1444P - Sintilimab with two cycles nab-paclitaxel / platinum as first line therapy for advanced squamous non-small-cell lung cancer: The final analysis and biomarker results

Background

PD-1 antibody combined with 4-6 cycles platinum-based chemotherapy has been the standard 1st line treatment for recurrent or advanced squamous (sq)-NSCLC. This study evaluated the effect and safety of sintilimab plus 2 cycles nab-paclitaxel/carboplatin for treatment-naïve stage IIIB-IV sq-NSCLC.

Methods

This is a single arm, multi-center, phase II study, advanced sq-NSCLC patients received sintilimab (200mg, IV) with nab-paclitaxel / carboplatin every 3 weeks for 2 cycles, followed by sintilimab (200mg, Q3W) until disease progression, or unacceptable toxic effects, or up to 2 years. The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), duration of response (DOR), overall survival (OS) and safety. Peripheral blood circulating tumor DNA (ctDNA) were measured at baseline as well after 1 cycle (C1) and 2 cycles (C2) treatment. Here we report the final analysis and biomarker results.

Results

48 patients were enrolled, 47 received at least once treatment, 44 had at least once tumor assessment. The median PFS and OS were 10.68 months (95%CI: 6.4-17.8) and 21.9 months (95% CI: 17.0-NE). PFS rates at 12m and 24m were 38.2% and 20.4%. OS rates at 12m and 24m were 78.9% and 47.8%. The ORR and DCR were 70.5% (95%CI: 54.8-83.2) and 93.2% (95%CI: 81.3-98.6), with a median DOR of 16.5m (95%CI: 7.0-20.6). 42 patients (91.3%) experienced treatment related adverse events (TRAEs), 5 were grade3/4, the most common TRAE were anemia, α-hydroxybutyrate dehydrogenase elevated and alanine aminotransferase elevated. Patients with abnormalities in BRAC2, BRINP2, FBXW7, KIT or RB1 exhibited a poorer PFS. The clearance of ctDNA after C2 treatment was found to be an independent predictor of superior response and longer PFS. Median PFS for patients with cleared ctDNA versus those with uncleared ctDNA were 18.1m compared to 4.3m, respectively.

Conclusions

Sintilimab combined with two cycles nab-paclitaxel/carboplatin showed encouraging PFS/OS and manageable safety as first line treatment for advanced squamous NSCLC. The ctDNA clearance might be a potential predictor for the efficacy.

Clinical trial identification

ChiCTR1900021726.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Innovent Biologics, Inc.

Disclosure

All authors have declared no conflicts of interest.