P19.02 Sintilimab Plus Docetaxel in Previously Treated Advanced NSCLC, Updates on Progression-Free and Overall Survival

Abstract

Background: Our phase single-arm phase 2 study previously showed favorable efficacy of sintilimab plus docetaxel as second line therapy for advanced Chinese NSCLC patients. Here we presented the updated survival and safety data. Eligible patients were standard platinum doublet failure advanced NSCLC patients, who had not received any ICIs before. EGFR/ALK positive patients must be TKIs failure or intolerable. Participants would receive docetaxel (75mg/m2, day 1) plus sintilimab (200mg, day 3) every 3 weeks for 4-6 cycles followed by sintilimab maintenance until disease progression, unacceptable toxicity, or up to 2 years. The primary end point is progression-free survival (PFS) per RECIST v1.1. Secondary end points included overall response rate (ORR), duration of response (DOR), overall survival (OS), and safety. From 10/2019 to 11/2020, 40 patients were enrolled. Most were male (77.5%) and adenocarcinoma (87.5%). 25% (10/40) patients and 12.5% (5/40) had brain and liver metastasis at baseline, separately. Median follow-up was 9.0 months (range 1.6-16.2) as of data cut-off (2/19/2021). 13 patients temporarily suspended study treatment due to COVID-19, while 11 patients resumed treatment after documented progression-free. Among all, 9 patients were still on study treatment until data cut-off. Median PFS was 5.78 months (95%CI 4.3-8.28), and PFS rates at 6 months and 12 months were 47% and 23%. Median OS was 12.45 months (95%CI 5.82-12.62). 12 months OS rates was 64%. Of the 37 evaluable patients, ORR is 32.43% (95%CI 18.01%, 49.79%), DCR is 89.19% (95%CI 74.58%, 96.97%). Median DOR was 6.46 months (95% 1.28, NA). Median TTR (Time to Response) was 3.89 months (95% 1.61, 4.99). Efficacy of key subgroups are presented in Table 1.Table 1Selected subgroup analysis of Sintilimab Plus Docetaxel efficacy in Treated NSCLCSubgroupCategoryNORR%(95%CI)mPFS months(95%CI)Histological typeAdenocarcinoma3533.33(17.96,51.83)5.78(4.14,8.28)Squamous cell carcinoma525(0.63,80.59)8.46(2.3,NA)Smoking statusYES2230(11.89,54.28)5.72(3.02,6.51)NO1835.29(14.21,61.67)8.28(4.14,9.36)Brain/meningeal metastasisNO3031.03(15.28,50.83)5.78(3.55,8.77)YES1037.5(8.52,75.51)6.51(1.58,NA)Driver gene mutationKRAS +625(0.63,80.59)6.51(2.96,NA)EGFR-and TP53+1937.5(15.2,64.57)5.78(3.55,9.36)Best overall response of first-line treatmentPR640(5.27,85.34)5.22(2.3,NA)SD1341.67(15.17,72.33)8.77(4.3,NA)PD1145.45(16.75,76.62)8.28(1.58,NA)First-line treatment (EGFR wild type)Chemotherapy2436.36(17.2,59.34)8.28(4.3,12.62)Chemotherapy +Bevacizumab1236.36(10.93,69.21)5.72(1.77,6.01)Best overall response of study treatmentPR11-NA(5.52,NA)SD21-4.86(3.55,6.01)Maximum change of target lesions from baseline≤ 20%19-8.77(5.78,NA)≤0%29-8.28(5.52,12.62)>0%8-2.37(1.02,NA) Open table in a new tab Median treatment duration was 4.4 months (range 0.1-13.9). Overall, 72.5% (29/40) patients had experienced treatment-related adverse events (TRAEs), including 15% (6/40) grade ≥3 TRAEs. No AEs led to treatment discontinuation or death. The most common TRAEs were leukopenia (32.5%), neutropenia (17.5%), alopecia (12.5%), lymphopenia (7.5%), fatigue (7.5%) and diarrhea (7.5%). 27.5% (11/40) patients experienced potential immune related AEs (irAEs), including 1 grade 3 gamma-glutamyltransferase increase, 1 grade 2 hypothyroidism and 3 grade 2 pneumonitis. This is the first study of a PD-1 inhibitor plus chemotherapy in advanced Chinese NSCLC patients who had failed first-line standard therapy. The encouraging efficacy and tolerable safety profile suggest a potential role of this combination in second-line setting. Clinical trial information: ChiCTR1900027634.