The preliminary results of a randomized phase II trial evaluating induction toripalimab plus chemotherapy followed by concurrent chemoradiotherapy and consolidation toripalimab in bulky unresectable stage III non-small-cell lung cancer (InTRist).

8012 Background: Unresectable stage III NSCLC patients with large tumor volumes remain challenging. Our previous retrospective study has showed promising results of induction chemoimmunotherapy before definitive chemoradiotherapy (CRT) for these patients. Here we report preliminary results of the randomized phase II study on this regimen. Methods: This InTRist study is a randomized, single-center, phase 2 trial, enrolling patients with unresectable stage III NSCLC with bulky diseases, and without EGFR/ALK alterations. Bulky diseases were defined as primary tumor ≥5 cm in greatest dimension or metastatic lymph nodes ≥2 cm in shortest diameter. Eligible patients were 1:1 randomly assigned to receive induction toripalimab (240 mg every 3 weeks) plus platinum-based doublet chemotherapy for 2 cycles (toripalimab group) versus induction chemotherapy alone for 2 cycles (chemo group) followed by concurrent CRT (60 Gy radiotherapy plus concurrent platinum-based chemotherapy). All patients without disease progression or grade ≥2 pneumonitis after CRT received consolidation toripalimab (240 mg every 3 weeks) for up to 12 months. Randomization was stratified according to histologic type. The primary endpoint was progression-free survival (PFS) from randomization. This trial is registered with ClinicalTrials.gov, NCT05888402. Results: BetweenJanuary 20th, 2023 and October 8th, 2024, 52 patients were randomized to induction toripalimab (n = 27) or chemo (n = 25) groups. By the data cutoff date (January 15th, 2025), the median follow-up was 13.1 months. Induction toripalimab plus chemotherapy exhibited significantly longer PFS compared to chemotherapy alone (median not reached [NR] vs NR; hazard ratio 0.25 [95% CI, 0.07-0.90], P =0.034). The 12-month PFS rate was 89.4% (95% CI, 76.0%-100%) in the toripalimab group and 57.8% (95% CI, 40.7%-81.9%) in the chemo group. Objective response rate after induction therapy was 77.8% (21/27) for the toripalimab group and 40.0% (10/25) for the chemo group (median tumor reduction 32% vs 21%). Grade 2 pneumonitis occurred in 26.9% (14/52) of all patients, with 18.5% (5/27) in the toripalimab group and 36.0% (9/25) in the chemo group. Grade 3 pneumonitis occurred in 7.7% (4/52) of all patients, with 11.1% (3/27) in the toripalimab group compared to 4.0% (1/25) in the chemo group. No grade 4-5 pneumonitis. Conclusions: Induction toripalimab plus chemotherapy, followed by concurrent CRT and consolidation toripalimab, demonstrated potentially improved short-term efficacy and manageable toxicity for patients with bulky unresectable stage III NSCLC. Further follow-up is necessary to confirm these results. Clinical trial information: NCT05888402 .