Study design and rationale for the NeoTRACE trial: a multicenter phase II study of neoadjuvant sacituzumab govitecan plus zimberelimab followed by adjuvant zimberelimab with or without sacituzumab govitecan in patients with resectable non-small cell

Perioperative chemoimmunotherapy improves pathological complete response (pCR), EFS, and OS in patients with resectable NSCLC versus chemotherapy, as shown in several phase-III-trials. However, approximately 17-22% of patients did not proceed to surgery, partly due to toxicity, highlighting the need for more efficacious and tolerable regimens. NeoTRACE is a phase II, multicenter, single-arm study to evaluate neoadjuvant sacituzumab govitecan (SG) and the PD-1 inhibitor zimberelimab (ZIM) in resectable stage II to IIIB (N2) NSCLC with no known EGFR/ALK alterations. The trial plans to enroll 50 participants, with neoadjuvant treatment administered for four cycles before resection, followed by adjuvant ZIM with/without SG at the physicians' discretion. The primary endpoint is the rate of pCR in tumor and lymph nodes. Secondary endpoints include major pathological response, surgical resection rate, disease-free survival, OS, safety, and quality of life. The study also explores circulating tumor DNA (ctDNA) dynamics, TROP2 expression, and spatial transcriptomics to identify biomarkers. NeoTRACE assesses a platinum-sparing approach in resectable NSCLC. Previous studies showed ADC and immunotherapy combinations are effective in advanced NSCLC, suggesting potential perioperative benefit. This study aims to improve pCR rate, reduce toxicity, enhance surgical eligibility, and personalize adjuvant treatment to improve long-term outcomes.<b>Clinical Trial Registration</b>: EudraCT: 2024-517561-16.