1232P An exploratory study of a PD-1 inhibitor for high-risk multiple ground-glass nodules (mGGNs) in synchronous stage I non-small cell lung cancer patients

Abstract

Surgical resection is recommended for stage I NSCLC patients. However, there is a lack of standard therapies for synchronous mGGNs. This study aims to explore the feasibility of a PD-1 inhibitor (sintilimab) in high-risk residual mGGNs in post-surgery synchronous stage I NSCLC patients. This is a single arm phase I trial aiming to recruit 20 subjects. Eligible patients contained at least one high-risk residual mGGN (confirmed by MDT discussion) after surgical resection of stage I NSCLC. Patients received sintilimab (200mg i.v., Q3W) for 10 cycles starting 6 weeks post-surgery. Radiological evaluations were performed every 3 cycles during the treatment period and every 3 months during follow-up. Whether re-operation is needed depends on MDT evaluation. The primary endpoints were safety and overall response rate (ORR). The secondary endpoints included duration of response (DOR), major pathologic response (MPR) of re-operated GGNs, and one-year progression-free survival (PFS). At data cutoff (23 Jan 2020), 20 patients (9 males and 11 females) were enrolled. The pathological results revealed that all had lung adenocarcinoma. The median number of treatment cycles was 6 (range 3 to 10). All lesions were evaluated as stable disease by RECIST 1.1. Six patients underwent re-operation safely and 12 GGNs were resected. Pathology showed that 1 had no residual tumour cells, 4 had 20-35%, and 7 had over 80%. Whole-exome sequencing of 12 GGNs showed 6 harbouring EGFR mutations and 2 harbouring KRAS mutations. Interestingly, 3 out of 6 with EGFR-mut showed less residual tumour cells (23.3%, 30%, and 80%). The highest TMB (15.7 mut/Mb) was observed in the complete response GGN. 65% patients experienced treatment-related 1-2 grade AEs. The PD-1 inhibitor was well tolerated and a certain degree of anti-tumour activity was seen from the pathologic results of re-operated GGNs. Radiological evaluation using RECIST 1.1 might be unsuitable for mGGNs. Further studies are needed to demonstrate the clinical benefits. ChiCTR: 1900022159.