Abstract 3206: Cadonilimabplus chemotherapy as first-line treatment in PD-L1 negative advanced non-small cell lung cancer (LungCadX): a phase II study

Abstract Introduction: Immunotherapy against non-small-cell lung cancer (NSCLC) with PD-L1-negative remain an unmet need. Cadonilimab is a bispecific antibody that simultaneously targets programmed cell death receptor-1 and cytotoxic T lymphocyte-associated antigen-4. In this study, we aimed to assess the efficacy and safety of cadonilimab combined with chemotherapy for the first-line treatment of PD-L1-negative advanced NSCLC. Methods: LungCadX (NCT06424821) is a multi-center, open-label, single-arm, phase II study. Patients received 4 cycles cadonilimab 10 mg/kg every three weeks plus chemotherapy, followed by cadonilimab maintenance therapy. The primary endpoint was the 12-month progression-free survival (PFS) rate by investigator assessment per RECIST 1.1. Secondary endpoints included overall survival (OS), PFS, objective response rate (ORR), duration of response (DOR), disease control rate (DCR) and the safety. Blood samples were collected at C1D1 and C3D1 for biomarker analysis. The study utilized PredicineALERT, a liquid biopsy methylation assay, to profile DNA methylation profiles in circulating tumor DNA (ctDNA) and monitor disease response. Result: As of data cutoff on November 8, 2024, 56 patients were enrolled with a median age of 64 years old, and 47 (83.9%) of them had stage IV NSCLC. 46 patients had at least 1 post-baseline tumor assessment. At a median follow-up of 6.7 months (range, 3.3 -11.5 months), the investigator-assessed ORR was 60.9% (28/46), with a 80.9% ORR for squamous (17/21) and 40.9% for non-squamous (11/25), and disease control rate (DCR) was 100.0% (46/46). Of the 50 patients who received at least two cycles of treatment, treatment-related adverse events were reported in 45 (80.3%), with grade ≥3 TRAEs occurring in 27 (48.2%), serious TRAEs reported in 12 (21.4%). The most common adverse events included leukopenia, neutropenia, thrombocytopenia, and anemia. No treatment-related deaths were reported. We completed ctDNA methylation analysis on samples collected at C1D1 and C3D1 from 18 patients. Changes in methylation scores from baseline to C3D1 were correlated with the RECIST 1.1. Specifically, all nine patients with a partial response exhibited a decrease in the differentially methylated fragment (DMF) score. In contrast, two patients with stable disease showed a greater than 20% increase in the DMF score, indicative of methylation-based progression and suggesting potential treatment resistance. Conclusions: Our preliminary result showed that cadonilimab plus chemotherapy showed promising anti-tumor activity and manageable safety as first-line treatment in patients with PD-L1 negative advanced NSCLC and may potentially be a promising treatment option. The ctDNA analysis underscores the potential of monitoring treatment efficacy by utilizing cfDNA methylation dynamic profiles. Citation Format: Li Wang, Haoran Tang, Hang Dong, Chunxia Su. Cadonilimabplus chemotherapy as first-line treatment in PD-L1 negative advanced non-small cell lung cancer (LungCadX): a phase II study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3206.