Single-arm trial of neoadjuvant ipilimumab plus nivolumab with chemoradiotherapy in patients with resectable and borderline resectable lung cancer: the INCREASE study
Idris Bahce, Chris Dickhoff, Famke L. Schneiders, Joris D. Veltman, David J. Heineman, Sayed M.S. Hashemi, Anne Vrijmoet, Ilias Houda, Ezgi B Ulas, Joyce Bakker, Peter M. van de Ven, N. Bouwhuis, Lilian J. Meijboom, Daniela E. Oprea‐Lager, Febe van Maldegem, Marieke F. Fransen, Tanja D. de Gruijl, Teodora Radonic, Suresh Senan
Abstract
Background In non-small cell lung cancer (NSCLC), chemoradiotherapy (CRT) yields pathological complete response (pCR) rates of approximately 30%. We investigated using ipilimumab plus nivolumab (IPI-NIVO) with neoadjuvant CRT in resectable, and borderline resectable NSCLC. Methods This single-arm, phase-II trial enrolled operable T3-4N0–2 patients with NSCLC without oncogenic drivers. Primary study endpoints were safety, major pathological response (MPR) and pCR. Treatment encompassed platinum-doublet concurrent CRT, IPI 1 mg/kg intravenous and NIVO 360 mg intravenous on day-1, followed by chemotherapy plus NIVO 360 mg 3 weeks later. Thoracic radiotherapy was 50 or 60 Gy, in once-daily doses of 2 Gy. Resections were 6 weeks post-radiotherapy. Results In a total of 30 patients in the intention-to-treat (ITT) population, grades 3–4 treatment-related adverse events (TRAEs) occurred in 70%, one TRAE grade 5 late-onset pneumonitis on day 96 post-surgery (1/30, 3.3%) occurred, and one non-TRAE COVID-19 death (1/30, 3.3%). pCR and MPR were achieved in 50% (15/30) and 63% (19/30) of the ITT; and in 58% (15/26) and 73% (19/26) of the 26 patients who underwent surgery, respectively. Postoperative melanoma was seen in one non-pCR patient. The R0 rate was 100% (26/26), and no patient failed surgery due to TRAEs. In peripheral blood, proliferative CD8 + T cells were increased, while proliferative regulatory T cells (Tregs) were not. On-treatment, pCR-positives had higher CD8 + CD39 + T cells and lower HLA-DR + Tregs. Conclusions Neoadjuvant IPI-NIVO-CRT in T3-4N0–2 NSCLC showed acceptable safety with pCR and MPR in 58% and 73% of operated patients, respectively. No patient failed surgery due to TRAEs. Trial registration number NCT04245514 .