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 neoadjuvant 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 discontinuation. 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%; 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 operating characteristic analysis revealed a significant correlation between the maximum reduction of standard uptake values and pathologic response (R = 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.