Locally Advanced, Unresectable, or Metastatic Nonsmall Cell Lung Cancer (NSCLC), Nonsmall Cell Lung Cancer, Stage IIIB, Nonsmall Cell Lung Cancer, Stage IV
Conditions
Keywords
metastatic, Lung Cancer, Non-Squamous, Ociperlimab, Tislelizumab, Anti-PD-1, BGB-A317, BGB-A1217, Anti-TIGIT
Brief summary
This study aimed to evaluate the safety and effectiveness of ociperlimab combined with tislelizumab and chemotherapy, compared to tislelizumab and chemotherapy alone, in participants with non-small cell lung cancer (NSCLC) that was locally advanced, could not be removed by surgery, or had spread to other parts of the body.
Interventions
DRUGOciperlimab
900 mg intravenously (IV) once every 3 weeks (Q3W)
DRUGTislelizumab
200 mg IV Q3W
DRUGCarboplatin
Area under the concentration-time curve (AUC) of 5 or 6, administered on Day 1 of each 21-day cycle
DRUGPaclitaxel
75 or 200 mg per square meter (mg/m²) of body surface area, administered on Day 1 of each 21-day cycle
DRUGNab paclitaxel
100 mg/m², administered intravenously on Days 1, 8, and 15 of each 21-day cycle
DRUGCisplatin
75 mg/m², administered intravenously on Day 1 of each 21-day cycle
DRUGPemetrexed
500 mg/m² administered intravenously on Day 1 of each 21-day cycle
DRUGPlacebo
Administered intravenously Q3W to match ociperlimab
Sponsors
BeiGene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Participants had histologically or cytologically confirmed locally advanced or recurrent non-small cell lung cancer (NSCLC) that was not eligible for curative surgical resection and/or definitive radiotherapy, with or without chemotherapy. Alternatively, participants had metastatic non-squamous or squamous NSCLC. 2. Participants had not received any prior systemic therapy for locally advanced or metastatic squamous or non-squamous NSCLC, including but not limited to chemotherapy or targeted therapies. Those who had previously received neoadjuvant or adjuvant chemotherapy, or chemoradiotherapy with curative intent for non-metastatic disease, were required to have experienced a disease-free interval of at least 6 months from the last dose of chemotherapy and/or concurrent radiotherapy prior to randomization. 3. Archival tumor tissue or a fresh biopsy (if archival tissue was unavailable) was required for programmed death-ligand 1 (PD-L1) level assessment and retrospective biomarker analyses. Only participants with evaluable PD-L1 results were considered eligible. 4. Participants were required to have had at least one measurable lesion as assessed by the investigator in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. 5. Participants had an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. Key
Exclusion criteria
1. Participants were excluded if they had known mutations in any of the following genes: * Epidermal Growth Factor Receptor (EGFR): For participants with non-squamous NSCLC and unknown EGFR mutation status, tissue-based EGFR testing (performed either locally or at a central laboratory) or an endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)-based EGFR test was required prior to enrollment. Those found to harbor EGFR-sensitizing mutations were excluded. * Anaplastic Lymphoma Kinase (ALK) fusion oncogene. * B-Raf Proto-Oncogene (BRAF) V600E mutation. * ROS Proto-Oncogene 1 (ROS1) rearrangement. 2. Participants who had received prior treatment with EGFR inhibitors, ALK inhibitors, or other targeted therapies for known driver mutations. 3. Participants who had received any prior therapies targeting T-cell costimulatory or checkpoint pathways (e.g., programmed cell death protein 1 \[PD-1\], programmed death-ligand 1 \[PD-L1\], or cytotoxic T-lymphocyte-associated protein 4 \[CTLA-4\]) for metastatic NSCLC were excluded. 4. Participants who had any condition requiring systemic treatment with corticosteroids at a dose greater than 10 mg of prednisone (or equivalent) daily, or other immunosuppressive medications within 14 days prior to randomization. 5. Participants who had an active infection, including but not limited to tuberculosis, requiring systemic antibacterial, antifungal, or antiviral treatment within 14 days prior to randomization were excluded. Note: Additional protocol-defined inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | From randomization up to the final efficacy analysis data cut-off date of 04 September 2024; Up to 33 months | PFS was defined as the time from randomization to the first objectively documented disease progression as assessed by the investigator per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) or death from any cause, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From randomization up to the final efficacy analysis data cut-off date of 04 September 2024; Up to 33 months | Objective response rate is defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 Tumor assessments. CR is defined as the disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Duration of Response (DOR) | From randomization up to the final efficacy analysis data cut-off date of 04 September 2024; Up to 33 months | DOR was defined as the time from the first documented objective response to documented radiological disease progression as assessed by the investigator using RECIST v1.1, or death from any cause, whichever occurred first. Median DOR was estimated using the Kaplan-Meier method. Progressive disease is captured as at least a 20% increase in the sum of diameters of target lesions, using the smallest sum on study as the reference (including the baseline sum if it was the smallest). In addition to the 20% relative increase, the sum also had to show an absolute increase of at least 5 mm. |
| Overall Survival (OS) | From randomization up to the final efficacy analysis data cut-off date of 04 September 2024; Up to 33 months | OS was defined as the time from randomization to the documented date of death for participants who died on or before the clinical cutoff date. Median OS was calculated using the Kaplan-Meier method. Data for participants who were alive at the clinical cutoff date were censored at their last known alive date, defined as either the clinical cutoff date for those still on treatment or the most recent available date confirming they were alive, whichever occurred first. |
| Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From first dose of study drug to 30 days after last dose, up to the study completion date cut-off date of 04 September 2024 (up to 32.4 months) | The number of participants who experienced TEAEs and SAEs was reported. An adverse event refers to any unintended or unfavorable sign, symptom, or condition (including abnormal lab results) that occurs during the study, regardless of whether it is linked to the study drug. Investigators evaluated the severity of each adverse event according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5. |
Countries
Australia, Austria, China, France, Greece, South Korea, Spain, United States
Participant flow
Recruitment details
This study was conducted at 75 study centers in 8 countries (China, South Korea, United States of America, Australia, France, Spain, Austria, Greece).
Pre-assignment details
Eligible participants were randomized in a 1:1 ratio to receive either ociperlimab or placebo treatment, plus tislelizumab and chemotherapy. Randomization was stratified by histology (squamous versus non--squamous), and programmed cell death protein ligand-1 (PD-L1) expression.
Participants by arm
| Arm | Count |
|---|---|
| Arm A (O+T+C) Ociperlimab (900 mg IV), tislelizumab (200 mg IV), and histology-based chemotherapy | 136 |
| Arm B (P+T+C) Placebo, tislelizumab (200 mg IV), and histology-based chemotherapy | 136 |
| Total | 272 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 63 | 70 |
| Overall Study | Lost to Follow-up | 4 | 2 |
| Overall Study | Physician Decision | 2 | 4 |
| Overall Study | Withdrawal by Subject | 10 | 10 |
Baseline characteristics
| Characteristic | Total | Arm B (P+T+C) | Arm A (O+T+C) |
|---|---|---|---|
| Age, Continuous | 63.90 years STANDARD_DEVIATION 8.697 | 63.77 years STANDARD_DEVIATION 9.366 | 64.02 years STANDARD_DEVIATION 8.006 |
| Histology Non-Squamous | 161 Participants | 80 Participants | 81 Participants |
| Histology Squamous | 111 Participants | 56 Participants | 55 Participants |
| Programmed Death-Ligand 1 (PD-L1) Expressio 1-49% of Tumor Cells | 84 Participants | 42 Participants | 42 Participants |
| Programmed Death-Ligand 1 (PD-L1) Expressio < 1% of tumor cells | 115 Participants | 58 Participants | 57 Participants |
| Programmed Death-Ligand 1 (PD-L1) Expressio > 50% of Tumor Cells | 73 Participants | 36 Participants | 37 Participants |
| Race/Ethnicity, Customized Asian | 207 Participants | 102 Participants | 105 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 5 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 246 Participants | 123 Participants | 123 Participants |
| Race/Ethnicity, Customized Not Reported | 15 Participants | 7 Participants | 8 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 48 Participants | 25 Participants | 23 Participants |
| Sex: Female, Male Female | 54 Participants | 32 Participants | 22 Participants |
| Sex: Female, Male Male | 218 Participants | 104 Participants | 114 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 63 / 136 | 70 / 136 |
| other Total, other adverse events | 132 / 135 | 132 / 136 |
| serious Total, serious adverse events | 63 / 135 | 74 / 136 |
Outcome results
Primary
Progression-free Survival (PFS)
PFS was defined as the time from randomization to the first objectively documented disease progression as assessed by the investigator per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) or death from any cause, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method.
Time frame: From randomization up to the final efficacy analysis data cut-off date of 04 September 2024; Up to 33 months
Population: Intent-To-Treat Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A (O+T+C) | Progression-free Survival (PFS) | 8.2 Months |
| Arm B (P+T+C) | Progression-free Survival (PFS) | 8.1 Months |
p-value: 0.469895% CI: [0.74, 1.33]Log Rank
Secondary
Duration of Response (DOR)
DOR was defined as the time from the first documented objective response to documented radiological disease progression as assessed by the investigator using RECIST v1.1, or death from any cause, whichever occurred first. Median DOR was estimated using the Kaplan-Meier method. Progressive disease is captured as at least a 20% increase in the sum of diameters of target lesions, using the smallest sum on study as the reference (including the baseline sum if it was the smallest). In addition to the 20% relative increase, the sum also had to show an absolute increase of at least 5 mm.
Time frame: From randomization up to the final efficacy analysis data cut-off date of 04 September 2024; Up to 33 months
Population: The analysis included only intent-to-treat participants with a confirmed complete or partial response per RECIST v1.1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A (O+T+C) | Duration of Response (DOR) | 10.4 months |
| Arm B (P+T+C) | Duration of Response (DOR) | 11.2 months |
Secondary
Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
The number of participants who experienced TEAEs and SAEs was reported. An adverse event refers to any unintended or unfavorable sign, symptom, or condition (including abnormal lab results) that occurs during the study, regardless of whether it is linked to the study drug. Investigators evaluated the severity of each adverse event according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.
Time frame: From first dose of study drug to 30 days after last dose, up to the study completion date cut-off date of 04 September 2024 (up to 32.4 months)
Population: The Safety Analysis Set included all randomized participants who received at least one dose of the study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A (O+T+C) | Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Number of participants with any TEAEs | 134 Participants |
| Arm A (O+T+C) | Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Number of participants with SAEs | 63 Participants |
| Arm B (P+T+C) | Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Number of participants with any TEAEs | 135 Participants |
| Arm B (P+T+C) | Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Number of participants with SAEs | 74 Participants |
Secondary
Objective Response Rate (ORR)
Objective response rate is defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 Tumor assessments. CR is defined as the disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From randomization up to the final efficacy analysis data cut-off date of 04 September 2024; Up to 33 months
Population: Intent-To-Treat Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A (O+T+C) | Objective Response Rate (ORR) | 41.9 percentage of participants |
| Arm B (P+T+C) | Objective Response Rate (ORR) | 47.8 percentage of participants |
95% CI: [0.47, 1.26]
Secondary
Overall Survival (OS)
OS was defined as the time from randomization to the documented date of death for participants who died on or before the clinical cutoff date. Median OS was calculated using the Kaplan-Meier method. Data for participants who were alive at the clinical cutoff date were censored at their last known alive date, defined as either the clinical cutoff date for those still on treatment or the most recent available date confirming they were alive, whichever occurred first.
Time frame: From randomization up to the final efficacy analysis data cut-off date of 04 September 2024; Up to 33 months
Population: Intent-To-Treat Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A (O+T+C) | Overall Survival (OS) | 20.6 Months |
| Arm B (P+T+C) | Overall Survival (OS) | 19.4 Months |
95% CI: [0.67, 1.34]