Approximately 40% of patients (pts) with esophageal cancer are diagnosed with advanced unresectable or metastatic disease; the 5-year survival rate for advanced disease is < 5%. Inhibition of PD-1 has demonstrated antitumor activity and was generally well tolerated in pts with advanced unresectable or metastatic ESCC. Tislelizumab, a humanized IgG4 monoclonal antibody, has high affinity and specificity for PD-1. Tislelizumab was specifically engineered to minimize FcϒR binding on macrophages that, based on preclinical evidence, is believed to minimize potentially negative interactions with other immune cells. A first-in-human study (NCT02407990) demonstrated that single-agent tislelizumab was generally well tolerated and had preliminary antitumor effects in pts with solid tumors, including ESCC. A recommended phase 3 dose of 200 mg administered IV every 3 weeks (Q3W) has been established for tislelizumab.
This phase 3, randomized study (NCT03430843) was designed to evaluate the efficacy, safety, and tolerability of tislelizumab compared with chemotherapy for second-line treatment of advanced unresectable/metastatic ESCC. Adult pts, aged ≥18 years, with histologically or cytologically confirmed ESCC that has progressed with first-line therapy, have ≥1 measurable/evaluable lesion, and have an Eastern Cooperative Oncology score ≤1 will be enrolled. Approximately 450 pts will be randomized (1:1) to receive either tislelizumab 200 mg IV Q3W or investigator-chosen chemotherapy (paclitaxel 135–175 mg/m2 IV Q3W or 100 mg/m2 IV weekly for 6 weeks with 1 week of rest [Japan only], docetaxel 75 mg/m2 or 70 mg/m2 IV Q3W, or irinotecan 125 mg/m2 IV Q3W). Overall survival is the primary endpoint; secondary endpoints include objective response rate, progression free survival, duration of response, and health-related quality-of-life outcomes. Safety/tolerability will be assessed by monitoring adverse events (AEs), including immune-related AEs, as well as physical examinations, vital signs, and electrocardiograms. As of 11 April 2018, 6 patients have been enrolled.
Clinical trial identification
Legal entity responsible for the study
Medical writing and editorial assistance was provided by Regina Switzer, PhD (SuccinctChoice Medical Communications, Chicago, IL).
J.A. Ajani: Honoraria, research funding: BWS, Five Prime Therapeutics, Medscape, Celgene, Taiho Pharmaceutical, Merck, Delta-Fly, Gilead. E. Van Cutsem: Consulting role, research funding: Baxter, Lilly, Roche, Servier, Amgen, Bayer, Boehringer, Celgene, MSO, Merck, Novartis, Ipsen, Roche, Sanofi. B. Guo: Employee, ownership interest: BeiGene. J. Song, V. Paton: Employee: BeiGene. K. Kato: Consulting role, speakers' bureau, research funding: Beigene, MSD, Ono Pharmaceutical, BMS, Eli Lilly, Shionogi, Merck Serono. All other authors have declared no conflicts of interest.