This is a single-arm, multi-center phase II study to evaluate the efficacy and safety of sacituzumab tirumotecan (Sac-TMT/SKB264) combined with tagitanlimab (KL-A167) as 2nd line therapy for recurrent or metastatic esophageal squamous cell carcinoma (ESCC) or gastric/gastroesophageal junction adenocarcinoma (G/GEJA). A total of 75 participants are planned to be enrolled with 10 in the safety lead-in phase and 33 ESCC and 42 G/GEJA in expansion phase, seperately.
Aged ≥18 years at the time of signing the informed consent form;
Histologically or cytologically confirmed diagnosis of unresectable locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) or gastric/gastroesophageal junction (GEJ) adenocarcinoma;
Esophageal squamous cell carcinoma (ESCC) and gastric/gastroesophageal junction (GEJ) adenocarcinoma with disease progression following first-line anti-PD-1 combined chemotherapy, and the progression-free survival (PFS) of first-line treatment ≥3 months;
Radical concurrent chemoradiotherapy, neoadjuvant or adjuvant therapy: disease progression occurring during treatment or within 6 months after treatment discontinuation shall be deemed failure of first-line treatment.
Participants diagnosed with other malignant tumors within 3 years prior to study drug administration, except for tumors cured by local therapy (e.g., basal cell carcinoma of the skin, cutaneous squamous cell carcinoma, cervical carcinoma in situ, etc.);
Participants with known meningeal metastasis, brainstem metastasis, spinal cord metastasis and/or spinal cord compression, or active central nervous system (CNS) metastases without prior local treatment. Participants with previously locally treated brain metastases may be enrolled if they remain clinically stable for at least 4 weeks prior to the first dose and do not require corticosteroids or anticonvulsants for a minimum of 14 days;
Severe or uncontrolled cardiac disorders or clinical symptoms requiring treatment within 6 months before the first study dose, including New York Heart Association (NYHA) Class III or IV congestive heart failure, drug-refractory unstable angina, severe arrhythmias requiring pharmacotherapy (excluding atrial fibrillation or paroxysmal supraventricular tachycardia), and myocardial infarction;
Prior history of myocarditis or cardiomyopathy;