A Study to Evaluate the Safety, Pharmacokinetics and Efficacy of TJ101 in Patients With Advanced/Metastatic Solid Tumors

This is a first-in-human, Phase I, open-label, multicenter study designed to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, and preliminary efficacy of TJ101, a bispecific antibody-drug conjugate (ADC) targeting EGFR and B7-H3, in patients with advanced or metastatic solid tumors. Study Objectives Phase Ia (Dose Escalation) * Primary: Assess safety/tolerability; determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended dose(s) for expansion (RDEs). * Secondary: Characterize PK profile, assess preliminary anti-tumor activity, and evaluate immunogenicity. Phase Ib (Dose Expansion) * Primary: Further assess safety and preliminary anti-tumor activity of TJ101 at the selected RDEs. * Secondary: Further characterize PK profile and immunogenicity. Study Design * Part 1: Dose Escalation (Phase Ia) * Up to 72 patients with advanced/metastatic solid tumors. * Six planned dose cohorts: IV every 3 weeks (Q3W). * Accelerated titration for first cohort; 3+3 design for subsequent cohorts. * Backfill cohorts (6-12 patients each) may be added at promising dose levels to refine safety, PK, and efficacy data. * DLT evaluation window: 21 days after first infusion (Cycle 1). * Safety Monitoring Committee (SMC) reviews all data to guide escalation, backfill, and RDE selection. Part 2: Dose Expansion (Phase Ib) * 40-180 patients, across tumor-specific cohorts * Patients randomized to 2-3 RDEs of TJ101. * 20-30 subjects per tumor type/dose level. * Expansion will refine safety/PK and assess anti-tumor activity in biomarker-selected subgroups. * Dosing: IV infusion on Day 1 of each 21-day cycle; continued until progression, unacceptable toxicity, withdrawal, or investigator decision. Study Procedures \& Monitoring * Screening: within 28 days prior to first dose. * Safety Monitoring: continuous AE collection, labs, vitals, ECOG, ECGs, ophthalmologic exams, skin checks. * Efficacy Assessments: imaging at baseline, then every 6 weeks (first 24 weeks), every 9 weeks thereafter, and every 12 weeks from year 2 until progression or new therapy. * PK/Immunogenicity Sampling: intensive during Cycles 1 and 3; serial sampling in later cycles. * Follow-up: * 30-day safety follow-up after last dose. * Survival follow-up every 3 months until death or study termination. Enrollment \& Duration * Estimated enrollment: up to 252 patients. * Study duration: \~ 2-3 years.