Cadonilimab as second-line therapy in immunotherapy-resistant squamous NSCLC: a case report and review

Abstract

Immune checkpoint inhibitors (ICIs) have become a pivotal therapeutic option for the treatment of advanced non-small cell lung cancer (NSCLC), particularly as a standard first-line therapy. However, most patients eventually develop resistance to ICIs, and the options for second-line treatment remain limited with suboptimal efficacy. Cadonilimab, a novel bispecific antibody targeting programmed death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), has demonstrated promising antitumor activity with a manageable safety profile. Nevertheless, its clinical efficacy in patients who have developed resistance to prior immunotherapy remains largely unexplored. This report presents a case of an elderly patient with early-stage NSCLC who developed resistance following first-line immunotherapy. After receiving subsequent treatment with cadonilimab, the patient achieved a partial response (PR) at the third cycle. The patient experienced substantial clinical improvement, including marked relief from chest tightness and shortness of breath, as evidenced by a reduction in modified Medical Research Council (mMRC) dyspnea grade from 3 to 1. The quality of life improved significantly, as indicated by a rise in the Karnofsky Performance Status (KPS) score from 60 to 80. Progression-free survival (PFS) was extended to 17 months, and the patient continues to derive clinical benefit. No immune-related adverse events (irAEs) affecting daily life occurred throughout the entire course of therapy. These findings suggest that cadonilimab may serve as a promising subsequent-line therapeutic option for patients with immunotherapy resistance.

Keywords: PD-1/CTLA-4 bispecific; case report; immunotherapy; immunotherapy resistance; squamous non-small cell lung cancer.

Figure 1

Representative baseline diagnostic assessments prior to treatment initiation. (A, B) Contrast-enhanced chest CT demonstrated a space-occupying lesion in the right lower hilar region, accompanied by obstructive pneumonia. (C) Bronchoscopic examination revealed an endobronchial mass causing luminal obstruction of the dorsal segment of the right lower lobe. (D) Histopathological analysis with hematoxylin and eosin (H&E) staining confirmed poorly differentiated squamous cell carcinoma (original magnification, ×100). (E) Immunohistochemical staining revealed PD-L1 expression with a tumor proportion score (TPS) of 55%.

Figure 2

(A) Representative PET/CT imaging during pembrolizumab therapy. (a) PET/CT performed on April 7, 2021, showed a marked reduction in the size of the right lower lobe lesion compared to baseline (Figure 1A). (b) PET/CT conducted on March 31, 2022, demonstrated significant progression of the lesion in the right lower lobe relative to image (A, B) Serial contrast-enhanced chest CT scans before and after radiotherapy. (a) CT scan obtained on November 21, 2022, prior to radiotherapy. (b) CT scan performed on February 20, 2023, approximately six weeks post-radiotherapy completion, indicating complete response (CR).

Figure 3

(A) Radiographic evaluation of cadonilimab as second-line therapy following disease progression on pembrolizumab. (a) Chest CT performed on October 16, 2023, prior to initiating cadonilimab. (b) Chest CT conducted on December 11, 2023, after three cycles of cadonilimab. (c) Chest CT obtained on March 6, 2025, following 22 cycles of cadonilimab therapy. (B) A transient and mild elevation in serum high-sensitivity cardiac troponin T (hs-cTnT) levels was observed during treatment(reference range: 0–0.014 μg/L).

Figure 4

The treatment timeline for the patient. From December 28, 2020, to March 31, 2022, the patient received pembrolizumab therapy. Following disease progression, cadonilimab was initiated on January 22, 2024.