Phase I secondary: DLTs [28 days]; safety profile (AEs/SAEs ≥Grade 3 per CTCAE v5.0) [treatment+30 days]; preliminary efficacy (ORR/DOR/PFS/OS) [12 months]; ADA formation [6 cycles]; PK parameters (SKB264-ADC/TAB/free payload) [6 cycles]. Phase II secondary: safety profile; efficacy (DOR/PFS/OS) [12 months]; ADA formation; PK parameters; TROP2 expression correlation [screening to EOT].

Histologically confirmed advanced/metastatic gastric/GEJ/esophageal adenocarcinoma; measurable disease per RECIST 1.1; progressed on ≥2 prior regimens; HER2 status-independent (HER2+ must have prior trastuzumab); adequate organ function; tumor tissue for TROP2 assessment; recovered toxicities (≤Grade 1); ECOG 0-1; controlled HIV/HBV/HCV permitted; oral medication ability.

Eligible participants had histologically confirmed advanced/metastatic non-squamous NSCLC with specific mutations, RECIST 1.1 progression after prior therapy (EGFR TKI + platinum-based therapy for mutated cases), measurable disease, and available tumor tissue. Required criteria: recovery from prior therapy AEs (Grade ≤1), controlled HBV/HIV if applicable, and ECOG performance status 0-1 within 3 days pre-randomization.

Progression-free Survival (PFS) in NSCLC patients with EGFR mutations was assessed up to 35 months, defined as time from randomization to first disease progression per RECIST 1.1 (BICR) or death. Overall Survival (OS) in this cohort was measured up to 41 months as time from randomization to death. For all NSCLC participants, PFS (up to 35 months) and OS (up to 41 months) were similarly defined. Objective Response Rate (ORR) in EGFR-mutated NSCLC (up to 35 months) and all NSCLC participants (up to 35 months) was the percentage achieving Complete Response (CR: disappearance of target lesions) or Partial Response (PR: ≥30% decrease in target lesion diameters) per RECIST 1.1 (BICR). Duration of Response (DOR) in all NSCLC participants (up to 6 years) was time from first CR/PR to progression/death.

Quality of Life metrics included changes from baseline in EORTC QLQ-C30 scores (Global Health Status/QoL [Items 29-30], Dyspnea [Item 8]) and QLQ-LC13 scores (Cough [Item 31], Chest Pain [Item 40]) up to 48 weeks, with higher scores indicating better QoL for Global Health but worse symptoms for others. Time to Deterioration (TTD) was defined as first ≥10-point score decline (confirmed by subsequent ≥10-point drop) in Global Health Status/QoL, Dyspnea, Cough, and Chest Pain scores up to 48 weeks. Safety outcomes included number of participants with ≥1 Adverse Event (AE) (up to 6 years) and treatment discontinuations due to AEs (up to 4 years).

Progression-free survival (PFS) was defined as time from randomization to first documented disease progression per RECIST 1.1 (BICR) or death (up to 48 months). Objective Response (OR) required confirmed CR/PR per RECIST 1.1 (BICR), with Duration of Response (DOR) measuring time from first CR/PR to progression/death. Quality of Life assessments included EORTC QLQ-C30 (Items 29/30: 7-point scale for GHS/QOL; Item 8: 4-point dyspnea scale) and QLQ-LC13 (Items 31/40: 4-point scales for cough/chest pain), with Time to Deterioration (TTD) analyzed for each (baseline to 24 months). Safety outcomes covered AE rates (27 months) and treatment discontinuations due to AEs (24 months).

Objective Response Rate (ORR) required confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in sum of target lesion diameters) per RECIST 1.1 (BICR). Duration of Response (DOR) measured time from first CR/PR to progression/death. Quality of Life assessments included EORTC QLQ-C30 (Items 29/30: 7-point GHS/QOL scale; Item 8: 4-point dyspnea scale) and QLQ-LC13 (Items 31/40: 4-point scales for cough/chest pain), with Time to Deterioration (TTD) defined as ≥10-point score decrease (baseline to 6 years). Safety outcomes covered AE incidence and treatment discontinuations (up to 6 years).

Participants will receive pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) for up to 12 weeks + double-platinum chemotherapy per neoplasm histology classification at the investigator's discretion as neoadjuvant therapy prior to surgery; followed by sacituzumab tirumotecan 4 mg/kg IV infusion every 2 weeks (Q2W) for up to 12 doses (~24 weeks) with pembrolizumab monotherapy 200 mg IV infusion every 6 weeks (Q6W) for up to 7 cycles (~42 weeks).

Overall Survival (OS) measured time to death (up to 118 months). Secondary endpoints included Distant Metastasis-Free Survival (DMFS; time to first distant metastasis/death), investigator-assessed DFS, and Lung Cancer-Specific Survival (LCSS). Safety outcomes covered AE incidence and treatment discontinuations. Quality of Life was evaluated via EORTC QLQ-C30 (GHS/QoL, physical/role functioning, dyspnea) and QLQ-LC24 (cough, chest pain) scales (0-100; higher scores indicate better function except symptom scales).

Secondary endpoints encompass safety outcomes (adverse event incidence over 5 years, treatment discontinuations within 1 year, and perioperative complications within 20 weeks), efficacy measures (event-free survival, overall survival, and distant metastasis-free survival over 5 years, plus objective response rate at 12 weeks), and surgical parameters (hospitalization duration, readmission rates, operative time, and transfusion requirements within 20 weeks).

Eligible participants must be aged 18-75 with histologically confirmed NSCLC, stratified into three cohorts: Cohort 1 (EGFR/ALK wild-type, ≤1 prior chemotherapy line), Cohort 2 (EGFR/ALK wild-type, treatment-naïve), and Cohort 3 (EGFR-mutant, EGFR-TKI failures). Additional criteria include provision of tumor tissue for biomarker analysis, ≥1 measurable lesion (excluding skin/bone-only disease), ECOG 0-1, life expectancy ≥12 weeks, adequate organ function, and agreement to use contraception during and for 6 months post-treatment. All patients must provide informed consent and comply with protocol requirements.

The primary endpoints include safety evaluation through incidence and severity of adverse events (AEs) graded by CTCAE v5.0, assessed from baseline up to 30 days after the last dose or until initiation of new anti-cancer therapy (up to 24 months), as well as efficacy measured by Objective Response Rate (ORR), defined as the percentage of participants achieving Complete Response (CR) or Partial Response (PR) per RECIST v1.1 criteria, evaluated from baseline to the first documented response (up to 24 months).

Secondary endpoints comprise Progression-Free Survival (PFS), defined as time from baseline to disease progression or death (up to 24 months); Duration of Response (DOR), measuring time from first response to progression or death in responders only (up to 24 months); Disease Control Rate (DCR), combining CR, PR, and Stable Disease (SD) rates per RECIST v1.1 (up to 24 months); pharmacokinetic parameters (Cmax and Cmin) for SKB264-ADC, SKB264-TAB, free KL610023, and KL-A167, assessed during Cycles 1-8 and every 4 cycles thereafter (up to 24 months); and Anti-Drug Antibodies (ADA) for SKB264 and KL-A167, evaluated similarly.

Eligible subjects must be ≥18 years with histologically confirmed locally advanced/metastatic NSCLC, either EGFR wild-type/ALK-negative (treatment-naïve or with ≤1 prior therapy) or EGFR-mutant (TKI-naïve or TKI-resistant), able to provide tumor samples, have ≥1 measurable lesion per RECIST v1.1, ECOG 0-1, ≥3-month life expectancy, adequate organ function, recovery from prior treatment toxicities, compliance with contraceptive requirements, and willingness to sign informed consent and adhere to protocol procedures.

The study evaluates safety and tolerability through dose-limiting toxicity (DLT), incidence/severity of adverse events (AEs), and treatment discontinuation due to AEs, assessed from informed consent until 30 days post-treatment (up to 36 months), while efficacy is measured by objective response rate (ORR) per RECIST v1.1, defined as the proportion of subjects achieving complete (CR) or partial response (PR) during the study period (up to 36 months).

Key secondary endpoints include duration of response (DOR) for responders (time from first CR/PR to progression/death), progression-free survival (PFS) (time from treatment initiation to progression/death), and overall survival (OS) (time from treatment start to death from any cause), all evaluated over approximately 36 months using radiographic assessments and clinical follow-up.

Eligible participants must be 18-75 years old with histologically confirmed stage IIIB/IIIC/IV non-squamous NSCLC harboring EGFR-sensitive mutations after EGFR-TKI failure, have ≥1 measurable lesion per RECIST 1.1, ECOG 0-1, ≥12-week life expectancy, adequate organ function, use effective contraception, and voluntarily comply with study procedures through signed informed consent.

The study evaluates efficacy through progression-free survival (PFS) assessed by both blinded independent review committee (BIRC) and investigators per RECIST 1.1, measured from baseline until disease progression or death (up to 36 months), along with overall survival (OS) from randomization to death (up to 2 years), objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and time to response (TTR) - all assessed by investigators and BIRC per RECIST 1.1 within 2 years.

Safety assessments include incidence/severity of adverse events (AEs) and serious adverse events (SAEs) per CTCAE 5.0 from informed consent until 30 days post-treatment, while quality of life is measured through changes in EORTC QLQ-C30 and QLQ-LC13 questionnaires over 2 years to evaluate disease-related symptoms and health-related quality of life impact.

Eligible participants must be aged 18-75 with histologically confirmed treatment-naïve stage IIIB-IV non-squamous NSCLC harboring EGFR-sensitive mutations, have ≥1 measurable lesion per RECIST v1.1, ECOG PS 0-1, ≥12-week life expectancy, available tumor samples, and adequate organ function, ensuring a well-defined patient population for this clinical investigation.

Secondary endpoints include overall survival (OS) assessed up to 49 months, investigator-evaluated PFS (36 months), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), and time to response (TTR) - all measured by both BICR and investigators per RECIST 1.1 standards over 36 months, providing comprehensive efficacy evaluation across multiple dimensions.

Eligible patients (18-75 years) must have histologically confirmed NSCLC (with specific EGFR/ALK status requirements per cohort) or nasopharyngeal carcinoma, disease progression after prior therapies (including EGFR-TKIs, platinum chemotherapy, or PD-1/L1 inhibitors where applicable), ≥1 measurable lesion, ECOG 0-1, ≥12-week life expectancy, adequate organ function, and willingness to provide tumor tissue samples and comply with contraceptive requirements during and for 6 months post-treatment.

The primary efficacy endpoint is objective response rate (ORR), defined as the proportion of patients achieving complete response (CR) or partial response (PR) per RECIST 1.1 criteria, assessed from baseline until disease progression or death (up to 21 months). Safety will be evaluated through incidence and severity of adverse events (graded by CTCAE v5.0) monitored from informed consent through 30 days post-treatment.

Secondary endpoints include progression-free survival (PFS), duration of response (DOR), and disease control rate (DCR) - all assessed per RECIST 1.1 over 21 months - along with overall survival (OS) until death. Pharmacokinetic parameters (Cmax/Cmin of SKB264-ADC, SKB264-TAB and free KL610023) and immunogenicity (anti-drug antibodies) will be evaluated for 12 months post-enrollment to characterize drug exposure and potential immune responses.

Eligible participants must have ECOG performance status 0-1, ≥3 month life expectancy, and measurable disease per RECIST 1.1 across five cancer cohorts: recurrent/metastatic cervical cancer (Cohort A), advanced urothelial carcinoma (Cohort B), recurrent ovarian cancer (Cohort C), metastatic prostate cancer (Cohort D), and advanced endometrial cancer (Cohort E). Additional requirements include providing tumor samples for biomarker analysis, adequate organ function, recovery from prior treatment toxicities (excluding non-safety concerns), compliance with contraception guidelines, and ability to provide informed consent.

The study evaluates safety through dose-limiting toxicities (DLTs) and adverse events (AEs) graded by CTCAE v5.0 from informed consent through 30 days post-treatment, while efficacy is assessed via objective response rate (ORR) per RECIST 1.1 (confirmed CR/PR) and, for prostate cancer patients (Cohort D), PSA response rate (≥50% decrease confirmed ≥3 weeks apart), both measured from baseline until progression/death (up to 21 months).

Eligible participants must have histologically confirmed locally advanced/metastatic urothelial carcinoma (la/mUC) with evaluable tumor tissue. Part 1 requires prior platinum chemotherapy (≤2 lines; avelumab maintenance counts as one line), while Part 2 excludes prior systemic therapy for la/mUC. All subjects must have recovered from prior treatment toxicities (≤Grade 1) and meet standard organ function requirements.

The study evaluates safety through dose-limiting toxicities (DLTs) and adverse events (AEs) graded by CTCAE v5.0 in both Part 1 (up to 3 years) and Part 2 (up to 2 years), including treatment discontinuations due to AEs. Efficacy is assessed via objective response rate (ORR) per RECIST 1.1 (confirmed CR/PR) in Part 2 (up to 3 years), with DLTs specifically monitored during the first 21 days of each part.

Secondary endpoints include pharmacokinetic parameters (Cmax/Ctrough of sacituzumab tirumotecan-ADC, free payload, enfortumab vedotin-ADC, and pembrolizumab-ADC) measured through serial blood sampling across treatment cycles (up to Cycle 35), along with immunogenicity (antidrug antibody incidence) for all study drugs. Part 1 additionally evaluates ORR, while Part 2 assesses duration of response (DOR) from first CR/PR to progression/death per RECIST 1.1.

Pharmacokinetic analysis of sacituzumab tirumotecan (sac-TMT) includes serum/plasma measurements (AUC, Cmax, Cmin, half-life) for both ADC and free payload over 6 weeks, with efficacy endpoints assessing complete response rate (CRR) by cystoscopy/cytology within 6 months and duration of response (DCR) tracking recurrence-free survival up to 24 months.

Eligible patients ≥18 years with progressive advanced solid tumors after prior therapy, adequate organ function and measurable disease. Key exclusions: prior Top1-ADC therapy, CNS metastases, major cardiac disease, recent systemic therapy/surgeries, ocular disorders, or active skin conditions requiring treatment. Both genders must comply with contraception requirements.