JS212 in Combination With JS111 as First-Line Treatment in EGFR-Mutant Advanced NSCLC

This is a single-arm clinical study designed to evaluate the safety, tolerability, and preliminary antitumor activity of JS212 in combination with JS111 as first-line treatment in participants with EGFR-mutant locally advanced or metastatic NSCLC who have not previously received systemic therapy for EGFR-mutant advanced disease. Participants will receive JS212 by intravenous infusion on Day 1 once every 3 weeks (Q3W), in combination with JS111 at 160 mg administered orally once daily (QD). Each treatment cycle is 21 days. Study treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or another protocol-defined treatment discontinuation criterion is met. The study includes two sequential stages: a safety lead-in stage and a clinical expansion stage. Approximately 20 participants are planned to be enrolled in total, although the final sample size may be adjusted by the Safety Monitoring Committee based on accumulating safety, tolerability, and efficacy data. Safety Lead-in Stage Up to 10 participants will be enrolled in the safety lead-in stage. The first 21 days following the initial administration of JS212 and JS111 will constitute the significant toxicity observation period. The SMC will review the accumulated data and determine the JS212 dose to be used in combination with JS111 during the clinical expansion stage. Before study initiation or during study conduct, the SMC may also consider emerging safety, tolerability, pharmacologic, and efficacy data from other ongoing studies of JS212 administered as monotherapy or in combination with other agents. Based on these data, the SMC may recommend modification of the JS212 dose, evaluation of another dose level, or omission of the safety lead-in stage and direct initiation of the clinical expansion stage, as specified in the SMC Charter. Clinical Expansion Stage After review of the safety lead-in data, participants enrolled in the clinical expansion stage will receive the SMC-selected dose of JS212 in combination with JS111 at 160 mg QD. The clinical expansion stage will further characterize the safety, tolerability, and preliminary antitumor activity of the combination. Treatment will be administered in 21-day cycles and will continue until disease progression, unacceptable toxicity, withdrawal of consent, or another protocol-defined treatment discontinuation criterion is met. The study is expected to enroll approximately 20 participants in total across the safety lead-in and clinical expansion stages. The SMC may adjust the number of participants based on emerging study data. Study Objectives The primary objective is to evaluate the safety and tolerability of JS212 in combination with JS111 and to determine the JS212 dose to be further evaluated in combination with JS111. The secondary or exploratory objective is to evaluate the preliminary antitumor activity of JS212 in combination with JS111 as first-line treatment in participants with EGFR-mutant locally advanced or metastatic NSCLC.