New Reference: NOTCH1 Mutation as a Predictive Marker for Tislelizumab

Randomized, open-label, phase 3 trial (RATIONALE-302)

Advanced or metastatic ESCC patients after progression on 1st-line treatment

Tislelizumab 200 mg every 3 wks vs. Investigator’s choice chemotherapy (paclitaxel, docetaxel, or irinotecan)

ORR in NOTCH1-mutant pts: 33% vs. 8% (tislelizumab vs. chemo)

ORR in NOTCH1-WT pts: 18% vs. 16%

mOS: 18.4 mos vs. 5.3 mos in NOTCH1-mutant pts (HR: 0.35 [0.17-0.71])

mOS in NOTCH1 WT pts: HR: 0.81 [0.57-1.14]

OS with NOTCH1 mutation in PD-L1 TAP ≥10% subgroup: HR: 0.31 [0.11-0.86]

OS in NOTCH1-mutant pts with TMB-high: HR: 0.34 [0.12-0.98]

OS in NOTCH1-mutant pts with TMB-low: HR: 0.38 [0.14-1.02]

Not reported separately in this biomarker analysis article

Lu Z,Du W,Jiao X NOTCH1 Mutation and Survival Analysis of Tislelizumab in Advanced or Metastatic Esophageal Squamous Cell Carcinoma: A Biomarker Analysis From the Randomized, Phase III, RATIONALE-302 Trial

Reviewed by Ulas D. Bayraktar, MD on Apr 22, 2025