Phase IA/IB study of single-agent tislelizumab, an investigational anti-PD-1 antibody, in solid tumors

J Immunother Cancer. 2020 Jun;8(1):e000453. doi: 10.1136/jitc-2019-000453.


Background: The programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) axis plays a central role in suppressing antitumor immunity; axis dysregulation can be used by cancer cells to evade the immune system. Tislelizumab, an investigational monoclonal antibody with high affinity and binding specificity for PD-1, was engineered to minimize binding to FcγR on macrophages to limit antibody-dependent phagocytosis, a potential mechanism of resistance to anti-PD-1 therapy. The aim of this phase IA/IB study was to investigate the safety/tolerability, antitumor effects and optimal dose and schedule of tislelizumab in patients with advanced solid tumors.

Methods: Patients (aged ≥18 years) enrolled in phase IA received intravenous tislelizumab 0.5, 2, 5 or 10 mg/kg every 2 weeks; 2 or 5 mg/kg administered every 2 weeks or every 3 weeks; or 200 mg every 3 weeks; patients in phase IB received 5 mg/kg every 3 weeks. Primary objectives were to assess tislelizumab's safety/tolerability profile by adverse event (AE) monitoring and antitumor activity using RECIST V.1.1. PD-L1 expression was assessed retrospectively with the VENTANA PD-L1 (SP263) Assay.

Results: Between May 2015 and October 2017, 451 patients (n=116, IA; n=335, IB) were enrolled. Fatigue (28%), nausea (25%) and decreased appetite (20%) were the most commonly reported AEs. Most AEs were grade 1-2 severity; anemia (4.9%) was the most common grade 3-4 AE. Treatment-related AEs led to discontinuation in 5.3% of patients. Grade 5 AEs were reported in 14 patients; 2 were considered related to tislelizumab. Pneumonitis (2%) and colitis (1%) were the most common serious tislelizumab-related AEs. As of May 2019, 18% of patients achieved a confirmed objective response in phase IA and 12% in phase IB; median follow-up duration was 13.6 and 7.6 months, respectively. Pharmacokinetics, safety and antitumor activity obtained from both phase IA and IB determined the tislelizumab recommended dose; ultimately, tislelizumab 200 mg intravenous every 3 weeks was the dose and schedule recommended to be taken into subsequent clinical trials.

Conclusions: Tislelizumab monotherapy demonstrated an acceptable safety/tolerability profile. Durable responses were observed in heavily pretreated patients with advanced solid tumors, supporting the evaluation of tislelizumab 200 mg every 3 weeks, as monotherapy and in combination therapy, for the treatment of solid tumors and hematological malignancies.

Trial registration number: NCT02407990.

Keywords: immunotherapy; oncology; programmed cell death 1 receptor; tumors.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / pharmacokinetics
  • Antibodies, Monoclonal, Humanized / toxicity*
  • Area Under Curve
  • Colitis / chemically induced
  • Colitis / epidemiology
  • Colitis / immunology
  • Dose-Response Relationship, Drug
  • Drugs, Investigational / administration & dosage
  • Drugs, Investigational / pharmacokinetics
  • Drugs, Investigational / toxicity*
  • Female
  • Follow-Up Studies
  • Half-Life
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage
  • Immune Checkpoint Inhibitors / pharmacokinetics
  • Immune Checkpoint Inhibitors / toxicity*
  • Infusions, Intravenous
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Staging
  • Neoplasms / diagnosis
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Pneumonia / chemically induced
  • Pneumonia / epidemiology
  • Pneumonia / immunology
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / immunology
  • Response Evaluation Criteria in Solid Tumors
  • Retrospective Studies
  • Young Adult


  • Antibodies, Monoclonal, Humanized
  • Drugs, Investigational
  • Immune Checkpoint Inhibitors
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • tislelizumab

Associated data