A Phase II Trial of Perioperative Camrelizumab Plus Neoadjuvant Chemotherapy in Resectable Stage IIB–IIIB Lung Squamous Cell Carcinoma

Abstract

This phase II trial investigated perioperative camrelizumab plus neoadjuvant chemotherapy for patients with stage IIB–IIIB lung squamous cell carcinoma (LUSC) and explored predictive biomarkers of treatment response. Patients received neoadjuvant camrelizumab (200 mg, Day 1) in combination with nab-paclitaxel (130 mg/m², Days 1 and 8) and carboplatin (area under the curve = 5, Day 1) every 3 weeks for two cycles, followed by surgery and adjuvant camrelizumab for 1 year. The primary endpoint was major pathological response (MPR) rate. Forty-five patients were treated, of whom 41 underwent surgery. Twenty-seven of 45 patients (60.0%) achieved MPR and 20 (44.4%) achieved pathological complete response (pCR). With a median follow-up of 37.5 months, the 3-year disease-free survival and overall survival rates were 65.9% and 68.7%, respectively. Among eight patients with stage IIIB disease, three (37.5%) achieved pCR. Baseline neutrophil percentage and smoking history were associated with MPR. T-cell receptor (TCR) sequencing revealed that three V-J gene pairs in TCR beta clones differed between the pCR and non-pCR groups. This study supports the application of perioperative immunotherapy combined with neoadjuvant chemotherapy in patients with resectable locally advanced LUSC. The identification of blood biomarkers for precise patient selection warrants further in-depth investigation.

Keywords

camrelizumab / lung squamous cell carcinoma / major pathological response / neoadjuvant immunochemotherapy / perioperative immunotherapy

References

[1] F. Bray, M. Laversanne, H. Sung, et al., “Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries,” CA: A Cancer Journal for Clinicians 74, no. 3 (2024): 229–263.

[2] A. G. Nicholson, M. S. Tsao, M. B. Beasley, et al., “The 2021 WHO Classification of Lung Tumors: Impact of Advances Since 2015,” Journal of Thoracic Oncology 17, no. 3 (2022): 362–387.

[3] P. M. Forde, J. Spicer, S. Lu, et al., “Neoadjuvant Nivolumab Plus Chemotherapy in Resectable Lung Cancer,” New England Journal of Medicine 386, no. 21 (2022): 1973–1985.

[4] H. Wakelee, M. Liberman, T. Kato, et al., “Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer,” New England Journal of Medicine 389, no. 6 (2023): 491–503.

[5] J. V. Heymach, D. Harpole, T. Mitsudomi, et al., “Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer,” New England Journal of Medicine 389, no. 18 (2023): 1672–1684.

[6] T. Cascone, M. M. Awad, J. D. Spicer, et al., “Perioperative Nivolumab in Resectable Lung Cancer,” New England Journal of Medicine 390, no. 19 (2024): 1756–1769.

[7] L. Zhang, J. Chen, T. Cheng, H. Yang, H. Li, and C. Pan, “Identification of the Key Genes and Characterizations of Tumor Immune Microenvironment in Lung Adenocarcinoma (LUAD) and Lung Squamous Cell Carcinoma (LUSC),” Journal of Cancer 11, no. 17 (2020): 4965–4979.

[8] W. Liang, K. Cai, C. Chen, et al., “Expert Consensus on Neoadjuvant Immunotherapy for Non-Small Cell Lung Cancer,” Translational Lung Cancer Research 9, no. 6 (2020): 2696–2715.

[9] R. Laza-Briviesca, A. Cruz-Bermúdez, E. Nadal, et al., “Blood Biomarkers Associated to Complete Pathological Response on NSCLC Patients Treated With Neoadjuvant Chemoimmunotherapy Included in NADIM Clinical Trial,” Clinical and Translational Medicine 11, no. 7 (2021): e491.

[10] M. Hu, X. Li, H. Lin, et al., “Easily Applicable Predictive Score for MPR Based on Parameters Before Neoadjuvant Chemoimmunotherapy in Operable NSCLC: A Single-Center, Ambispective, Observational Study,” International Journal of Surgery 110, no. 4 (2024): 2275–2287.

[11] E. Lo Presti, F. Dieli, and S. Meraviglia, “Tumor-Infiltrating γδ T Lymphocytes: Pathogenic Role, Clinical Significance, and Differential Programing in the Tumor Microenvironment,” Frontiers in Immunology 5 (2014): 607.

[12] C. Zhou, G. Chen, Y. Huang, et al., “Camrelizumab Plus Carboplatin and Pemetrexed Versus Chemotherapy Alone in Chemotherapy-Naive Patients With Advanced Non-Squamous Non-Small-Cell Lung Cancer (CameL): A Randomised, Open-Label, Multicentre, Phase 3 Trial,” Lancet Respiratory Medicine 9, no. 3 (2021): 305–314.

[13] S. Ren, J. Chen, X. Xu, et al., “Camrelizumab Plus Carboplatin and Paclitaxel as First-Line Treatment for Advanced Squamous NSCLC (CameL-Sq): A Phase 3 Trial,” Journal of Thoracic Oncology 17, no. 4 (2022): 544–557.

[14] D. Yue, W. Wang, H. Liu, et al., “Perioperative Tislelizumab Plus Neoadjuvant Chemotherapy for Patients With Resectable Non-Small-Cell Lung Cancer (RATIONALE-315): An Interim Analysis of a Randomised Clinical Trial,” Lancet Respiratory Medicine 13, no. 2 (2025): 119–129.

[15] F. Liang, G. Z. Wang, Y. Wang, et al., “Tobacco Carcinogen Induces Tryptophan Metabolism and Immune Suppression via Induction of Indoleamine 2,3-Dioxygenase 1,” Signal Transduction and Targeted Therapy 7, no. 1 (2022): 311.

[16] T. L. Ng, Y. Liu, A. Dimou, et al., “Predictive Value of Oncogenic Driver Subtype, Programmed Death-1 Ligand (PD-L1) Score, and Smoking Status on the Efficacy of PD-1/PD-L1 Inhibitors in Patients With Oncogene-Driven Non-Small Cell Lung Cancer,” Cancer 125, no. 7 (2019): 1038–1049.

[17] J. J. N. Li, K. Karim, M. Sung, et al., “Tobacco Exposure and Immunotherapy Response in PD-L1 Positive Lung Cancer Patients,” Lung Cancer 150 (2020): 159–163.

[18] Y. Wu, J. Ma, X. Yang, et al., “Neutrophil Profiling Illuminates Anti-Tumor Antigen-Presenting Potency,” Cell 187, no. 6 (2024): 1422–1439.e24.

[19] N. Meshulami, S. Tavolacci, D. de Miguel-Perez, C. Rolfo, P. C. Mack, and F. R. Hirsch, “Predictive Capability of PD-L1 Protein Expression for Patients With Advanced NSCLC: Any Differences Based on Histology?,” Clinical Lung Cancer 24, no. 5 (2023): 401–406.

[20] Y. Li, J. Wang, L. Wu, et al., “Diversity of Dominant Peripheral T Cell Receptor Clone and Soluble Immune Checkpoint Proteins Associated With Clinical Outcomes Following Immune Checkpoint Inhibitor Treatment in Advanced Cancers,” Frontiers in Immunology 12 (2021): 649343.

[21] J. Han, J. Duan, H. Bai, et al., “TCR Repertoire Diversity of Peripheral PD-1(+)CD8(+) T Cells Predicts Clinical Outcomes After Immunotherapy in Patients With Non-Small Cell Lung Cancer,” Cancer Immunology Research 8, no. 1 (2020): 146–154.

[22] O. Pich, F. Muiños, M. P. Lolkema, N. Steeghs, A. Gonzalez-Perez, and N. Lopez-Bigas, “The Mutational Footprints of Cancer Therapies,” Nature Genetics 51, no. 12 (2019): 1732–1740.

[23] J. Zhang, Z. Ji, J. X. Caushi, et al., “Compartmental Analysis of T-Cell Clonal Dynamics as a Function of Pathologic Response to Neoadjuvant PD-1 Blockade in Resectable Non-Small Cell Lung Cancer,” Clinical Cancer Research 26, no. 6 (2020): 1327–1337.

[24] X. Zhao, X. Pan, Y. Wang, and Y. Zhang, “Targeting Neoantigens for Cancer Immunotherapy,” Biomarker Research 9, no. 1 (2021): 61.

[25] E. A. Eisenhauer, P. Therasse, J. Bogaerts, et al., “New Response Evaluation Criteria in Solid Tumours: Revised RECIST Guideline (version 1.1),” European Journal of Cancer 45, no. 2 (2009): 228–247.

[26] W. D. Travis, S. Dacic, I. Wistuba, et al., “IASLC Multidisciplinary Recommendations for Pathologic Assessment of Lung Cancer Resection Specimens after Neoadjuvant Therapy,” Journal of Thoracic Oncology 15, no. 5 (2020): 709–740.

[27] D. A. Bolotin, S. Poslavsky, I. Mitrophanov, et al., “MiXCR: Software for Comprehensive Adaptive Immunity Profiling,” Nature Methods 12, no. 5 (2015): 380–381.

[28] M. P. Lefranc, V. Giudicelli, P. Duroux, et al., “IMGT®, the International ImMunoGeneTics Information System® 25 Years On,” Nucleic Acids Research 43 (2015): D413–D422.

[29] H. Yang and K. Wang, “Genomic Variant Annotation and Prioritization With ANNOVAR and wANNOVAR,” Nature Protocols 10, no. 10 (2015): 1556–1566.

[30] S. Malikic, A. W. McPherson, N. Donmez, and C. S. Sahinalp, “Clonality Inference in Multiple Tumor Samples Using Phylogeny,” Bioinformatics 31, no. 9 (2015): 1349–1356.

[31] J. Hundal, S. Kiwala, J. McMichael, et al., “pVACtools: A Computational Toolkit to Identify and Visualize Cancer Neoantigens,” Cancer Immunology Research 8, no. 3 (2020): 409–420.

[32] Z. Sztupinszki, M. Diossy, M. Krzystanek, et al., “Migrating the SNP Array-Based Homologous Recombination Deficiency Measures to Next Generation Sequencing Data of Breast Cancer,” NPJ Breast Cancer 4 (2018): 16.

[33] F. Favero, T. Joshi, A. M. Marquard, et al., “Sequenza: Allele-Specific Copy Number and Mutation Profiles From Tumor Sequencing Data,” Annals of Oncology 26, no. 1 (2015): 64–70.

[34] F. Pierini and T. L. Lenz, “Divergent Allele Advantage at Human MHC Genes: Signatures of Past and Ongoing Selection,” Molecular Biology and Evolution 35, no. 9 (2018): 2145–2158.

[35] J. E. Chaft, F. Oezkan, M. G. Kris, et al., “Neoadjuvant Atezolizumab for Resectable Non-Small Cell Lung Cancer: An Open-Label, Single-Arm Phase II Trial,” Nature Medicine 28, no. 10 (2022): 2155–2161.

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