The efficacy of PD-1 antibody sintilimab on ground glass opacity lesions in patients with early-stage multiple primary lung cancer (CCTC-1901, NCT04026841).

Abstract

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Background: Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) have been proven its significant efficacy on advanced non-small cell lung cancer (NSCLC). However, it remains unknown and is of great interest whether the PD-1 antibody affects early-stage lung cancer. Here, we reported the preliminary efficacy and safety outcomes of sintilimab on these early-stage GGO lesions in patients (pts) with multiple primary lung cancer in the CCTC-1901 study, the first trial evaluating PD-1 antibody in preinvasive or low invasive lung cancer worldwide. Methods: This single-center, phase II, Simon's two-stage design trial included pts who had a pathological diagnosis of resected lung cancer and at least one unresectable GGO lesion suspicious malignant which evaluated by a multidisciplinary team's consensus. The enrolled pts received 4 cycles of intravenous sintilimab 200 mg every 3 weeks. The primary endpoint is the objective response rate (ORR) of unresectable GGO lesions. For persistent GGO lesions that did not respond to treatment, either observation or second operation was taken. Also, immune biomarkers (T/B/NK subpopulation etc.) were monitored during treatment to validate the immune activity. Results: A total of 36 pts were included, with median age 59.5 (53.5-69), 66.7% females, 80.6% never smokers. All resected lesions were adenocarcinomas, of which 52.8% were EGFR mutated. 49 unresected GGOs (pure 11[22.4%], mixed 38[77.6%]) were defined as target lesions from 36 enrolled pts, with a mean size of 13.20±5.06 mm. The ORR (RECIST v1.1) was 5.6% (2/36, 1 PR and 1 CR); none of the pts had PD. Additionally, 3 non-target lesions (unresected solid lesions) from 3 included pts showed PR after the treatment of sintilimab, and the rest lesions (target or non-target) of 31 pts performed SD. Grade 1-2 fatigue (13, 36%), rash (13, 36%) and arthralgia (8, 22%) were the most common treatment-related adverse events (TrAEs), and no grade 3-5 TrAEs occurred. The proportion of CD8 ⁺ T-cell and the ratio of CD8 ⁺/CD4 ⁺ in 5 patients who showed PR of unresected lesions were significantly higher compared to those with SD lesions at baseline (CD8 ⁺ 36.6% vs 24.6%, p < 0.01; CD8 ⁺/CD4 ⁺ 1.09±0.18 vs 0.64±0.22, p < 0.01). Conclusions: This study is the first to confirm that PD-1 antibody sintilimab has immune-related antitumor activity on GGO-featured lung cancer and could be well tolerated among pts with early-stage lung cancer. Clinical trial information: NCT04026841.