Lung Non-Small Cell Squamous Cancer

P2, N=74, Not yet recruiting, Università Vita-Salute San Raffaele

In terms of OS, pembrolizumab + chemotherapy + canakinumab (Pembro-chemo-canakinumab) (SUCRA =0.90) showed great potential in improving outcomes, although its long-term efficacy still needed to be validated...For squamous patients, nivolumab + ipilimumab ± chemotherapy (Nivo-ipi-chemo) led in OS, while serplulimab + chemotherapy in PFS. First-line personalized treatment for PD-L1 <1%, advanced NSCLC should be histology-based, balancing efficacy and toxicity. Pembro-chemo and nivolumab + chemotherapy + bevacizumab combinations are recommended as the optimal first-line options for non-squamous patients, and Nivo-ipi-chemo for squamous patients.

P2, N=104, Not yet recruiting, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

P3, N=160, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

P3, N=327, Recruiting, UNICANCER | Active, not recruiting --> Recruiting | Trial completion date: Jul 2027 --> Dec 2026 | Trial primary completion date: Jan 2026 --> Dec 2026

P2, N=102, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

We report a unique case of a 65-year-old man with squamous-cell NSCLC and high PD-L1 expression (80%), who developed a rare complication: radiation recall pneumonitis (RRP), with superimposed Pneumocystis jirovecii pneumonia and severe symptomatic hyponatremia induced by trimethoprim/sulfamethoxazole (TMP-SMX). The coexistence of these three complications-radiotherapy- and immunotherapy-associated lung injury, opportunistic infection, and electrolyte imbalance-represents an exceptional clinical scenario not previously described in the literature. This report highlights the importance of differential diagnosis, early recognition of complications, and close monitoring of electrolytes in NSCLC patients undergoing complex treatment regimens.

P=N/A, N=212, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed | N=350 --> 212

P1/2, N=288, Active, not recruiting, BicycleTx Limited | Recruiting --> Active, not recruiting | Trial completion date: Oct 2025 --> Jul 2027 | Trial primary completion date: Oct 2025 --> Jul 2026

P1/2, N=22, Completed, Laekna Limited | Active, not recruiting --> Completed

In patients receiving first-line paclitaxel/nab-paclitaxel-platinum combined with anti-programmed cell death-1 (PD-1)/PD-L1 antibodies, FGFR2b-positive cohorts exhibited superior outcomes: higher objective response rate (57.4% vs. 41.9%) and prolonged median progression-free survival {11.3 months [95% confidence interval (CI): 6.6-17.9] vs. 6.5 months (95% CI: 5.0-17.3)} compared to FGFR2b-negative counterparts. FGFR2b expression may serve as a predictive biomarker for therapeutic response of FGFR2b-targeted agents in sqNSCLC. The high co-expression rate of FGFR2b and PD-L1 supports the feasibility of combining FGFR2b-targeted agents with immune checkpoint inhibitors as a rational treatment strategy.

A genomic expression analysis performed in Cohort #3 (n = 35) showed that a downregulation in the PI3K/AKT/mTOR pathway was mainly evident in the GP group of patients. This integrated multi-step analysis identified potentially altered pathways with a biological impact on squamous-NSCLC oncogenesis, suggesting that the PI3KCA/mTOR pathway could affect the prognosis of resected SCC patients through both genomic aberrations and impaired expression.