Inclusion criteria: Adults (&ge;18) with ECOG 0-1, adequate organ function, and measurable lesions (RECIST 1.1), stratified by tumor type (Phase Ia: solid tumors; Phase Ib: G/GEJ AC, PDAC, BTC with CLDN18.2 positivity). Exclusions: recent anticancer therapy (<4 weeks), uncontrolled infections, major surgery (<4 weeks), CNS metastases, HIV/HBV/HCV, cardiovascular risks, bowel obstruction, or prior allogeneic transplants. Pregnancy and prior severe allergies to monoclonal antibodies are excluded.

The study evaluates safety through adverse events (AEs), treatment-emergent AEs (TEAEs), serious AEs (SAEs) assessed via NCI-CTCAE v5.0 over 90 days post-treatment, and dose-limiting toxicities (DLTs) monitored for 21 days post-first dose to determine MTD/RP2D. Efficacy is measured via investigator-assessed ORR per RECIST 1.1, tracking CR/PR rates over 2 years.

Pharmacokinetic parameters include Cmax, AUC, CL, t1/2, V, Tmax, and Ctrough of IBI343 over 2 years, alongside anti-drug antibody (ADA) incidence. Efficacy outcomes feature ORR, TTR (time to first CR/PR), DoR (response duration until PD/death), DCR (CR/PR/SD rates), PFS (time to progression/death), and OS (time to death from any cause) assessed over 2 years (OS: 1 year average).

Inclusion criteria: Adults (&ge;18) with ECOG 0-1, adequate organ function, and measurable lesions (RECIST 1.1), stratified by tumor type (Phase Ia: solid tumors; Phase Ib: G/GEJ AC, PDAC, BTC with CLDN18.2 positivity). Exclusions: recent anticancer therapy (<4 weeks), uncontrolled infections, major surgery (<4 weeks), CNS metastases, HIV/HBV/HCV, cardiovascular risks, bowel obstruction, or prior allogeneic transplants. Pregnancy and prior severe allergies to monoclonal antibodies are excluded.

The study evaluates safety through adverse events (AEs), treatment-emergent AEs (TEAEs), serious AEs (SAEs) assessed via NCI-CTCAE v5.0 over 90 days post-treatment, and dose-limiting toxicities (DLTs) monitored for 21 days post-first dose to determine MTD/RP2D. Efficacy is measured via investigator-assessed ORR per RECIST 1.1, tracking CR/PR rates over 2 years.

Pharmacokinetic parameters include Cmax, AUC, CL, t1/2, V, Tmax, and Ctrough of IBI343 over 2 years, alongside anti-drug antibody (ADA) incidence. Efficacy outcomes feature ORR, TTR (time to first CR/PR), DoR (response duration until PD/death), DCR (CR/PR/SD rates), PFS (time to progression/death), and OS (time to death from any cause) assessed over 2 years (OS: 1 year average).

Inclusion criteria: Adults (&ge;18) with ECOG 0-1, adequate organ function, and measurable lesions (RECIST 1.1), stratified by tumor type (Phase Ia: solid tumors; Phase Ib: G/GEJ AC, PDAC, BTC with CLDN18.2 positivity). Exclusions: recent anticancer therapy (<4 weeks), uncontrolled infections, major surgery (<4 weeks), CNS metastases, HIV/HBV/HCV, cardiovascular risks, bowel obstruction, or prior allogeneic transplants. Pregnancy and prior severe allergies to monoclonal antibodies are excluded.

The study evaluates safety through adverse events (AEs), treatment-emergent AEs (TEAEs), serious AEs (SAEs) assessed via NCI-CTCAE v5.0 over 90 days post-treatment, and dose-limiting toxicities (DLTs) monitored for 21 days post-first dose to determine MTD/RP2D. Efficacy is measured via investigator-assessed ORR per RECIST 1.1, tracking CR/PR rates over 2 years.

Pharmacokinetic parameters include Cmax, AUC, CL, t1/2, V, Tmax, and Ctrough of IBI343 over 2 years, alongside anti-drug antibody (ADA) incidence. Efficacy outcomes feature ORR, TTR (time to first CR/PR), DoR (response duration until PD/death), DCR (CR/PR/SD rates), PFS (time to progression/death), and OS (time to death from any cause) assessed over 2 years (OS: 1 year average).

Inclusion: Adults (&ge;18) with CLDN18.2-positive unresectable/metastatic pancreatic adenocarcinoma (confirmed histopathology, measurable lesions per RECIST 1.1), ECOG 0-1, life expectancy &ge;12 weeks, adequate organ function. Prior systemic therapy allowed in Part 1 but prohibited in Part 2 (treatment-na&iuml;ve population). Exclusion: Recent anti-tumor therapy (within 4 weeks), CYP3A4 inhibitors (2 weeks/5 half-lives), untreated CNS metastases, gastrointestinal perforation/fistula (6 months), interstitial lung disease, prior topoisomerase inhibitor ADCs, pregnancy, or conditions contraindicating study participation. Palliative radiotherapy/surgery is permitted under specific conditions.

There are two parts in this study, Part1 (safe lead-in phase) and Part2 (extension phase). In part1, patients with CLDN18.2-positive advanced pancreatic adenocarcinoma who had or had not previously received systemic therapy will be enrolled. The starting dose of the AG regimen was albumin-paclitaxel 100mg / m2 combined with gemcitabine 800mg / m2 by intravenous infusion (Intravenous, IV) D1 and D8 Q3W. If none of the first 3 subjects at 6 mg / kg had DLT during the DLT observation period, the combined high dose AG regimen was attempted. The investigator will adjust the dose of IBI343 combination chemotherapy according to the previous safety results and determine the safety of the combination dose, then entering the Part 2.

Key inclusion criteria involve signing informed consent, confirmed unresectable locally advanced or metastatic G/GEJ adenocarcinoma, CLDN18.2-positive status, &ge;18 years old, ECOG PS 0-1, and progression after &ge;2 prior systemic therapies (including specific regimens). Exclusion covers HER2-positive disease, concurrent interventional trials, prior topoisomerase inhibitor-based ADCs, recent anticancer treatments (within 4 weeks/5 half-lives), and planned non-study therapies (excluding palliative radiotherapy).

Secondary endpoints consist of objective response rate (ORR), disease control rate (DCR), duration of response (DoR), time to response (TTR), and pharmacokinetic parameters like AUC, Cmax, Tmax, Ctrough, CL, and V. Additionally, immunogenicity assessments include incidence of anti-drug antibodies (ADA) and neutralizing antibodies (NAb), each evaluated within approximately 20 months.

Eligible participants must provide informed consent, have confirmed unresectable locally advanced/metastatic G/GEJ adenocarcinoma, CLDN18.2 positivity, ECOG PS 0-1, and adequate organ function. Exclusions cover active infections (HIV, HBV/HCV), uncontrolled comorbidities (cardiopulmonary, CNS metastases), recent major surgery/radiotherapy, immunosuppressive therapy, prior topoisomerase inhibitor ADCs, pregnancy, or conditions jeopardizing safety/study integrity. Specific thresholds apply for lab values (e.g., ANC &ge;1.5&times;10⁹/L, platelets &ge;100&times;10⁹/L) and disease stability (e.g., asymptomatic brain metastases &le;1.5 cm).

The primary endpoints include Objective Response Rate (ORR) assessed per RECIST v1.1 and safety evaluations such as Adverse Events (AE), Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), Serious Adverse Events (SAE), and clinical monitoring parameters (laboratory exams, physical exams, vital signs), all tracked over 24 months.