Efficacy, Safety, and Biomarker Analysis of Neoadjuvant Camrelizumab and Apatinib in Patients With Resectable NSCLC: A Phase 2 Clinical Trial

Introduction: Camrelizumab (an anti-programmed cell death protein-1 antibody) combined with apatinib (an antiangiogenic agent) has conferred benefits for advanced NSCLC. We aimed to assess the activity and safety of neo-adjuvant camrelizumab plus apatinib in patients with resectable NSCLC.Methods: In this phase 2 trial, patients with histologically confirmed resectable stages IIA to IIIB NSCLC (stage IIIB, T3N2 only) received intravenous camrelizumab (200 mg) every 2 weeks for three cycles and oral apatinib (250 mg) once daily for 5 days followed by 2 days off for 6 weeks. Surgery was planned 3 to 4 weeks after apatinib discon-tinuation. The primary end point was major pathologic response (MPR) rate, assessed in patients who received at least one dose of neoadjuvant treatment and underwent surgery.Results: Between November 9, 2020, and February 16, 2022, 78 patients were treated and 65 (83%) underwent surgery. All 65 patients achieved an R0 surgical resection. Among the 65 patients, 37 (57%, 95% confidence interval [CI]: 44%-69%) had an MPR, of whom 15 (23%, 95% CI: 14%-35%) had a pathologic complete response (pCR). Pathologic responses observed in squamous cell NSCLC were superior to adenocarcinoma (MPR: 64% versus 25%; rate enrolled MPR, Four treatment treatment ating tion values addition, HOXA9 pCR: 28% versus 0%). The radiographic objective response rate was 52% (95% CI: 40%-65%). Among all the 78 enrolled patients, 37 (47%, 95% CI: 36%-59%) had an MPR, of whom 15 (19%, 95% CI: 11%-30%) had a pCR. Four (5%) of 78 patients had grade 3 neoadjuvant treatment-related adverse events. No grade 4 or 5 treatment-related adverse events occurred. Receiver oper-ating characteristic analysis revealed a significant correla-tion between the maximum reduction of standard uptake values and pathologic response (R 1/4 0.619, p < 0.0001). In addition, baseline programmed death-ligand 1 expression, HOXA9 and SEPT9 methylation levels, and circulating tumor DNA status before surgery were associated with pathologic responses.Conclusions: Neoadjuvant camrelizumab plus apatinib was found to have promising activity and manageable toxicity in patients with resectable stages IIA to IIIB NSCLC, which might be a potential therapeutic option in neoadjuvant setting.(c) 2023 Published by Elsevier Inc. on behalf of International Association for the Study of Lung Cancer.