Neoadjuvant hypofractionated radiotherapy plus tislelizumab with anlotinib followed by adjuvant tislelizumab with anlotinib in patients with resectable non-small cell lung cancer (NSCLC): Preliminary analysis of a phase II trial (NEO-PIONEER).

8063 Background: Although neoadjuvant immune checkpoint inhibitors (ICIs) combined with chemotherapy is the current standard of care for resectable NSCLC, the optimal combination strategy to improve efficacy with low toxicity remains to be explored. Preclinical and clinical studies have shown that anti-angiogenic therapy can enhance the efficacy of immunotherapy and sensitize radiotherapy through a variety of mechanisms. We designed a trial to test the activity of triple therapy of radiotherapy, angiogenesis inhibitors and ICIs for resectable NSCLC. Methods: This is a prospective, single-arm, phase II (NCT06379087) to explore the efficacy and safety of hypofractionated radiotherapy followed by sequential tislelizumab and anlotinib in the perioperative treatment of resectable NSCLC. A total of 20 eligible patients aged 18 years or older, with histologically confirmed stage II/IIIA resectable NSCLC, and without prior systemic anticancer treatment or known EGFR mutations, ALK rearrangements or ROS1 fusions are enrolled. The treatment regimen involved hypofractionated radiotherapy on d1-3 (24 Gy/3 fractions), followed by tislelizumab plus anlotinib within 1 week for 2 cycles after radiotherapy. Patients without disease progression after two cycles were followed by surgical resection within 4-6 weeks after the last dose of neoadjuvant treatment, and receive adjuvant treatment with tislelizumab plus anlotinib after surgery up to 1 year. The primary endpoint was pCR rate. And the secondary endpoint was MPR rate, 1-year EFS rate and the incidence of treatment-related AE. Results: Between May 1, 2024, and December 31, 2024, a total of 10 patients were enrolled. 6 (60%) of them had pathological stage IIIA. All patients enrolled have completed radiotherapy and 2 cycles of neoadjuvant treatment with tislelizumab plus anlotinib. 1 patient experienced disease progression following neoadjuvant and did not receive surgery. 7 patients have underwent surgery. While 2 patients were waiting surgery. Among the 7 patients who underwent surgery, 5 (71.4%) of 7 patients achieved pCR, all 7 patients demonstrated a MPR. In terms of safety, 1 patient experienced grade 3-4 treatment related adverse events, which was alanine aminotransferase and aspartate aminotransferase. There were no treatment-related deaths reported during the study period. Conclusions: Preoperative hypofractionated radiotherapy followed by immunotherapy and anti-angiogenesis therapy is tolerable, leads to a clinically significant pCR. Clinical trial information: NCT06379087 .