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

BackgroundNeoadjuvant immune checkpoint inhibitors (ICIs) combined with chemotherapy is the current standard of care in patients (pts) with resectable non-small cell lung cancer (NSCLC), followed by adjuvant platinum-based chemotherapy and subsequent therapy with ICIs. Despite improved efficacy with the addition of neoadjuvant immunotherapy to chemotherapy, the optimal combination strategy remains to be explored, especially for pts who cannot tolerate or refuse chemotherapy. Additionally, preclinical and clinical studies have shown that anti-angiogenic therapy can enhance the efficacy of immunotherapy and sensitize radiotherapy through a variety of mechanisms. However, it is unclear whether angiogenesis inhibitors can enhance the effect of radio-immunotherapy. A preclinical study suggests that anti-angiogentic therapy might be a potential synergistic modality for radio-immunotherapy in NSCLC pts. Therefore, triple therapy of radiotherapy, angiogenesis inhibitors and ICIs may be more effective in resectable NSCLC.Trial designThis is a prospective, single-arm, phase II, single-center trial (NCT06379087) to explore the efficacy and safety of hypofractionated radiotherapy sequential tislelizumab and anlotinib in the perioperative treatment of resectable NSCLC. Adult pts (n=20) with histologically confirmed, stage II/IIIA resectable NSCLC; without prior systemic anticancer treatment or known EGFR mutations, ALK rearrangements or ROS1 fusion are eligible. The enrolled pts first receive 24 Gy (8 Gy x 3 fractions) of hypofractionated treatment on d1-3, followed with tislelizumab plus anlotinib within 1 week for 2 cycles after radiotherapy. Pts will undergo radical surgery 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 1-year event-free survival rate. And the secondary endpoint was pathological complete response rate, major pathological response and the incidence of treatment-related adverse events.Clinical trial identificationNCT06379087.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.