Anti-PD-1 Monoclonal Antibody Tislelizumab (BGB-A317) Combined With or Without Anti-TIGIT Monoclonal Antibody Ociperlimab (BGB-A1217) in Participants With Recurrent or Metastatic Esophageal Squamous Cell Carcinoma (AdvanTIG-203)

A Phase 2, Multicenter, Randomized, Placebo-Controlled Study to Compare the Efficacy of Anti-PD-1 Monoclonal Antibody Tislelizumab (BGB-A317) Plus Anti-TIGIT Monoclonal Antibody Ociperlimab (BGB-A1217) Versus Tislelizumab Plus Placebo as Second-Line Treatment in Patients With PD-L1 Tumor Area Positivity (TAP) ≥ 10% Unresectable, Locally Advanced, Recurrent or Metastatic Esophageal Squamous Cell Carcinoma

A study of tislelizumab (BGB-A317) plus ociperlimab versus tislelizumab plus placebo as second-line treatment in participants with programmed cell death protein-ligand 1 (PD-L1) tumor area positivity (TAP) ≥ 10% unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma.

Study Overview

• Status: Completed
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Placebo; Biological: Tislelizumab; Biological: Ociperlimab

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Beijing Cancer hospital
  • Beijing, China
    • Beijing Friendship Hospital, Capital Medical University
  • Changzhi, China, 046000
    • Heping Hospital Affiliated to Changzhi Medical College
  • Changzhou, China
    • The First People's Hospital of Changzhou
  • Fujian, China
    • The First Affiliated Hospital of Fujian Medical University
  • Fujian, China
    • Fujian Cancer Hospital
  • Fujian, China
    • Zhongshan Hospital Xiamen University
  • Guangdong, China
    • Sun Yat-sen University Cancer Center
  • Guangdong, China
    • Nanfang Hospital of Southern Medical University
  • Guangdong, China
    • Cancer Hospital of Shantou University Medical College
  • Guangdong, China
    • The First Affiliated Hospital of Guangzhou University of Chinese Medicine
  • Guangdong, China
    • The Sixth Affiliated Hospital, Sun Yat-sen University
  • Guangxi, China
    • Guangxi Medical University Affiliated Tumor Hospital
  • Hainan, China
    • Hainan General Hospital
  • Hebei, China
    • Affiliated Hospital of Hebei University
  • Hefei, China
    • The Second Hospital of Anhui Medical University
  • Heilongjiang, China
    • Harbin Medical University Cancer Hospital
  • Henan, China
    • Henan Cancer Hospital
  • Henan, China
    • The First Affiliated Hospital of Xinxiang Medical University
  • Henan, China
    • The First Affiliated Hospital of Zhengzhou University
  • Hubei, China
    • Hubei Cancer Hospital
  • Hubei, China
    • Xiangyang Central Hospital
  • Hunan, China
    • Hunan Cancer Hospital
  • Jiangxi, China
    • The Second Affiliated Hospital of Nanchang University
  • Jiangxi, China
    • The First Affiliated Hospital of Nanchang University
  • Shandong, China
    • Linyi Cancer Hospital
  • Shandong, China
    • Weifang People's Hospital
  • Shanghai, China
    • Shanghai Chest Hospital
  • Shenyang, China
    • Liaoning cancer Hospital & Institute
  • Sichuan, China
    • Sichuan Provincial People's Hospital
  • Xuzhou, China
    • The Affiliated Hospital of Xuzhou Medical University
  • Yangzhou, China
    • Northern Jiangsu People's Hospital
  • Zhejiang, China
    • Hwa Mei Hospital, University of Chinese Academy of Sciences
  • Zhejiang, China
    • Hangzhou Cancer Hospital
  • Anhui
    • Hefei, Anhui, China, 230088
      • Anhui Provincial Cancer Hospital
  • Fujian
    • Quanzhou, Fujian, China, 362002
      • Quanzhou First Hospital of Fujian Province
    • Xiamen, Fujian, China, 361003
      • First Affiliated Hospital of Xiamen University
  • Gansu
    • Gansu, Gansu, China
      • Lanzhou University Second Hospital
  • Guangdong
    • Guangzhou, Guangdong, China
      • Guangdong Provincial Hospital of Chinese Medicine
    • Guangzhou, Guangdong, China
      • Meizhou Hospital Affiliated to Sun Yat-sen University
  • Hainan
    • Sanya, Hainan, China
      • Hainan Third People's Hospital
  • Jiangsu
    • Nantong, Jiangsu, China, 226000
      • Nantong Tumor Hospital
    • Wuxi, Jiangsu, China
      • Affiliated Hospital of Jiangnan University
  • Ningxia
    • Yinchuan, Ningxia, China
      • General Hospital of Ningxia Medical University
  • Qinghai
    • Qinghai, Qinghai, China
      • Qinghai Provincial People's Hospital
  • Shandong
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital
  • Shanxi
    • Taiyuan, Shanxi, China, 140100
      • Shanxi Provincial People's Hospital
  • Sichuan
    • Deyang, Sichuan, China
      • People's Hospital of Deyang City
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Medical University Cancer Institute & Hospital
  • Xinjiang
    • Ürümqi, Xinjiang, China
      • The First Affiliated Hospital of Xinjiang Medical University
  • Yunnan
    • Kunming, Yunnan, China
      • Yunnan Cancer Hospital
    • Yunnan, Yunnan, China
      • First Affiliated Hospital of Kunming Medical University
• France
  • Marseille, France
    • Hopital De La Timone
  • Paris, France, 75015
    • Hopital Europeen Georges Pompidou - Digestive Oncology
  • Poitiers, France, 80621
    • CHU de Poitiers
  • Picardie
    • Amiens Cedex 1, Picardie, France
      • Centre Hospitalier Universitaire d'Amiens - Hopital Sud
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of
    • Ajou University Hospital
  • Jeongnam, Korea, Republic of
    • Chonnam National University Hwasun Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of
    • The Catholic University of Korea, Seoul St. Mary's Hospital
• Spain
  • Barcelona, Spain
    • Hospital Clinic De Barcelona
  • Barcelona, Spain
    • Hospital De La Santa Creu I Sant Pau
  • Barcelona, Spain
    • Hospital Universitario Vall d'Hebron
  • L'Hospitalet De Llobregat, Spain
    • Institut Catala d'Oncologia
  • Madrid, Spain
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain
    • Hospital Universitario Madrid Sanchinarro
  • Málaga, Spain
    • Hospital Regional Universitario de Málaga
  • Santander, Spain
    • Hospital Universitario Marques de Valdecilla
  • Valencia, Spain
    • Hospital Clinico Universitario de Valencia - INCLIVA
  • Zaragoza, Spain
    • Hospital Universitario Miguel Servet
• Taiwan
  • Chiayi City, Taiwan
    • Chiayi Chang Gung Memorial Hospital
  • Kaohsiung, Taiwan
    • Kaohsiung Chang Gung Memorial Hospital
  • Taichung, Taiwan
    • China Medical University Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Taipei Veterans General Hospital
  • Taoyuan, Taiwan
    • Linkou Chang Gung Memorial Hospital
• Thailand
  • Bangkok, Thailand
    • Siriraj Hospital
  • Bangkok, Thailand
    • Rajavithi Hospital
  • Bangkok, Thailand
    • Phramongkutklao Hospital
  • Bangkok, Thailand
    • Chulabhorn Hospital
  • Chiang Mai, Thailand
    • Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University
  • Hat Yai, Thailand
    • Songklanagarind Hospital, Prince of Songkla University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Histologically confirmed diagnosis of esophageal squamous cell carcinoma (ESCC).
2. Have progressive disease during or after first-line of systemic treatment for unresectable, locally advanced, recurrent or metastatic ESCC.
3. Have measurable disease as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
4. Have confirmed programmed cell death protein-ligand 1 (PD-L1) tumor area positivity (TAP) ≥ 10% in tumor tissues tested by the central lab.
5. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.

Key Exclusion Criteria:

1. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains, or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways.
2. Participants with evidence of fistula (either esophageal/bronchial or esophageal/aorta).
3. Evidence of complete esophageal obstruction not amenable to treatment.
4. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage (recurrence within 2 weeks after intervention).
5. Has received any chemotherapy, immunotherapy (eg, interleukin, interferon, thymosin, etc) or any investigational therapies within 14 days or 5 half-lives (whichever is longer) before the first dose of study drug. Or has received palliative radiation treatment or other local regional therapies within 14 days before the first dose of study drug.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Tislelizumab plus Ociperlimab; Participants received 200 milligrams (mg) tislelizumab plus 900 mg ociperlimab intravenously once every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of informed consent, whichever occurred first.	Biological: Tislelizumab; Tislelizumab is a monoclonal antibody formulated for intravenous injection.; Other Names: BGB-A317; TEVIMBRA®; Biological: Ociperlimab; Ociperlimab is a monoclonal antibody formulated for intravenous injection.; Other Names: BGB-A1217
Placebo Comparator: Arm B: Tislelizumab plus Placebo; Participants received 200 mg tislelizumab plus placebo intravenously once every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of informed consent, whichever occurred first.	Drug: Placebo; Ociperlimab placebo injection is a sterile, preservative-free solution for infusion formulated in the same buffer as ociperlimab active drug.; Other Names: Ociperlimab placebo; Biological: Tislelizumab; Tislelizumab is a monoclonal antibody formulated for intravenous injection.; Other Names: BGB-A317; TEVIMBRA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Assessed by the Investigator	Objective response rate is defined as the percentage of participants who had a best overall response of confirmed complete response (CR) or partial response (PR) assessed by the Investigator according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Response evaluations were performed using computed tomography or magnetic resonance imaging (MRI) approximately every 6 weeks for the first 54 weeks and then every 12 weeks thereafter. CR: Disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or non-target) < 10 mm, and no new lesions. PR: At least a 30% decrease in the size of target lesions, with no progression of non-target lesions and no new lesions, or disappearance of target lesions with persistence of 1 or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, and no new lesions. Response (CR or PR) must have been confirmed 4 weeks or later after the first response was observed.	Up to the primary analysis data cutoff date of 01 February 2023; median (range) time on follow-up was 7.4 (0.5 - 20.1) months in Arm A and 6.4 (0.4 - 20.2) months in Arm B.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival (OS) is defined as the time from the date of randomization until the date of death due to any cause. Median overall survival was estimated using the Kaplan-Meier method. For participants who were still alive at the end of the trial, OS was censored at the last known alive date or the date of data cutoff, whichever was earlier.	From randomization to the end of the study, median (range) time on follow-up was 10.0 (0.5 - 29.9) months in Arm A and 7.8 (0.4 - 29.3) months in Arm B.
Objective Response Rate Assessed by the Independent Review Committee	Objective response rate is defined as the percentage of participants who had a best overall response of confirmed complete response (CR) or partial response (PR) assessed by the Independent Review Committee (IRC) according to RECIST v1.1. Response evaluations were performed using computed tomography or MRI approximately every 6 weeks for the first 54 weeks and then every 12 weeks thereafter. CR: Disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or non-target) < 10 mm, and no new lesions. PR: At least a 30% decrease in the size of target lesions, with no progression of non-target lesions and no new lesions, or disappearance of target lesions with persistence of 1 or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, and no new lesions. Response (CR or PR) must have been confirmed 4 weeks or later after the first response was observed.	Up to the primary analysis data cutoff date of 01 February 2023; median (range) time on follow-up was 7.4 (0.5 - 20.1) months in Arm A and 6.4 (0.4 - 20.2) months in Arm B.
Progression-free Survival (PFS) Assessed by the Independent Review Committee	Progression-free survival is defined as the time from the date of randomization to the date of first documentation of progressive disease assessed by the Independent Review Committee per RECIST v1.1, or death, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Progressive Disease (PD): At least a 20% increase in the size of target lesions with an absolute increase of at least 5 mm, or unequivocal progression of existing non-target lesions, or the appearance of any new lesions.	From randomization up to the primary analysis data cutoff date of 01 February 2023; median (range) time on follow-up was 7.4 (0.5 - 20.1) months in Arm A and 6.4 (0.4 - 20.2) months in Arm B.
Progression-free Survival (PFS) Assessed by the Investigator	Progression-free survival is defined as the time from the date of randomization to the date of first documentation of progressive disease assessed by the Investigator per RECIST v1.1, or death, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Progressive Disease (PD): At least a 20% increase in the size of target lesions with an absolute increase of at least 5 mm, or unequivocal progression of existing non-target lesions, or the appearance of any new lesions.	From randomization to the end of the study, median (range) time on follow-up was 10.0 (0.5 - 29.9) months in Arm A and 7.8 (0.4 - 29.3) months in Arm B.
Duration Of Response (DOR) Assessed by the Independent Review Committee	Duration of response is defined as the time from the first determination of an objective response (CR or PR) until the first documentation of progressive disease as assessed by the Independent Review Committee per RECIST v1.1, or death, whichever occurred first. Median DOR was estimated using the Kaplan-Meier method.	From randomization up to the primary analysis data cutoff date of 01 February 2023; median (range) time on follow-up was 7.4 (0.5 - 20.1) months in Arm A and 6.4 (0.4 - 20.2) months in Arm B.
Duration Of Response (DOR) Assessed by the Investigator	Duration of response is defined as the time from the first determination of an objective response (CR or PR) until the first documentation of progressive disease as assessed by the Investigator per RECIST v1.1, or death, whichever occurred first. Median DOR was estimated using the Kaplan-Meier method.	From randomization to the end of the study, median (range) time on follow-up was 10.0 (0.5 - 29.9) months in Arm A and 7.8 (0.4 - 29.3) months in Arm B.
Disease Control Rate Assessed by the IRC And the Investigator	Disease Control Rate is defined as the percentage of participants who had confirmed CR, PR, or stable disease (SD) assessed by the IRC and the investigator per RECIST v1.1. Response evaluations were performed using computed tomography or MRI approximately every 6 weeks for the first 54 weeks and then every 12 weeks thereafter. CR: Disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or non-target) < 10 mm, and no new lesions. PR: At least a 30% decrease in the size of target lesions, with no progression of non-target lesions and no new lesions, or disappearance of target lesions with persistence of 1 or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, and no new lesions. SD: Neither sufficient shrinkage in size of lesions to qualify for PR nor sufficient increase to qualify for PD, and no new lesions. Response (CR or PR) must have been confirmed 4 weeks or later after the first response.	Up to the primary analysis data cutoff date of 01 February 2023; median (range) time on follow-up was 7.4 (0.5 - 20.1) months in Arm A and 6.4 (0.4 - 20.2) months in Arm B.
Clinical Benefit Rate Assessed by the IRC and the Investigator	Clinical benefit rate is defined as the percentage of participants who achieved a confirmed complete response, partial response, or durable stable disease assessed by the IRC and the Investigator per RECIST v1.1. Response evaluations were performed using computed tomography or MRI approximately every 6 weeks for the first 54 weeks and then every 12 weeks thereafter. CR: Disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or non-target) < 10 mm, and no new lesions. PR: At least a 30% decrease in the size of target lesions, with no progression of non-target lesions and no new lesions, or disappearance of target lesions with persistence of 1 or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, and no new lesions. Durable SD: Stable disease for ≥ 24 weeks. Response (CR or PR) must have been confirmed 4 weeks or later after the first response.	Up to the primary analysis data cutoff date of 01 February 2023; median (range) time on follow-up was 7.4 (0.5 - 20.1) months in Arm A and 6.4 (0.4 - 20.2) months in Arm B.
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/Quality of Life (QOL) and Physical Functioning Scores	The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1 = Not at all (best) and 4 = Very Much (worst) and 2 global health quality of life (QOL) questions answered on a 7-point scale where 1 = Very poor and 7 = Excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. Higher scores in GHS and functional scales indicate better quality of life.	Baseline, Cycle 5 Day 1 and Cycle 7 Day 1 (each cycle was 3 weeks)
Change From Baseline in EORTC Quality of Life Oesophageal Cancer Questionnaires 18 (QLQ-OES18) Dysphagia, Eating, Reflux and Pain Scales	The EORTC-QLQ-OES18 is the specific esophageal symptoms module of the QLQ-C30. QLQ-OES18 is comprised of 18 questions grouped into 4 multi-item subscales: Dysphagia (3 items), Eating (4 items), Reflux (2 items), and Pain (3 items) and 6 single item subscales (saliva swallowing, choking, dry mouth, taste, coughing, and talking). Participants indicate the extent to which they have experienced symptoms on a scale from 1 (Not at all) to 4 (Very much). Scores are calculated and transformed to a scale from 0 to 100; higher scores indicate a higher level of symptomatology or problems.	Baseline, Cycle 5 Day 1 and Cycle 7 Day 1 (each cycle was 3 weeks)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drugs, whether related to study drugs or not. An SAE is any untoward medical occurrence that, at any dose: Resulted in death; Was life-threatening; Required hospitalization or prolongation of existing hospitalization; Resulted in disability/incapacity; Was a congenital anomaly/birth defect; Was considered a significant medical AE by the Investigator based on medical judgement. AEs were considered "related" to study drugs if there was evidence to suggest a causal relationship. The investigator assessed the severity of each AE reported based upon National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0, where ≥ 3 includes severe or medically significant, life-threatening events or death related to AE. Immune-mediated AEs were diagnosed by the investigator.	From first dose of study drug until 30 days after last dose; median duration of treatment was 3.45 months in Tislelizumab + Ociperlimab arm and 2.79 months in the Tislelizumab + Placebo arm.

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Study Director, BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2021
• Primary Completion (Actual): February 1, 2023
• Study Completion (Actual): December 26, 2023

Study Registration Dates

• First Submitted: January 25, 2021
• First Submitted That Met QC Criteria: January 28, 2021
• First Posted (Actual): February 1, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 23, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Carcinoma; Carcinoma, Squamous Cell; Antineoplastic Agents, Immunological; Antineoplastic Agents; Tislelizumab
• Other Study ID Numbers: BGB-A317-A1217-203; 2020-004658-32 (EudraCT Number); CTR20213241/CTR20210243 (Other Identifier: ChinaDrugTrials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No