Randomized multicenter phase II trial of radioimmunotherapy versus chemoimmunotherapy followed by surgery for c-stage IB-III NSCLC (RICHIS trial).

Abstract

TPS8132 Background: Chemotherapy combined with PD-1 or PD-L1 blockade (chemo-immunotherapy, ChemoIO), administered in the neoadjuvant, adjuvant, or perioperative setting, has become standard of care for surgically resectable non-small cell lung cancer (NSCLC). However, ChemoIO may be associated with significant toxicity that may limit treatment delivery and compromise surgical fitness. Preclinical data demonstrate that non-ablative stereotactic body radiotherapy (SBRT) can synergize with immunotherapy by enhancing tumor antigen release, interferon signaling, T-cell priming, and systemic antitumor immunity. We previously completed a phase II trial comparing neoadjuvant non-ablative SBRT (24 Gy) plus immunotherapy (SBRT-IO) versus immunotherapy alone, demonstrating favorable tolerability and higher rates of major and complete pathological response (MPR, pCR) in the SBRT-IO arm. SBRT-IO may therefore represent a neoadjuvant alternative for selected patients, with the potential to reduce treatment-related toxicity. Methods: RICHIS (NCT06623656) is an open-label, multicenter, randomized phase II trial enrolling approximately 112 patients with histologically confirmed, surgically resectable clinical stage IB-III (N2) NSCLC. Eligible patients are ≥18 years old, have ECOG performance status 0-1, and lack EGFR mutations or ALK fusions. Participants are randomized 1:1 to receive neoadjuvant SBRT-IO (SBRT 8 Gy × 3 fractions plus up to three cycles of cemiplimab) or standard ChemoIO (platinum-based doublet chemotherapy plus up to three cycles of cemiplimab). Randomization is stratified by tumor PD-L1 expression ( < 1% vs. ≥1%) and clinical stage (IB/II vs. III). Following neoadjuvant therapy, all patients undergo surgical resection and receive adjuvant cemiplimab for up to 12 months; patients in the SBRT-IO arm may additionally receive adjuvant chemotherapy. The primary endpoint is pCR. Key secondary endpoints include grade 3-5 adverse events (neoadjuvant and postoperative), event-free survival, MPR, and postoperative length of stay. Correlative immune and molecular biomarker studies are planned. Trial enrollment began on 2/4/2025 and is currently enrolling across 2 sites, with planned enrollment at 5 US sites. 19 of 112 patients are currently accrued. Clinical trial information: 24-02027124 .