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

BeiGene125 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

125

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

TislelizumabBIOLOGICAL

Tislelizumab is a monoclonal antibody formulated for intravenous injection.

OciperlimabBIOLOGICAL

Ociperlimab is a monoclonal antibody formulated for intravenous injection.

PlaceboDRUG

Ociperlimab placebo injection is a sterile, preservative-free solution for infusion formulated in the same buffer as ociperlimab active drug.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (86)

Outcomes

Primary Outcomes

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.

Time frame: 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 Outcomes

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.

Time frame: 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.

Data from ClinicalTrials.gov

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Anhui Provincial Cancer Hospital

Hefei, Anhui, China

Quanzhou First Hospital of Fujian Province

Quanzhou, Fujian, China

First Affiliated Hospital of Xiamen University

Xiamen, Fujian, China

Lanzhou University Second Hospital

Gansu, Gansu, China

Guangdong Provincial Hospital of Chinese Medicine

Guangzhou, Guangdong, China

Meizhou Hospital Affiliated to Sun Yat-sen University

Guangzhou, Guangdong, China

Hainan Third People's Hospital

Sanya, Hainan, China

Nantong Tumor Hospital

Nantong, Jiangsu, China

Affiliated Hospital of Jiangnan University

Wuxi, Jiangsu, China

General Hospital of Ningxia Medical University

Yinchuan, Ningxia, China

...and 76 more locations

Time frame: 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.

Time frame: 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.

Time frame: 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.

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.