Non-small Cell Lung Cancer, NSCLC
Conditions
Keywords
Locally Advanced, Unresectable, Metastatic, Tislelizumab, BGB-A317, Ociperlimab, BGB-A1217, Pembrolizumab, Anti-TIGIT
Brief summary
The purpose of this study is to evaluate the efficacy and safety of ociperlimab + tislelizumab compared with that of pembrolizumab in adults with high levels of programmed cell death ligand-1 (PD-L1), locally advanced/recurrent or untreated metastatic non-small cell lung cancer (NSCLC).
Interventions
DRUGTislelizumab
Tislelizumab is a monoclonal antibody formulated for intravenous injection.
DRUGOciperlimab
Ociperlimab is a monoclonal antibody formulated for intravenous injection.
DRUGPembrolizumab
Pembrolizumab is a monoclonal antibody formulated for intravenous injection.
DRUGPlacebo
Placebo infusions will consist of a sterile, normal saline solution.
Sponsors
BeiGene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Histologically or cytologically documented locally advanced or recurrent non-small cell lung cancer (NSCLC) that is not eligible for curative surgery and/or definitive radiotherapy with or without chemoradiotherapy, or metastatic-nonsquamous or squamous NSCLC. 2. No prior systemic treatment for metastatic NSCLC. 3. Agreement to provide archival tissue or fresh biopsy (if archival tissue is not available). 4. Tumors with PD-L1 expressed in ≥ 50% tumor cells. 5. At least 1 measurable lesion as defined per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. 6. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1. Key
Exclusion criteria
1. Known mutations in the epidermal growth factor receptor (EGFR) gene, anaplastic lymphoma kinase (ALK) fusion oncogene, BRAF V600E, or ROS1. 2. Prior therapy with an anti-programmed cell death protein (anti-PD)-1, anti-PD-ligand (L)-1, anti-PD-ligand-2, anti-T-cell immunoglobulin and ITIM (anti-TIGIT) domain, or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways. 3. Active leptomeningeal disease or uncontrolled, untreated brain metastasis. 4. Active autoimmune diseases or history of autoimmune diseases that may relapse. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in Arms A and B | From randomization until the end of the study. Maximum time on study was 45.0 months | OS is defined as the time from the date of randomization to the date of death due to any cause. Median OS was estimated using the Kaplan-Meier method. OS was a pre-specified primary endpoint for Arms A and B only. |
| Safety Run-In Substudy: Number of Participants Experiencing Adverse Events (AEs) | From first dose of study drug to 30 days after last dose. Maximum treatment duration was 12.45 months. | The severity of AEs was determined according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0). AEs were graded on a scale of Grade 1 to Grade 5, with Grade 1 being the least severe and Grade 5 being the most severe. An AE is defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a study drug, whether considered related to study drug or not. A serious adverse event (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. |
| Safety Run-In Substudy: Serum Concentration of Ociperlimab | Cycle 1 Day 1 (C1D1) Postdose (30 minutes after end of infusion), 24 and 72 Hours Postdose; C1D8; C1D15; C2D1 Predose and Postdose; C5D1 Predose; C5D1 Postdose; C5D8; C5D15; C6D1 Predose and Postdose; C9D1 Predose; C13D1 Predose; End of Treatment. | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) for Arm A Versus Arm B As Assessed By the Investigator | Response was assessed every 9 weeks from randomization for the first 52 weeks and then every 12 weeks thereafter, up to 45.0 months | ORR is defined as the percentage of participants with a documented, confirmed complete response or partial response per RECIST v1.1. ORR was a pre-specified secondary endpoint for Arms A and B only. Complete response is defined as disappearance of all target lesions, disappearance of all nontarget lesions and normalization of tumor marker level, and no new lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, no unequivocal progression of non-target lesions, and no new lesions. |
| Overall Response Rate (ORR) for Safety Run-In Substudy As Assessed By the Investigator | Response was assessed every 9 weeks from randomization for the first 52 weeks and then every 12 weeks thereafter, up to 38.9 months | ORR is defined as the percentage of participants with a documented, confirmed complete response or partial response per RECIST v1.1. |
| Duration Of Response (DOR) for Arm A Versus Arm B As Assessed By the Investigator | Up to 45.0 months | DOR is defined as the time from the first determination of an objective response per RECIST v1.1 until the first documentation of progression or death, whichever occurs first. Median DOR was estimated using the Kaplan-Meier method. DOR was a pre-specified secondary endpoint for Arms A and B only. |
| Duration Of Response (DOR) for Safety Run-In Substudy As Assessed By the Investigator | Up to 38.9 months | DOR is defined as the time from the first determination of an objective response per RECIST v1.1 until the first documentation of progression or death, whichever occurs first. Median DOR was estimated using the Kaplan-Meier method. |
| Change From Baseline in Global Health Status (GHS)/Quality of Life (QoL), Physical Functioning, and Pain Scores: European Organization For Research And Treatment Of Cancer Quality Of Life Questionnaire Core 30 (EORTC QLQ-C30) in Arms A and B | Baseline to Cycle 5 and Cycle 7, each cycle was 3 weeks | The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical, role, emotional, cognitive, and social functioning), 1 GHS 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 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. Lower scores in symptom scales indicate better quality of life. Included in this outcome measure were evaluation of GHS/QoL, physical functioning, and fatigue. This was a pre-specified secondary endpoint for Arms A and B only. |
| Change From Baseline in EORTC Lung Cancer Module Quality of Life Questionnaire Lung Cancer 13 (QLQ-LC13) Index Score, Dyspnea, Coughing, Hemoptysis, Pain in Chest, Pain in Arms/Shoulders, and Peripheral Neuropathy Scores in Arms A and B | Baseline to Cycle 5 and Cycle 7, each cycle was 3 weeks | The EORTC QLQ-LC13 is the lung cancer module of the QLQ-C30 and measures lung cancer-specific disease and treatment symptoms. It includes 13 questions about specific symptoms in which participants respond based on a 4-point scale, where 1 is "not at all" and 4 is "very much". Raw scores are transformed into a 0 to 100 scale via linear transformation. The symptom index scale was calculated by taking the mean of all symptom scale scores, and ranges from 0 to 100. Lower scores indicate an improvement in symptoms. This was a pre-specified secondary endpoint for Arms A and B only. |
| Change From Baseline in European Quality of Life-5 Level- 5 Dimension (EQ-5D-5L) Visual Analog Scale in Arms A and B | Baseline to Cycle 5 and Cycle 7, each cycle was 3 weeks | The EQ-5D-5L comprises a descriptive module that includes five dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) and a Visual Analog Scale (VAS). The VAS records a participant's self-rated health on a vertical scale from 0 to 100, where 0 is 'the worst health you can imagine' and 100 is 'the best health you can imagine'. A higher score indicates better health outcomes. This was a pre-specified secondary endpoint for Arms A and B only. |
| Time To Deterioration (TTD) in Arms A and B Based on QLQ-LC13 Index Score, Cough, Chest Pain, Dyspnea, Hemoptysis, Arm or Shoulder Pain, and Peripheral Neuropathy | Up to 45.0 months | TTD is defined as the time from randomization to the first occurrence of worsening scores of ≥ 10 points from baseline for 2 consecutive assessments or 1 assessment followed by death from any cause. TTD was estimated using the Kaplan-Meier method. TTD was a pre-specified secondary endpoint for Arms A and B only. |
| Number Of Participants Experiencing Adverse Events (AEs) in Arm A | From first dose of study drug up to 30 days after last dose (or 90 days for immune-mediated AEs); maximum treatment duration was 45.0 months | The severity of AEs was determined according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0). AEs were graded on a scale of Grade 1 to Grade 5, with Grade 1 being the least severe and Grade 5 being the most severe. An AE is defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a study drug, whether considered related to study drug 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. This was a pre-specified secondary endpoint for Arm A only. |
| Time To Deterioration (TTD) in Arms A and B Based on QLQ-C30 GHS/QoL Score, Physical Functioning, and Fatigue | Up to 45.0 months | TTD is defined as the time from randomization to the first occurrence of worsening scores of ≥10 points from baseline for 2 consecutive assessments or 1 assessment followed by death from any cause. TTD was estimated using the Kaplan-Meier method. TTD was a pre-specified secondary endpoint for Arms A and B only. |
| Safety Run-In Substudy: Participants With Anti-Drug Antibodies | Up to 38.9 months | — |
| Progression-free Survival (PFS) for Arm A Versus Arm B As Assessed By the Investigator | Up to 45.0 months | PFS is defined as the time from the date of randomization to the date of the first objectively documented tumor progression per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death, whichever occurs first. Median PFS was estimated using the Kaplan-Meier method. PFS was a pre-specified secondary endpoint for Arms A and B only. Progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, unequivocal progression of existing non-target lesions, or new lesions. |
| Progression-free Survival (PFS) for Safety Run-In Substudy As Assessed By the Investigator | Up to 38.9 months | PFS is defined as the time from the date of randomization to the date of the first objectively documented tumor progression per RECIST v1.1, or death, whichever occurs first. Median PFS was estimated using the Kaplan-Meier method. |
Countries
Argentina, Australia, Brazil, China, France, Georgia, Germany, Italy, Japan, Netherlands, Poland, Russia, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United States
Participant flow
Recruitment details
Participants were enrolled at 200 centers in 20 countries globally. A safety run-in substudy was conducted to evaluate preliminary safety and tolerability in Japanese participants before Japanese participants were randomized into the study.
Pre-assignment details
Eligible participants were randomized in an approximately 5:5:2 ratio to receive different treatments in Arms A, B, or C. Randomization was stratified by histology (squamous vs non-squamous) and region (Asia vs non-Asia).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 374 Participants |
| Age, Categorical Between 18 and 65 years | 295 Participants |
| Age, Continuous | 65.43 years STANDARD_DEVIATION 9.698 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 282 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race/Ethnicity, Customized Asian | 353 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants |
| Race/Ethnicity, Customized Not Reported | 0 Participants |
| Race/Ethnicity, Customized Other | 2 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants |
| Race/Ethnicity, Customized White | 309 Participants |
| Region of Enrollment Argentina | 0 participants |
| Region of Enrollment Australia | 4 participants |
| Region of Enrollment Brazil | 2 participants |
| Region of Enrollment China | 106 participants |
| Region of Enrollment France | 0 participants |
| Region of Enrollment Georgia | 25 participants |
| Region of Enrollment Germany | 0 participants |
| Region of Enrollment Italy | 2 participants |
| Region of Enrollment Japan | 58 participants |
| Region of Enrollment Mexico | 0 participants |
| Region of Enrollment Netherlands | 9 participants |
| Region of Enrollment Poland | 5 participants |
| Region of Enrollment Russia | 3 participants |
| Region of Enrollment South Korea | 10 participants |
| Region of Enrollment Spain | 29 participants |
| Region of Enrollment Taiwan | 0 participants |
| Region of Enrollment Thailand | 8 participants |
| Region of Enrollment Turkey | 26 participants |
| Region of Enrollment Ukraine | 5 participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 57 Participants |
| Sex: Female, Male Male | 536 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 130 / 287 | 137 / 287 | 43 / 88 | 5 / 7 |
| other Total, other adverse events | 277 / 286 | 267 / 287 | 79 / 87 | 7 / 7 |
| serious Total, serious adverse events | 150 / 286 | 113 / 287 | 41 / 87 | 4 / 7 |
Outcome results
None listed