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

Esophageal Squamous Cell Carcinoma (ESCC) Clinical Trial

Official title:

A Randomized, Controlled, Open-label, Global Phase 3 Study Comparing the Efficacy of the Anti-PD-1 Antibody Tislelizumab (BGB-A317) Versus Chemotherapy as Second Line Treatment in Patients With Advanced Unresectable/Metastatic Esophageal Squamous Cell Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03430843
• Other study ID #: BGB-A317-302
• Secondary ID: 2017-003699-30CT
• Status: Completed
• Phase: Phase 3
• Start date: January 26, 2018
• Est. completion date: December 28, 2022

Study information

• Verified date: December 2023
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 512
• Est. completion date: December 28, 2022
• Est. primary completion date: December 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

1. Histologically confirmed diagnosis of esophageal squamous cell carcinoma (ESCC)

2. Tumor progression during or after first-line treatment for advanced unresectable / metastatic ESCC

3. At least one measurable/evaluable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 prior to randomization

Key Exclusion Criteria:

1. Receipt of 2 or more prior systemic treatments for advanced/metastatic unresectable ESCC

2. History of gastrointestinal perforation and /or fistula or aorto-esophageal fistula within 6 months prior to randomization

3. 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

4. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage

5. Received prior therapies targeting programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1)

6. 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)

7. Active brain or leptomeningeal metastasis.

8. Has active autoimmune disease or history of autoimmune diseases at high risk for relapse

9. 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

10. Known history of Human Immunodeficiency Virus (HIV)

11. Has cardiovascular risk factors

12. Pregnant or breastfeeding woman.

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma
• Esophageal Squamous Cell Carcinoma (ESCC)

Intervention

Drug:
• Tislelizumab
200 mg administered intravenously (IV)
• Paclitaxel
135-175 mg /m² administered IV , or 80-100 mg/m^2 administered IV according to local guidelines for standard of care
• Docetaxel
75 mg/m^2 administered IV or 70 mg/m^2 IV in Japan
• Irinotecan
125 mg/m^2 administered IV

Locations

Country	Name	City	State
Belgium	Imelda Ziekenhuis	Antwerp
Belgium	UZ Antwerpen	Antwerp
Belgium	Cliniques universitaires Saint-Luc	Brussels
Belgium	University Hospitals Leuven	Leuven
Belgium	Centre Hospitalier Universitaire (CHU) de Liege - Site du Sart Tilman	Liege
China	Affiliated Hospital of Hebei University	Baoding	Hebei
China	Beijing Cancer Hospital	Beijing	Beijing
China	Beijing Friendship Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	The First Hospital of Jinlin University	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha	Hunan
China	The First People's Hospital Of Changzhou	Changzhou	Jiangsu
China	Sichuan Academy of Medical Sciences& Sichuan Provincial People's Hospital	Chengdu	Sichuan
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Fujian Provincial Cancer Hospital	Fuzhou	Fujian
China	The First Affiliated Hospital of Fujian Medical University	Fuzhou	Fujian
China	The First Hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	The Sixth Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong
China	Hangzhou First People's Hospital	Hangzhou	Zhejiang
China	The First Affiliated Hospital, Zhejiang University	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Anhui Medical University - The Second Hospital	Hefei	Anhui
China	Huai'an Second People's Hospital	Huai'an	Jiangsu
China	Shandong Cancer Hospital	Jinan	Shandong
China	Yunnan Cancer Hospital - Oncology	Kunming	Yunnan
China	Shandong Linyi Tumor Hospital	Linyi	Shandong
China	Jiangxi Cancer Hospital	Nanchang	Jiangxi
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Nanjing Drum Tower Hospital	Nanjing	Jiangsu
China	Nantong Tumor Hospital	Nantong	Jiangsu
China	Fudan Cancer Hospital	Shanghai	Shanghai
China	Cancer Hospital of Shantou University Medical College	Shantou	Guangdong
China	Peking University Shenzhen Hospital	Shenzhen	Guangdong
China	Fourth Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Shanxi Provincial People's Hospital	Taiyuan	Shanxi
China	WeiFang People's Hospital	Weifang	Shandong
China	Hubei Cancer Hospital	Wuhan	Hubei
China	The Second Affiliated Hospital of Xi'an Jiaotong University(Xibei Hospital)	Xi'an	Shanxi
China	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian
China	Xiangyang Central Hospital	Xiangyang	Hubei
China	The First Affiliated Hospital of Xinxiang Medical University	Xinxiang	Henan
China	The Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu
China	Henan Cancer Hospital	Zhengzhou	Henan
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
France	CHRU Besançon	Besançon
France	CHRU de Brest Hôpital Morvan	Brest
France	Centre Georges-Francois Leclerc	Dijon
France	Center Oscar Lambret - Alliance Member	Lille
France	Hopital Prive Jean Mermoz	Lyon
France	ICM Val d'Aurelle	Montpellier
France	Comprehensive Cancer Center-Gustave Roussy	Paris
France	Hôpital Haut-Lévêque	Pessac
France	CHU de Poitiers	Poitiers
France	Centre de Lutte Contre le Cancer	Saint-Herblain
France	Clinique Sainte-Anne	Strasbourg
Germany	Charite - Universitatsmedizin Berlin /Campus Virchow Klinikum (CVK) - Med. Klinik m. S. Hamatologie, Onkologie und Tumorimmunologie (CC14)	Berlin
Germany	Universitatsklinikum Carl Gustav Carus Dresden, Medizinische Klinik und Poliklinik	Dresden
Germany	Asklepios Klinik Altona	Hamburg
Germany	Hamatologisch-Onkologische Praxis Eppendorf (HOPE)	Hamburg
Germany	Universitatsklinikum Koln, Innere Medizin I	Koln
Germany	Universitat Leipzig, UKL AoR, Universitares Krebszentrum Leipzig (UCCL)	Leipzig
Germany	Universitaetsmedizin der Johannes Gutenberg-Universitat Mainz	Mainz
Germany	Universitaetsmedizin Mannheim, II. Medizinische Klinik	Mannheim
Germany	Kliniken Nordoberpfalz, Klinikum Weiden	Weiden
Italy	PO Garibaldi-Nesima, ARNAS Garibaldi	Catania
Italy	AUSL della Romagna, Osp. degli Infermi	Faenza
Italy	Irccs Irst	Meldola
Italy	AOU - Seconda Università degli Studi di Napoli	Naples
Italy	AOU San Luigi di Orbassano	Orbassano
Italy	Ospedale Guglielmo da Saliceto, AUSL Piacenza	Piacenza
Italy	A.O.U. Pisana, Stabilimento di Santa Chiara	Pisa
Italy	AO Citta della Salute e della Scienza di Torino - Presidio O	Torino
Japan	Hyogo Cancer Center	Akashi	Hyogo
Japan	Akita University Hospital	Akita
Japan	Chiba Cancer Center	Chiba
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	National Kyushu Cancer Center	Fukuoka
Japan	Hiroshima University Hospital	Hiroshima
Japan	Kindai University Nara Hospital	Ikoma	Nara
Japan	Saitama Cancer Center	Ina	Saitama
Japan	Kagawa University Hospital	Kagawa
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	St. Marianna University School of Medicine Hospital	Kawasaki	Kanagawa
Japan	Kobe City Medical Center General Hospital	Kobe	Hyogo
Japan	Kochi Health Sciences Center	Kochi
Japan	The Cancer Institute Hospital of JFCR	Koto-Ku	Tokyo
Japan	Kyoto University Hospital	Kyoto
Japan	Shikoku Cancer Center	Matsuyama	Ehime
Japan	Shizuoka Cancer Center	Nagaizumi	Shizuoka
Japan	Osaka International Cancer Institute	Osaka
Japan	Osaka Medical College Hospital	Osaka
Japan	Osaka University Hospital	Suita	Osaka
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center - Oncology	Seoul
Korea, Republic of	Chonnam National University Hwasun Hospital	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona	Madrid
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Madrid Norte Sanchinarro	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Institut Català d'Oncologia	Madrid
Spain	Hospital Universitario Virgen de la Arrixaca	Murcia
Spain	Hospital Universitario Miguel Servet	Zaragoza
Taiwan	Changhua Christian Hospital	Changhua	NAP
Taiwan	Chang Gung Medical Foundation - Kaohsiung Chang Gung Memorial Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	Chi Mei Hospital, Liouying	Tainan
Taiwan	Chi Mei Medical Center	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
United Kingdom	Guys & St. Thomas Hospital	London
United Kingdom	Imperial NHS Trust	London
United Kingdom	Sarah Cannon Research Institute-London	London
United Kingdom	St. George's Hospital	London
United Kingdom	The Royal Marsden NHS Foundation Trust	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Mount Vernon Cancer Centre	Northwood
United Kingdom	The Royal Marsden NHS Foundation Trust - Haemato-Oncology	Sutton
United Kingdom	New Cross Hospital	Wolverhampton
United States	Henry Ford Hospital	Detroit	Michigan
United States	San Antonio Military Medical Center	Fort Sam Houston	Texas
United States	St. Joseph Heritage Healthcare	Fullerton	California
United States	Millennium Oncology	Houston	Texas
United States	University of Southern California Norris Comprehensive Cancer Center	Los Angeles	California
United States	Toledo Clinic Cancer Center	Toledo	Ohio
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Countries where clinical trial is conducted

United States,  Belgium,  China,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Spain,  Taiwan,  United Kingdom, 

References & Publications (1)

Shen L, Kato K, Kim SB, Ajani JA, Zhao K, He Z, Yu X, Shu Y, Luo Q, Wang J, Chen Z, Niu Z, Zhang L, Yi T, Sun JM, Chen J, Yu G, Lin CY, Hara H, Bi Q, Satoh T, Pazo-Cid R, Arkenau HT, Borg C, Lordick F, Li L, Ding N, Tao A, Shi J, Van Cutsem E; RATIONALE-3 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS) in the Intent-to-Treat (ITT) Analysis Set	OS is defined as the length of time from the date of randomization until the date of death due to any cause in all randomized participants	Approximately 2 years and 10 months from date of first randomization
Secondary	Overall Survival (OS) in the PDL-1 Positive Analysis Set	OS is defined as the time from the date of randomization until the date of death due to any cause in the PD-L1 positive population, defined as vCPS =10%.	Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
Secondary	Objective Response Rate (ORR) in the ITT Analysis Set	ORR is defined as the percentage of participants who had complete response (CR) or partial response (PR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1;	Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
Secondary	Overall Response Rate (ORR) in the PD-L1 Positive Analysis Sets	ORR is defined as the percentage of participants who had complete response (CR) or partial response (PR) as assessed by the investigator per RECIST v1.1;	Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
Secondary	Progression-free Survival (PFS) in the ITT Analysis Set	PFS is defined as the time from the date of randomization to the date of first documentation of disease progression assessed by the investigator per RECIST v1.1 or death, whichever occurs first; reported for the ITT analysis set	Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
Secondary	Progression-free Survival (PFS) in the PDL-1 Positive Analysis Set	PFS is defined as the time from the date of randomization to the date of first documentation of disease progression assessed by the investigator per RECIST v1.1 or death, whichever occurs first; reported for the PDL-1 Positive Analysis Set	Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
Secondary	Duration of Response (DOR) in the ITT Analysis Set	DOR is defined as the time from the first determination of an objective response until the first documentation of progression as assessed by the investigator per RECIST v1.1, or death, whichever comes first	Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
Secondary	Duration of Response (DOR) in the PDL-1 Positive Analysis Set.	DOR is defined as the time from the first determination of an objective response until the first documentation of progression as assessed by the investigator per RECIST v1.1, or death, whichever comes first	Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
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	Mean change from baseline in EORTC QLQ-C30 index score. The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of cancer participants. It includes global health status and quality of life questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes	Baseline to Cycle 6 (21 days per cycle)
Secondary	HRQoL as Assessed by EORTC QLQ-C30 in the PDL-1 Positive Analysis Set	Mean change from baseline in EORTC QLQ-C30 Index score. The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of cancer participants. It includes global health status and quality of life questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes	Baseline to Cycle 6 (21 days per cycle)
Secondary	HRQoL as Assessed by EORTC QLQ-Oesophagus Cancer Module (EORTC QLQ-OES18) Reported in ITT Analysis Set	Mean change from baseline in EORTC QLQ-OES18 index score. The EORTC QLQ-OES18 is a questionnaire that assesses overall symptoms in esophageal cancer participants. It includes questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes.	Baseline to Cycle 6 (21 days per cycle)
Secondary	HRQoL as Assessed by EORTC QLQ-OES18) in the PDL-1 Positive Analysis Set.	Mean change from baseline in EORTC QLQ-OES18 index score. The EORTC QLQ-OES18 is a questionnaire that assesses overall symptoms in esophageal cancer participants. It includes questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes.	Baseline to Cycle 6 (21 days per cycle)
Secondary	HRQoL as Assessed by European Quality of Life 5-Dimensions 5-Level Questionnaire (EQ-5D-5L) in the ITT Analysis Set	Mean change from baseline in EQ-5D-5L visual acuity score (VAS). The EQ-5D-5L measures health outcomes using a VAS to record a participant's self-rated health on a scale from 0 to 100, where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine.' A higher score indicates better health outcomes.	Baseline to Cycle 6 (21 days per cycle)
Secondary	HRQoL as Assessed by EQ-5D-5L in the PD-L1 Positive Analysis Set	Mean change from baseline in EQ-5D-5L visual acuity score (VAS). The EQ-5D-5L measures health outcomes using a VAS to record a participant's self-rated health on a scale from 0 to 100, where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine.' A higher score indicates better health outcomes.	Baseline to Cycle 6 (21 days per cycle)
Secondary	Number of Participants Experiencing Adverse Events (AEs)	Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), which includes laboratory tests, physical exams, electrocardiogram results and vital signs	From the first dose date to 30 days after the last dose date; up to approximately 4 years and 11 months