recent anti-tumor therapies/surgeries, high-risk ophthalmic/skin conditions, or pregnancy/breastfeeding. Contraception is mandatory for participants of childbearing potential.

Pharmacokinetic parameters (Cmax, AUClast) for MRG003, total antibody, and MMAE are analyzed through blood samples with descriptive statistics. Immunogenicity is monitored via anti-drug antibody (ADA) assessments. Phase Ib additionally tracks PFS, DoR, and OS over 24 weeks. Safety includes AE/SAE incidence per NCI-CTCAE v5.0 until 30 days post-treatment.

Eligible patients (18-75 years) had EGFR-positive, unresectable/metastatic biliary tract cancer refractory to &ge;1 prior therapy, with measurable lesions (RECIST v1.1), ECOG 0-1, and adequate organ function. Key exclusions included biliary obstruction, uncontrolled effusions/CNS metastasis, active infections, severe ocular/skin/pulmonary diseases, autoimmune disorders requiring immunosuppression, or prior anti-tumor therapy within 4 weeks. Treatment-related toxicities (except alopecia/asymptomatic labs) had to resolve to &le;Grade 1 (CTCAE v5.0). Pregnancy and decompensated cirrhosis (Child-Pugh B/C) were exclusionary.

Secondary efficacy endpoints included investigator-assessed ORR, Duration of Response (DoR), Time to Response (TTR), Disease Control Rate (DCR), Progression-Free Survival (PFS), and Overall Survival (OS). Safety assessments covered adverse events (30 days post-treatment), pharmacokinetic analysis of MRG003 (concentration-time curves), and incidence of anti-drug antibodies (ADA) in treated patients.

Eligible patients (18-75 years) have EGFR+/HER2- locally advanced/metastatic gastric adenocarcinoma with measurable lesions (RECIST v1.1), ECOG 0-1, adequate organ function (LVEF&ge;50%), and negative pregnancy tests. Exclusions: prior EGFR-targeted therapy hypersensitivity (4 weeks), active CNS metastasis, uncontrolled effusions/hemorrhage, severe infections (HBV/HCV/HIV), interstitial lung disease, Child-Pugh B/C cirrhosis, live vaccines (30 days), or grade&ge;2 peripheral neuropathy (CTCAE v5.0). Systemic anti-tumor therapy within 4 weeks or CYP3A4 modifiers prohibited.

Eligible patients (18-75 years) must have PD-1/platinum-refractory metastatic head and neck squamous cell carcinoma (&le;2 prior lines), measurable lesions (RECIST v1.1), ECOG 0-1, and adequate organ function (LVEF&ge;50%). Exclusions: grade&ge;2 neuropathy, active CNS metastases, recent anti-tumor therapy (chemotherapy within 3 weeks; immunotherapy within 4 weeks), uncontrolled comorbidities (cardiac, hypertension, diabetes, HBV/HCV/HIV), recent major surgery, or effusions requiring monthly drainage. Strict contraception and pregnancy testing are mandatory.

Secondary endpoints include Progression-Free Survival (PFS), Objective Response Rate (ORR), Disease Control Rate (DCR), Duration of Response (DOR), Treatment-Related Adverse Events (TRAEs), general Adverse Events (AEs), Serious Adverse Events (SAEs) with 30-90-day monitoring, and Quality of Life (QOL) assessments per RECIST v1.1, all tracked over 24 months.

Eligible patients (18-75 years) must have CDKN2A-deficient, PD-1/platinum-refractory recurrent/metastatic HNSCC (&le;2 prior lines), measurable lesions by RECIST v1.1, ECOG 0-1, and adequate organ function. Key exclusions: active CNS metastases, recent anti-cancer therapies (chemotherapy <3 weeks, immunotherapy <4 weeks), uncontrolled comorbidities (cardiac, HBV/HCV, HIV), uncontrolled effusions, or grade&ge;2 neuropathy. Pregnancy testing and contraception are mandatory.

Eligible patients (18-70 years, ECOG 0-1) must have untreated, surgically resectable EGFR+ HNSCC (Stage III-IVB non-oropharyngeal or Stage II-III HPV+ oropharyngeal cancer). Key exclusions: prior HNSCC treatment, active infections (HBV/HCV/HIV), grade&ge;2 neuropathy, recent major surgery/immunotherapy, uncontrolled cardiovascular disease, autoimmune disorders requiring immunosuppressants, or history of interstitial lung disease/allogeneic transplants. Adequate organ function and contraception are required.

Eligible patients (&ge;18 years, ECOG 0-1) must have EGFR+ advanced NSCLC (post &ge;2 prior therapies) with measurable lesions (RECIST v1.1), adequate organ function, and controlled AEs (&le;Grade 1 per CTCAE v5.0). Key exclusions: untreated CNS metastasis, active infections (HBV/HCV/HIV), severe cardiac/pulmonary disease (ILD, COPD), unresolved effusions, ongoing immunosuppressive therapy, prior EGFR-related eye/skin toxicities, or allogeneic transplants. Contraception is mandatory for patients of childbearing potential. Investigators may exclude patients with conditions compromising safety or compliance.

Secondary endpoints include Progression-Free Survival (PFS), Duration of Response (DoR), Time to Response (TTR), Disease Control Rate (DCR) (CR+PR+SD), and Overall Survival (OS), all measured over 12 months. Safety assessments involve monitoring Adverse Events (AEs) from baseline until 60 days post-treatment, including reactions, side effects, or any clinical trial events, regardless of drug-related causality.

Patients with advanced or metastatic solid tumors who had failed outcomes from or were not able to receive standard treatment were enrolled in phase 1a without EGFR prescreening. Phase 1b recruited EGFR-positive patients with refractory advanced squamous cell carcinomas of the head and neck (SCCHN), nasopharyngeal carcinoma (NPC), and colorectal cancer (CRC).

The objective response rates for SCCHN, NPC, and CRC were 40.00%, 44.00%, and 0.00%, and the disease control rates were 100.00%, 89.00%, and 25.00%, respectively. The median DOR of all patients was 5.60 months (SCCHN: DOR, 5.60 months; 95% CI,2.80-5.60; NPC: not estimable). The median PFS of all patients was 2.80 months (95% CI,1.20-4.10 months), and the PFS of SCCHN, NPC, and CRC was 2.80 (95% CI,0.60-6.80) months, 4.00 (95% CI, 1.20-not reached) months, and 1.20 (95% CI, 0.50-2.80) months, respectively. SCCHN cohort reached the median OS as of the data cutoff date, which was 11.80 (95% CI, 3.40-11.80) months.