Innovent Biologics, Inc...announced that the final analysis results of ORIENT-15, the Phase 3 study evaluating sintilimab in combination with chemotherapy for the first-line treatment of esophageal squamous cell carcinoma (ESCC)…Sintilimab plus chemotherapy significantly improved the median overall survival (mOS) over placebo plus chemotherapy with a 33.9% reduction in risk of death (HR 0.661; P<0.0001) and a 4.6-month improvement in mOS (17.4 vs 12.8 months) in all randomized patients (the ITT population); and 36.5% reduction in risk of death (HR 0.635; P=0.0001) and a 3.9-month improvement in mOS (18.4 vs 14.5 months) in PD-L1 positive patients (defined as combined positive score [CPS] ≥10).

Sintilimab and chemotherapy significantly improved progression free survival compared with placebo and chemotherapy in all patients (7.2 v 5.7 months, 0.56, 0.46 to 0.68, P<0.001) and in patients with combined positive scores of ≥10 (8.3 v 6.4 months, 0.58, 0.45 to 0.75, P<0.001)...Compared with placebo, sintilimab in combination with cisplatin plus paclitaxel showed significant benefits in overall survival and progression free survival as first line treatment in patients with advanced or metastatic oesophageal squamous cell carcinoma.

PFS was superior with S+C vs C in...CPS ≥10 pts (median 8.3 vs 6.4 mo, HR 0.580, 95% CI 0.449-0.749, P <0.0001)....ORR was 78.7 vs 57.5% in CPS ≥10 pts, with median DOR of 8.5 vs 5.5 mo....OS, PFS and ORR are all significantly improved in S+C vs C, with a manageable safety profile in the pts with PD-L1 CPS ≥10...The results demonstrate that the combination of sintilimab and chemo can be considered as a new 1L treatment in patients with advanced or metastatic ESCC.

Sintilimab + chemo vs chemo was superior for OS in all pts...and CPS ≥10 pts...PFS was superior with S+C vs C in all pts...and CPS ≥10 pts...ORR was 75.5 vs 56.9% in all pts, with median DOR of 8.3 vs 5.6 mo. ORR was 78.7 vs 57.5% in CPS ≥10 pts, with median DOR of 8.5 vs 5.5 mo....OS, PFS and ORR are all significantly improved in S+C vs C, with a manageable safety profile in the pts with PD-L1 CPS ≥10 and all pts.

PFS was superior with S+C vs C in...CPS ≥10 pts (median 8.3 vs 6.4 mo, HR 0.580, 95% CI 0.449-0.749, P <0.0001)....ORR was 78.7 vs 57.5% in CPS ≥10 pts, with median DOR of 8.5 vs 5.5 mo....OS, PFS and ORR are all significantly improved in S+C vs C, with a manageable safety profile in the pts with PD-L1 CPS ≥10...The results demonstrate that the combination of sintilimab and chemo can be considered as a new 1L treatment in patients with advanced or metastatic ESCC.

...Could provide archival or fresh tissues for PD-L1 expression analysis with obtainable results. ...

...For subjects who have received (neo)adjuvant or definitive chemotherapy/radiochemotherapy, time from the completion of last treatment to disease recurrence must be > 6 months Could provide archival or fresh tissues for PD-L1 expression analysis with obtainable results...

In this study, we sought to evaluate the efficacy and discover biomarkers and establish an artificial intelligence (AI) model to predict the efficacy of the combination of sintilimab and chemotherapy in the treatment of patients with ESCC....The mPFS of the PD-L1 positive population was significantly better than that of the PD-L1 negative population (19.23 months vs. 6.57 months, p = 0.046).

High tumor PD-L1 expression (TPS ≥1% or ≥10%) might indicate more response benefit to sintilimab for these pts, and low NLR might be a positive predictive factor for sintilimab.