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Phase 3 Completed N=512 Randomized Treatment

A Study of Tislelizumab (BGB-A317) Versus Chemotherapy as Second Line Treatment in Participants With Advanced Esophageal Squamous Cell Carcinoma

Source: ClinicalTrials.gov NCT03430843 ↗
Enrolled (actual)
512
Serious AEs
43.4%
Results posted
Dec 2023
Primary outcomePrimary: Overall Survival (OS) in the Intent-to-Treat (ITT) Analysis Set — 8.6; 6.3 Months — p=0.0001
◆ Published Evidence
Highly cited
306citations · ~77 / year
Tislelizumab Versus Chemotherapy as Second-Line Treatment for Advanced or Metastatic Esophageal Squamous Cell Carcinoma (RATIONALE-302): A Randomized Phase III Study.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022 · Open access · High-confidence link

Summary

The purpose of this study was to evaluate the efficacy and safety of tislelizumab as second line treatment in participants with advanced unresectable/metastatic ESCC that had progressed during or after first line therapy.

Linked Publications (5)

  • Tislelizumab Versus Chemotherapy as Second-Line Treatment for Advanced or Metastatic Esophageal Squamous Cell Carcinoma (RATIONALE-302): A Randomized Phase III Study.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022 · 306 citations · Open access · High-confidence link
  • <i>NOTCH1</i> 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.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025 · 15 citations · Open access · Likely link
  • Circulating tumor DNA serial monitoring of relapse and responses to tislelizumab immunotherapy as second‑line monotherapy for metastatic esophageal squamous cell carcinoma: A prospective study.
    Molecular and clinical oncology · 2024 · 4 citations · Open access · Likely link
  • Second-line tislelizumab versus chemotherapy in Japanese patients with advanced or metastatic esophageal squamous cell carcinoma: subgroup analysis from RATIONALE-302.
    Esophagus : official journal of the Japan Esophageal Society · 2024 · 1 citation · Open access · Likely link
  • Comparative Efficacy and Safety of Tislelizumab in Second-Line Esophageal Squamous Cell Carcinoma: Systematic Literature Review and Simulated Treatment Comparisons.
    Advances in therapy · 2026 · 0 citations · Open access · Likely link

Outcome Measures

OutcomeResultp-value
PRIMARY
Overall Survival (OS) in the Intent-to-Treat (ITT) Analysis Set
8.6; 6.3 0.0001 sig
SECONDARY
Overall Survival (OS) in the PDL-1 Positive Analysis Set
10.2; 5.1
SECONDARY
Objective Response Rate (ORR) in the ITT Analysis Set
20.3; 9.8
SECONDARY
Overall Response Rate (ORR) in the PD-L1 Positive Analysis Sets
26.3; 11.3
SECONDARY
Progression-free Survival (PFS) in the ITT Analysis Set
1.6; 2.1
SECONDARY
Progression-free Survival (PFS) in the PDL-1 Positive Analysis Set
2.7; 2.3
SECONDARY
Duration of Response (DOR) in the ITT Analysis Set
7.1; 4.0
SECONDARY
Duration of Response (DOR) in the PDL-1 Positive Analysis Set.
7.1; 5.7
SECONDARY
Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C-30) in the ITT Analysis Set
16.2; 18.3; 0.2; 4.8
SECONDARY
HRQoL as Assessed by EORTC QLQ-C30 in the PDL-1 Positive Analysis Set
16.8; 18.8; 0.5; 0.5
SECONDARY
HRQoL as Assessed by EORTC QLQ-Oesophagus Cancer Module (EORTC QLQ-OES18) Reported in ITT Analysis Set
14.7; 16.3; -0.6; 3.0
SECONDARY
HRQoL as Assessed by EORTC QLQ-OES18) in the PDL-1 Positive Analysis Set.
16.5; 18.1; -0.9; -2.9
SECONDARY
HRQoL as Assessed by European Quality of Life 5-Dimensions 5-Level Questionnaire (EQ-5D-5L) in the ITT Analysis Set
73.7; 72.5; -0.6; -5.9
SECONDARY
HRQoL as Assessed by EQ-5D-5L in the PD-L1 Positive Analysis Set
74.1; 70.5; -0.5; 4.4
SECONDARY
Number of Participants Experiencing Adverse Events (AEs)
245; 236; 109; 106

Eligibility Criteria

Key Inclusion Criteria

  • Histologically confirmed diagnosis of esophageal squamous cell carcinoma (ESCC)
  • Tumor progression during or after first-line treatment for advanced unresectable / metastatic ESCC
  • At least one measurable/evaluable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 prior to randomization

Key Exclusion Criteria

  • Receipt of 2 or more prior systemic treatments for advanced/metastatic unresectable ESCC
  • History of gastrointestinal perforation and /or fistula or aorto-esophageal fistula within 6 months prior to randomization
  • Tumor invasion into organs located adjacent to the esophageal disease site (eg, aorta or respiratory tract) at an increased risk of fistula in the study treatment assessed by investigator
  • Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage
  • Received prior therapies targeting programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1)
  • Prior malignancy active within the previous 2 years (exceptions include the tumor under investigation in this trial, and locally recurring cancers that have undergone curative treatment, such as resected basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the prostate, cervix or breast)
  • Active brain or leptomeningeal metastasis.
  • Has active autoimmune disease or history of autoimmune diseases at high risk for relapse
  • Known history of, or any evidence of interstitial lung disease, non-infectious pneumonitis, pulmonary fibrosis diagnosed based on imaging or clinical findings, or uncontrolled systemic diseases, including diabetes, hypertension, acute lung diseases, etc
  • Known history of Human Immunodeficiency Virus (HIV)
  • Has cardiovascular risk factors
  • Pregnant or breastfeeding woman.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03430843) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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