Safety and Effectiveness of Ivonescimab and Docetaxel Compared to Standard Treatment in Advanced Non-Small Cell Lung Cancer Patients With Long-Term Benefit From First-Line Immunotherapy

What this Trial Is About

Researchers are evaluating the safety and effectiveness of combining Ivonescimab, a PD-1VEGF bispecific antibody, with docetaxel chemotherapy compared to standard treatment in patients with advanced non-small cell lung cancer NSCLC. This phase II randomized, open-label trial focuses on patients who have had long-term benefits from first-line immune checkpoint inhibitors but still show minimal residual disease as detected by circulating tumor DNA ctDNA. The study aims to develop precision-guided treatments to delay cancer progression by using molecular monitoring to guide therapy adjustments. Participants who test positive for ctDNA will receive an escalation treatment involving Ivonescimab administered intravenously every three weeks at 20 mgkg and docetaxel given intravenously every three weeks at 75 mgm, with possible dose adjustments for tolerance. Those continuing their original maintenance treatment, such as immunotherapy alone or combined with chemotherapy, form the standard treatment group. Treatment continues until clinical benefit ends, unacceptable toxicity occurs, 24 months of treatment are completed, or other protocol criteria are met. During the study, participants will undergo regular visits for imaging assessments, laboratory tests, and clinical evaluations to monitor disease status and treatment safety. Researchers will measure progression-free survival over three years as the primary outcome, along with overall survival, response rates, adverse events, quality of life, and ctDNA clearance. Safety monitoring continues up to 28 days after treatment ends, with follow-up extending to five years. The total participation duration varies based on treatment outcomes and follow-up periods.

ctDNA-MRD Guided Escalation of Ivonescimab and Docetaxel in Advanced NSCLC With Long-Term Responses to First-line Immunotherapy (CR1STAL-Adaptive)