Cervical Cancer
Conditions
Brief summary
This study tested how well and how safely the drug tislelizumab, given either alone or with another drug called ociperlimab (BGB-A1217), worked in people with cervical cancer that had come back or spread after previous treatments. The study included two groups and took place at multiple medical centers.
Interventions
BIOLOGICALTislelizumab
200 mg administered intravenously once every 3 weeks on day 1 of each cycle
BIOLOGICALOciperlimab
900 mg administered intravenously once every 3 weeks on day 1 of each cycle
Sponsors
BeiGene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix. 2. Progression on or after one or more lines of chemotherapy for management of recurrent or metastatic disease and is not amenable to curative treatment (eg, systemic chemotherapy, surgery, or radiotherapy). 3. Measurable disease as assessed by RECIST v1.1. Note: A lesion in an area subjected to prior loco-regional therapy, including previous radiotherapy, is not considered measurable unless there has been demonstrated progression in the lesion since the therapy as defined by RECIST v1.1. 4. Participants must submit qualified archival tumor tissue (formalin-fixed paraffin-embedded block containing tumor \[preferred\] or approximately 15 \[at least 6\] unstained slides) with an associated pathology report, or agree to a tumor biopsy for determination of Programmed death-ligand 1 (PD-L1) expression and other biomarker analyses (fresh tumor biopsies are strongly recommended at baseline in participants with readily accessible tumor lesions and who consent to the biopsies). 5. Participant must have adequate organ function as indicated by the screening laboratory values obtained within 7 days before the first study treatment.
Exclusion criteria
1. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, TIGIT or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways. 2. Any active malignancy ≤ 2 years before first dose of study drug except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of breast). 3. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage (recurrence within 2 weeks of intervention). 4. Any major surgical procedure ≤ 28 days before first dose of study drug. Participants must have recovered adequately from the toxicity and/or complications from the intervention before the first dose of study drug. 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohort 1: Objective Response Rate (ORR) Assessed by an Independent Review Committee (IRC) in PD-L1-Positive Participants | Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up duration was 7.36 months for Cohort 1. | ORR is defined as the percentage of participants who had confirmed complete response (CR) or partial response (PR) as assessed by the IRC per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). PD-L1-positive refers to participants whose tumors had a PD-L1 TAP score ≥ 5%. |
| Cohort 1: ORR Assessed by the IRC in All Treated Participants | Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up duration was 7.36 months for Cohort 1. | ORR is defined as the percentage of participants who had a confirmed CR or PR as assessed by the IRC per RECIST v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR as Assessed by the Investigator in All Treated Participants | Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up duration was 7.36 months for Cohort 1 and 10.40 months for Cohort 2. | ORR is defined as the percentage of participants who had a confirmed CR or PR as assessed by the investigator per RECIST v1.1. |
| Duration of Response (DOR) Assessed by the IRC | Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up duration was 7.36 months for Cohort 1 and 10.40 months for Cohort 2. | DOR is defined as the time from the first confirmed objective response until the first documentation of progression or death, whichever occurred first, assessed by the IRC according to RECIST v1.1 in the Safety Analysis Set. |
| Duration of Response (DOR) Assessed by the Investigator | Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up duration was 7.36 months for Cohort 1 and 10.40 months for Cohort 2. | DOR is defined as the time from the first confirmed objective response until the first documentation of progression or death, whichever comes first, assessed by the investigator according to RECIST v1.1 in the Safety Analysis Set. Data was based on number of responders. |
| Progression Free Survival (PFS) | Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up duration was 7.36 months for Cohort 1 and 10.40 months for Cohort 2. | Defined as the time from the date of first dose of study drug to the date of first documentation of disease progression or death, whichever occurred first as assessed by both the IRC and the investigator's review per RECIST v1.1 in the Safety Analysis Set. |
| Time to Response (TTR) Assessed by the IRC | Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up was 7.36 months for Cohort 1 and 10.40 months for Cohort 2. | TTR is defined as the time from the date of first dose of study drug to the first documentation of response as assessed by the IRC per RECIST v1.1, in the Safety Analysis Set. |
| Time to Response (TTR) Assessed by the Investigator | Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up was 7.36 months for Cohort 1 and 10.40 months for Cohort 2. | TTR is defined as the time from the date of first dose of study drug to the first documentation of response as assessed by the investigator per RECIST v1.1, in the Safety Analysis Set. |
| Disease Control Rate (DCR) | Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up duration was 7.36 months for Cohort 1 and 10.40 months for Cohort 2. | DCR is defined as the percentage of participants who achieve CR, PR, or stable disease (SD) as assessed by both the IRC and investigator per RECIST v1.1 in the Safety Analysis Set. |
| Clinical Benefit Rate (CBR) | Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up duration was 7.36 months for Cohort 1 and 10.40 months for Cohort 2. | Defined as the percentage of participants who achieve CR, PR, or durable SD (SD ≥ 24 weeks) as assessed by both the IRC and investigator per RECIST v1.1 in the Safety Analysis Set. |
| Cohort 2: Objective Response Rate (ORR) Assessed by an Independent Review Committee in All Treated Participants | Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up duration was 10.40 months for Cohort 2. | ORR is defined as the percentage of participants who had confirmed complete response (CR) or partial response (PR) as assessed by the IRC per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). |
| Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life, Physical Functioning, and Pain Scores | Baseline to Cycles 3 and 5 ( Each cycle was 21 days) | 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. Lower scores in symptom scales indicate better quality of life. |
| Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Symptom Specific Scale for Cervical Cancer (EORTC QLQ-CX24) Index Score | Baseline to Cycles 3 and 5 ( Each cycle was 21 days) | QLQ-CX24 is the cervical cancer module of the QLQ-C30. CX24 is comprised of 24 questions grouped into 3 symptom scales and 6 single symptom items. Each question is answered on a scale from 1 (not at all) to 4 (very much). The scales include Symptom Experience (11 items), Body Image (3 items) and Sexual/vaginal Functioning (4 items). The single symptom items include Lymphedema, Peripheral Neuropathy, Menopausal Symptoms, Sexual Worry, Sexual Activity and Sexual Enjoyment. Raw scores are transformed into a 0 to 100 scale via linear transformation. The Index score is calculated as the average of the 3 symptom scales and 6 single item scores. Lower scores indicate better HRQoL. |
| Number of Participants Experiencing Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | From the first dose of study drug to 30 days after the last dose; maximum treatment exposure was 23.5 months. | 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 considered 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 (eg, may jeopardize the patient or may require medical/surgical intervention to prevent one of the outcomes listed above). |
| Serum Ociperlimab (BGB-A1217) Concentrations at Specified Timepoints | Day 1 of Cycles 1, 2, 5, 9, and 17 (each cycle was 21 days) | The timepoints are defined as predose (within 60 minutes before starting infusion) and postdose (within 30 minutes after the end of infusion). |
| Serum Tislelizumab Concentrations at Specified Timepoints | Day 1 of Cycles 1, 2, 5, 9, and 17 (each cycle is 21 days) | The timepoints are defined as predose (within 60 minutes before starting infusion) and postdose (within 30 minutes after the end of infusion). |
| Number of Participants Who Developed Positive Anti-drug Antibodies (ADAs) to Ociperlimab | Samples for ADA analysis were collected predose on Day 1 of Cycles 1, 2, 5, 9 and 17, and at the Safety Follow-up Visit (30 days after last dose) up to the immunogenicity data cut-off date of June 1, 2023 (approximately 21 months). | Number and percentage of participants who developed detectable ADAs to ociperlimab during the treatment period. |
| Number of Participants Who Developed Anti-drug Antibodies (ADAs) to Tislelizumab | Samples for ADA analysis were collected predose on Day 1 of Cycles 1, 2, 5, 9 and 17, and at the Safety Follow-up Visit (30 days after last dose), up to the immunogenicity data cut-off date of June 1, 2023 (approximately 21 months). | Number and percentage of participants who developed detectable ADAs during the treatment period. |
| Overall Survival (OS) | Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up duration was 7.36 months for Cohort 1 and 10.40 months for Cohort 2. | Overall survival is defined as the time from the date of randomization to the date of death due to any cause. Median OS was estimated using Kaplan-Meier methodology. |
| ORR Assessed by the Investigator in PD-L1-Positive Participants | Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up duration was 7.36 months for Cohort 1 and 10.40 months for Cohort 2. | ORR is defined as the percentage of participants who had confirmed CR or PR as assessed by the investigator per RECIST v1.1 in the PD-L1 Score \>= 5% Safety Analysis Set. |
Countries
Bulgaria, China, Poland, Russia, South Korea, Taiwan, Thailand, Ukraine
Participant flow
Recruitment details
Participants were enrolled in multiple study centers in China, South Korea, and Europe.The first participant dosed was on March 3rd, 2021 and the last participant completed on August 31st, 2023.
Pre-assignment details
The study was composed of an initial screening phase (up to 28 days), a treatment phase, an end of treatment visit, an on-site Safety Follow-up Visit, and 2 Safety Follow-up Visits by telephone after the last dose of study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Ociperlimab + Tislelizumab Participants received tislelizumab 200 mg IV and ociperlimab 900 mg IV once every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. | 138 |
| Cohort 2: Tislelizumab Participants received tislelizumab 200 mg IV once every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. | 40 |
| Total | 178 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 79 | 19 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Sponsor Ended Study | 47 | 18 |
| Overall Study | Withdrawal by Subject | 10 | 2 |
Baseline characteristics
| Characteristic | Cohort 1: Ociperlimab + Tislelizumab | Total | Cohort 2: Tislelizumab |
|---|---|---|---|
| Age, Continuous | 52.7 years STANDARD_DEVIATION 10.28 | 52.3 years STANDARD_DEVIATION 10.15 | 51.2 years STANDARD_DEVIATION 9.74 |
| Eastern Cooperative Oncology Group Performance Status 0 | 53 Participants | 69 Participants | 16 Participants |
| Eastern Cooperative Oncology Group Performance Status 1 | 85 Participants | 109 Participants | 24 Participants |
| Programmed Death-Ligand 1 (PD-L1) Expression Not Evaluable | 1 Participants | 1 Participants | 0 Participants |
| Programmed Death-Ligand 1 (PD-L1) Expression PD-L1 Score < 5% | 53 Participants | 73 Participants | 20 Participants |
| Programmed Death-Ligand 1 (PD-L1) Expression PD-L1 Score >= 5% | 84 Participants | 104 Participants | 20 Participants |
| Race/Ethnicity, Customized Asian | 117 Participants | 154 Participants | 37 Participants |
| Race/Ethnicity, Customized White | 21 Participants | 24 Participants | 3 Participants |
| Region of Enrollment Bulgaria | 2 participants | 2 participants | 0 participants |
| Region of Enrollment China | 71 participants | 88 participants | 17 participants |
| Region of Enrollment Poland | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Russia | 8 participants | 11 participants | 3 participants |
| Region of Enrollment South Korea | 30 participants | 38 participants | 8 participants |
| Region of Enrollment Taiwan | 10 participants | 16 participants | 6 participants |
| Region of Enrollment Thailand | 6 participants | 12 participants | 6 participants |
| Region of Enrollment Ukraine | 10 participants | 10 participants | 0 participants |
| Sex/Gender, Customized Female | 138 Participants | 178 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 79 / 138 | 19 / 40 |
| other Total, other adverse events | 128 / 138 | 37 / 40 |
| serious Total, serious adverse events | 61 / 138 | 17 / 40 |
Outcome results
Primary
Cohort 1: Objective Response Rate (ORR) Assessed by an Independent Review Committee (IRC) in PD-L1-Positive Participants
ORR is defined as the percentage of participants who had confirmed complete response (CR) or partial response (PR) as assessed by the IRC per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). PD-L1-positive refers to participants whose tumors had a PD-L1 TAP score ≥ 5%.
Time frame: Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up duration was 7.36 months for Cohort 1.
Population: The PD-L1 Score ≥ 5% Safety Analysis Set includes all treated participants whose tumors had PD-L1 TAP Score ≥ 5%.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Ociperlimab + Tislelizumab | Cohort 1: Objective Response Rate (ORR) Assessed by an Independent Review Committee (IRC) in PD-L1-Positive Participants | 26.2 percentage of participants |
p-value: 0.0054Binomial Exact Test
Primary
Cohort 1: ORR Assessed by the IRC in All Treated Participants
ORR is defined as the percentage of participants who had a confirmed CR or PR as assessed by the IRC per RECIST v1.1.
Time frame: Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up duration was 7.36 months for Cohort 1.
Population: The Safety Analysis Set includes all participants who received at least 1 dose of any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Ociperlimab + Tislelizumab | Cohort 1: ORR Assessed by the IRC in All Treated Participants | 22.5 percentage of participants |
p-value: 0.0127Binomial Exact Test
Secondary
Clinical Benefit Rate (CBR)
Defined as the percentage of participants who achieve CR, PR, or durable SD (SD ≥ 24 weeks) as assessed by both the IRC and investigator per RECIST v1.1 in the Safety Analysis Set.
Time frame: Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up duration was 7.36 months for Cohort 1 and 10.40 months for Cohort 2.
Population: The Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Ociperlimab + Tislelizumab | Clinical Benefit Rate (CBR) | IRC | 29.0 percentage of participants |
| Cohort 1: Ociperlimab + Tislelizumab | Clinical Benefit Rate (CBR) | Investigator | 31.2 percentage of participants |
| Cohort 2: Tislelizumab | Clinical Benefit Rate (CBR) | IRC | 50.0 percentage of participants |
| Cohort 2: Tislelizumab | Clinical Benefit Rate (CBR) | Investigator | 50.0 percentage of participants |
Secondary
Cohort 2: Objective Response Rate (ORR) Assessed by an Independent Review Committee in All Treated Participants
ORR is defined as the percentage of participants who had confirmed complete response (CR) or partial response (PR) as assessed by the IRC per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1).
Time frame: Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up duration was 10.40 months for Cohort 2.
Population: The Safety Analysis Set includes all participants who received at least 1 dose of any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Ociperlimab + Tislelizumab | Cohort 2: Objective Response Rate (ORR) Assessed by an Independent Review Committee in All Treated Participants | 32.5 percentage of participants |
Secondary
Disease Control Rate (DCR)
DCR is defined as the percentage of participants who achieve CR, PR, or stable disease (SD) as assessed by both the IRC and investigator per RECIST v1.1 in the Safety Analysis Set.
Time frame: Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up duration was 7.36 months for Cohort 1 and 10.40 months for Cohort 2.
Population: The Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Ociperlimab + Tislelizumab | Disease Control Rate (DCR) | IRC | 63.0 percentage of participants |
| Cohort 1: Ociperlimab + Tislelizumab | Disease Control Rate (DCR) | Investigator | 62.3 percentage of participants |
| Cohort 2: Tislelizumab | Disease Control Rate (DCR) | IRC | 67.5 percentage of participants |
| Cohort 2: Tislelizumab | Disease Control Rate (DCR) | Investigator | 75.0 percentage of participants |
Secondary
Duration of Response (DOR) Assessed by the Investigator
DOR is defined as the time from the first confirmed objective response until the first documentation of progression or death, whichever comes first, assessed by the investigator according to RECIST v1.1 in the Safety Analysis Set. Data was based on number of responders.
Time frame: Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up duration was 7.36 months for Cohort 1 and 10.40 months for Cohort 2.
Population: Safety Analysis Set. Only participants with best overall response of complete response or partial response confirmed per RECIST v1.1 by the investigator were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Ociperlimab + Tislelizumab | Duration of Response (DOR) Assessed by the Investigator | NA Months |
| Cohort 2: Tislelizumab | Duration of Response (DOR) Assessed by the Investigator | NA Months |
Secondary
Duration of Response (DOR) Assessed by the IRC
DOR is defined as the time from the first confirmed objective response until the first documentation of progression or death, whichever occurred first, assessed by the IRC according to RECIST v1.1 in the Safety Analysis Set.
Time frame: Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up duration was 7.36 months for Cohort 1 and 10.40 months for Cohort 2.
Population: Safety Analysis Set. Only participants with best overall response of complete response or partial response confirmed per RECIST v1.1 by the IRC were included in the analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Ociperlimab + Tislelizumab | Duration of Response (DOR) Assessed by the IRC | NA Months |
| Cohort 2: Tislelizumab | Duration of Response (DOR) Assessed by the IRC | NA Months |
Secondary
Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life, Physical Functioning, and Pain 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. Lower scores in symptom scales indicate better quality of life.
Time frame: Baseline to Cycles 3 and 5 ( Each cycle was 21 days)
Population: The Safety Analysis Set with available EORTC QLQ-C30 values at Baseline; Only participants with data at baseline and at each time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Ociperlimab + Tislelizumab | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life, Physical Functioning, and Pain Scores | GHS/QoL: Change from Baseline to Cycle 3 Day 1 | 0.37 Score on a scale | Standard Deviation 22.158 |
| Cohort 1: Ociperlimab + Tislelizumab | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life, Physical Functioning, and Pain Scores | Physical Functioning: Change from Baseline at Cycle 5 Day 1 | 0.00 Score on a scale | Standard Deviation 14.927 |
| Cohort 1: Ociperlimab + Tislelizumab | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life, Physical Functioning, and Pain Scores | Physical Functioning: Baseline Score | 78.91 Score on a scale | Standard Deviation 19.211 |
| Cohort 1: Ociperlimab + Tislelizumab | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life, Physical Functioning, and Pain Scores | Pain: Baseline Score | 27.73 Score on a scale | Standard Deviation 28.07 |
| Cohort 1: Ociperlimab + Tislelizumab | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life, Physical Functioning, and Pain Scores | GHS/QoL: Change from Baseline to Cycle 5 Day 1 | 3.46 Score on a scale | Standard Deviation 18.355 |
| Cohort 1: Ociperlimab + Tislelizumab | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life, Physical Functioning, and Pain Scores | Pain: Change from Baseline at Cycle 3 Day 1 | -2.08 Score on a scale | Standard Deviation 21.82 |
| Cohort 1: Ociperlimab + Tislelizumab | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life, Physical Functioning, and Pain Scores | Physical Functioning: Change from Baseline at Cycle 3 Day 1 | -2.62 Score on a scale | Standard Deviation 16.582 |
| Cohort 1: Ociperlimab + Tislelizumab | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life, Physical Functioning, and Pain Scores | Pain: Change from Baseline at Cycle 5 Day 1 | -2.16 Score on a scale | Standard Deviation 22.353 |
| Cohort 1: Ociperlimab + Tislelizumab | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life, Physical Functioning, and Pain Scores | GHS/QoL: Baseline Score | 64.21 Score on a scale | Standard Deviation 20.821 |
| Cohort 2: Tislelizumab | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life, Physical Functioning, and Pain Scores | Pain: Change from Baseline at Cycle 5 Day 1 | -8.97 Score on a scale | Standard Deviation 24.599 |
| Cohort 2: Tislelizumab | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life, Physical Functioning, and Pain Scores | GHS/QoL: Baseline Score | 62.06 Score on a scale | Standard Deviation 22.402 |
| Cohort 2: Tislelizumab | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life, Physical Functioning, and Pain Scores | GHS/QoL: Change from Baseline to Cycle 3 Day 1 | 5.30 Score on a scale | Standard Deviation 23.088 |
| Cohort 2: Tislelizumab | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life, Physical Functioning, and Pain Scores | GHS/QoL: Change from Baseline to Cycle 5 Day 1 | 5.13 Score on a scale | Standard Deviation 21.995 |
| Cohort 2: Tislelizumab | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life, Physical Functioning, and Pain Scores | Physical Functioning: Baseline Score | 76.67 Score on a scale | Standard Deviation 22.501 |
| Cohort 2: Tislelizumab | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life, Physical Functioning, and Pain Scores | Physical Functioning: Change from Baseline at Cycle 3 Day 1 | 1.82 Score on a scale | Standard Deviation 18.876 |
| Cohort 2: Tislelizumab | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life, Physical Functioning, and Pain Scores | Physical Functioning: Change from Baseline at Cycle 5 Day 1 | 5.38 Score on a scale | Standard Deviation 16.113 |
| Cohort 2: Tislelizumab | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life, Physical Functioning, and Pain Scores | Pain: Baseline Score | 30.26 Score on a scale | Standard Deviation 27.084 |
| Cohort 2: Tislelizumab | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life, Physical Functioning, and Pain Scores | Pain: Change from Baseline at Cycle 3 Day 1 | -9.09 Score on a scale | Standard Deviation 26.051 |
Secondary
Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Symptom Specific Scale for Cervical Cancer (EORTC QLQ-CX24) Index Score
QLQ-CX24 is the cervical cancer module of the QLQ-C30. CX24 is comprised of 24 questions grouped into 3 symptom scales and 6 single symptom items. Each question is answered on a scale from 1 (not at all) to 4 (very much). The scales include Symptom Experience (11 items), Body Image (3 items) and Sexual/vaginal Functioning (4 items). The single symptom items include Lymphedema, Peripheral Neuropathy, Menopausal Symptoms, Sexual Worry, Sexual Activity and Sexual Enjoyment. Raw scores are transformed into a 0 to 100 scale via linear transformation. The Index score is calculated as the average of the 3 symptom scales and 6 single item scores. Lower scores indicate better HRQoL.
Time frame: Baseline to Cycles 3 and 5 ( Each cycle was 21 days)
Population: The Safety Analysis Set with available EORTC QLQ-CX24 values at Baseline; Only participants with data at baseline and at each time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Ociperlimab + Tislelizumab | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Symptom Specific Scale for Cervical Cancer (EORTC QLQ-CX24) Index Score | Baseline Score | 30.86 score on a scale | Standard Deviation 6.942 |
| Cohort 1: Ociperlimab + Tislelizumab | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Symptom Specific Scale for Cervical Cancer (EORTC QLQ-CX24) Index Score | Change from Baseline at Cycle 3 Day 1 | 0.61 score on a scale | Standard Deviation 5.915 |
| Cohort 1: Ociperlimab + Tislelizumab | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Symptom Specific Scale for Cervical Cancer (EORTC QLQ-CX24) Index Score | Change from Baseline at Cycle 5 Day 1 | -0.15 score on a scale | Standard Deviation 5.79 |
| Cohort 2: Tislelizumab | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Symptom Specific Scale for Cervical Cancer (EORTC QLQ-CX24) Index Score | Baseline Score | 31.43 score on a scale | Standard Deviation 4.497 |
| Cohort 2: Tislelizumab | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Symptom Specific Scale for Cervical Cancer (EORTC QLQ-CX24) Index Score | Change from Baseline at Cycle 3 Day 1 | -0.71 score on a scale | Standard Deviation 4.163 |
| Cohort 2: Tislelizumab | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Symptom Specific Scale for Cervical Cancer (EORTC QLQ-CX24) Index Score | Change from Baseline at Cycle 5 Day 1 | 1.05 score on a scale | Standard Deviation 4.227 |
Secondary
Number of Participants Experiencing Treatment-emergent Adverse Events (AEs) 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 considered 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 (eg, may jeopardize the patient or may require medical/surgical intervention to prevent one of the outcomes listed above).
Time frame: From the first dose of study drug to 30 days after the last dose; maximum treatment exposure was 23.5 months.
Population: The Safety Analysis Set includes all participants who received at least 1 dose of any study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Ociperlimab + Tislelizumab | Number of Participants Experiencing Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of Participants with at least one TEAE | 135 Participants |
| Cohort 1: Ociperlimab + Tislelizumab | Number of Participants Experiencing Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with at least one SAE | 61 Participants |
| Cohort 2: Tislelizumab | Number of Participants Experiencing Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of Participants with at least one TEAE | 39 Participants |
| Cohort 2: Tislelizumab | Number of Participants Experiencing Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with at least one SAE | 17 Participants |
Secondary
Number of Participants Who Developed Anti-drug Antibodies (ADAs) to Tislelizumab
Number and percentage of participants who developed detectable ADAs during the treatment period.
Time frame: Samples for ADA analysis were collected predose on Day 1 of Cycles 1, 2, 5, 9 and 17, and at the Safety Follow-up Visit (30 days after last dose), up to the immunogenicity data cut-off date of June 1, 2023 (approximately 21 months).
Population: The ADA Analysis Set includes all participants who received at least 1 dose of any component of study drug for whom both baseline antidrug antibody result and at least 1 post-baseline antidrug antibody result are available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Ociperlimab + Tislelizumab | Number of Participants Who Developed Anti-drug Antibodies (ADAs) to Tislelizumab | 19 Participants |
| Cohort 2: Tislelizumab | Number of Participants Who Developed Anti-drug Antibodies (ADAs) to Tislelizumab | 7 Participants |
Secondary
Number of Participants Who Developed Positive Anti-drug Antibodies (ADAs) to Ociperlimab
Number and percentage of participants who developed detectable ADAs to ociperlimab during the treatment period.
Time frame: Samples for ADA analysis were collected predose on Day 1 of Cycles 1, 2, 5, 9 and 17, and at the Safety Follow-up Visit (30 days after last dose) up to the immunogenicity data cut-off date of June 1, 2023 (approximately 21 months).
Population: The ADA Analysis Set includes all participants who received at least 1 dose of any component of study drug for whom both baseline antidrug antibody result and at least 1 post-baseline antidrug antibody result were available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Ociperlimab + Tislelizumab | Number of Participants Who Developed Positive Anti-drug Antibodies (ADAs) to Ociperlimab | 0 Participants |
Secondary
ORR as Assessed by the Investigator in All Treated Participants
ORR is defined as the percentage of participants who had a confirmed CR or PR as assessed by the investigator per RECIST v1.1.
Time frame: Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up duration was 7.36 months for Cohort 1 and 10.40 months for Cohort 2.
Population: The Safety Analysis Set includes participants who received at least 1 dose of any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Ociperlimab + Tislelizumab | ORR as Assessed by the Investigator in All Treated Participants | 21.0 percentage of participants |
| Cohort 2: Tislelizumab | ORR as Assessed by the Investigator in All Treated Participants | 22.5 percentage of participants |
Secondary
ORR Assessed by the Investigator in PD-L1-Positive Participants
ORR is defined as the percentage of participants who had confirmed CR or PR as assessed by the investigator per RECIST v1.1 in the PD-L1 Score \>= 5% Safety Analysis Set.
Time frame: Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up duration was 7.36 months for Cohort 1 and 10.40 months for Cohort 2.
Population: The PD-L1 Score ≥ 5% Safety Analysis Set includes all treated participants whose tumors had PD-L1 Score ≥ 5%.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Ociperlimab + Tislelizumab | ORR Assessed by the Investigator in PD-L1-Positive Participants | 25.0 percentage of participants |
| Cohort 2: Tislelizumab | ORR Assessed by the Investigator in PD-L1-Positive Participants | 30 percentage of participants |
Secondary
Overall Survival (OS)
Overall survival is defined as the time from the date of randomization to the date of death due to any cause. Median OS was estimated using Kaplan-Meier methodology.
Time frame: Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up duration was 7.36 months for Cohort 1 and 10.40 months for Cohort 2.
Population: The Safety Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Ociperlimab + Tislelizumab | Overall Survival (OS) | 9.0 Months |
| Cohort 2: Tislelizumab | Overall Survival (OS) | NA Months |
Secondary
Progression Free Survival (PFS)
Defined as the time from the date of first dose of study drug to the date of first documentation of disease progression or death, whichever occurred first as assessed by both the IRC and the investigator's review per RECIST v1.1 in the Safety Analysis Set.
Time frame: Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up duration was 7.36 months for Cohort 1 and 10.40 months for Cohort 2.
Population: Safety Analysis Set
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: Ociperlimab + Tislelizumab | Progression Free Survival (PFS) | IRC | 3.5 Months |
| Cohort 1: Ociperlimab + Tislelizumab | Progression Free Survival (PFS) | Investigator | 3.9 Months |
| Cohort 2: Tislelizumab | Progression Free Survival (PFS) | IRC | 5.7 Months |
| Cohort 2: Tislelizumab | Progression Free Survival (PFS) | Investigator | 5.7 Months |
Secondary
Serum Ociperlimab (BGB-A1217) Concentrations at Specified Timepoints
The timepoints are defined as predose (within 60 minutes before starting infusion) and postdose (within 30 minutes after the end of infusion).
Time frame: Day 1 of Cycles 1, 2, 5, 9, and 17 (each cycle was 21 days)
Population: The Pharmacokinetic Analysis (PK) Set includes all participants who received at least 1 dose of any component of study drug per the protocol, for whom any post-dose PK data are available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Ociperlimab + Tislelizumab | Serum Ociperlimab (BGB-A1217) Concentrations at Specified Timepoints | Cycle 5 Day 1 | 82.57 μg/mL | Geometric Coefficient of Variation 55.3 |
| Cohort 1: Ociperlimab + Tislelizumab | Serum Ociperlimab (BGB-A1217) Concentrations at Specified Timepoints | Cycle 9 Day 1 | 89.13 μg/mL | Geometric Coefficient of Variation 56.58 |
| Cohort 1: Ociperlimab + Tislelizumab | Serum Ociperlimab (BGB-A1217) Concentrations at Specified Timepoints | Cycle 17 Day 1 | 88.84 μg/mL | Geometric Coefficient of Variation 63.62 |
| Cohort 1: Ociperlimab + Tislelizumab | Serum Ociperlimab (BGB-A1217) Concentrations at Specified Timepoints | Cycle 2 Day 1 | 46.60 μg/mL | Geometric Coefficient of Variation 46.98 |
| Cohort 1: Ociperlimab + Tislelizumab | Serum Ociperlimab (BGB-A1217) Concentrations at Specified Timepoints | Cycle 1 Day 1 | 0.00 μg/mL | — |
| Cohort 2: Tislelizumab | Serum Ociperlimab (BGB-A1217) Concentrations at Specified Timepoints | Cycle 1 Day 1 | 363.19 μg/mL | Geometric Coefficient of Variation 24.21 |
| Cohort 2: Tislelizumab | Serum Ociperlimab (BGB-A1217) Concentrations at Specified Timepoints | Cycle 5 Day 1 | 440.70 μg/mL | Geometric Coefficient of Variation 25.35 |
Secondary
Serum Tislelizumab Concentrations at Specified Timepoints
The timepoints are defined as predose (within 60 minutes before starting infusion) and postdose (within 30 minutes after the end of infusion).
Time frame: Day 1 of Cycles 1, 2, 5, 9, and 17 (each cycle is 21 days)
Population: The Pharmacokinetic Analysis Set includes all participants who received \>= 1 dose of any component of study drug per the protocol, for whom any post-dose PK data are available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Ociperlimab + Tislelizumab | Serum Tislelizumab Concentrations at Specified Timepoints | Cycle 1 Day 1 | 0.00 μg/mL | — |
| Cohort 1: Ociperlimab + Tislelizumab | Serum Tislelizumab Concentrations at Specified Timepoints | Cycle 5 Day 1 | 36.66 μg/mL | Geometric Coefficient of Variation 44.97 |
| Cohort 1: Ociperlimab + Tislelizumab | Serum Tislelizumab Concentrations at Specified Timepoints | Cycle 17 Day 1 | 45.16 μg/mL | Geometric Coefficient of Variation 55.71 |
| Cohort 1: Ociperlimab + Tislelizumab | Serum Tislelizumab Concentrations at Specified Timepoints | Cycle 9 Day 1 | 42.84 μg/mL | Geometric Coefficient of Variation 46.5 |
| Cohort 1: Ociperlimab + Tislelizumab | Serum Tislelizumab Concentrations at Specified Timepoints | Cycle 2 Day 1 | 17.86 μg/mL | Geometric Coefficient of Variation 35.69 |
| Cohort 2: Tislelizumab | Serum Tislelizumab Concentrations at Specified Timepoints | Cycle 5 Day 1 | 113.80 μg/mL | Geometric Coefficient of Variation 24.68 |
| Cohort 2: Tislelizumab | Serum Tislelizumab Concentrations at Specified Timepoints | Cycle 1 Day 1 | 77.38 μg/mL | Geometric Coefficient of Variation 21.78 |
| Cohort 2 (Predose) | Serum Tislelizumab Concentrations at Specified Timepoints | Cycle 1 Day 1 | 0.00 μg/mL | — |
| Cohort 2 (Predose) | Serum Tislelizumab Concentrations at Specified Timepoints | Cycle 17 Day 1 | 56.25 μg/mL | Geometric Coefficient of Variation 21.56 |
| Cohort 2 (Predose) | Serum Tislelizumab Concentrations at Specified Timepoints | Cycle 5 Day 1 | 41.51 μg/mL | Geometric Coefficient of Variation 42.89 |
| Cohort 2 (Predose) | Serum Tislelizumab Concentrations at Specified Timepoints | Cycle 2 Day 1 | 20.03 μg/mL | Geometric Coefficient of Variation 36.62 |
| Cohort 2 (Predose) | Serum Tislelizumab Concentrations at Specified Timepoints | Cycle 9 Day 1 | 56.78 μg/mL | Geometric Coefficient of Variation 28.55 |
| Cohort 2 (Postdose) | Serum Tislelizumab Concentrations at Specified Timepoints | Cycle 1 Day 1 | 84.24 μg/mL | Geometric Coefficient of Variation 18.19 |
| Cohort 2 (Postdose) | Serum Tislelizumab Concentrations at Specified Timepoints | Cycle 5 Day 1 | 128.48 μg/mL | Geometric Coefficient of Variation 24.06 |
Secondary
Time to Response (TTR) Assessed by the Investigator
TTR is defined as the time from the date of first dose of study drug to the first documentation of response as assessed by the investigator per RECIST v1.1, in the Safety Analysis Set.
Time frame: Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up was 7.36 months for Cohort 1 and 10.40 months for Cohort 2.
Population: The Safety Analysis Set. Only participants with best overall response of complete response or partial response confirmed by the investigator per RECIST v1.1 were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Ociperlimab + Tislelizumab | Time to Response (TTR) Assessed by the Investigator | 10.66 Weeks | Standard Deviation 3.01 |
| Cohort 2: Tislelizumab | Time to Response (TTR) Assessed by the Investigator | 8.92 Weeks | Standard Deviation 3.174 |
Secondary
Time to Response (TTR) Assessed by the IRC
TTR is defined as the time from the date of first dose of study drug to the first documentation of response as assessed by the IRC per RECIST v1.1, in the Safety Analysis Set.
Time frame: Up to the primary efficacy analysis data cut-off date on June 16, 2022, the median follow-up was 7.36 months for Cohort 1 and 10.40 months for Cohort 2.
Population: The Safety Analysis Set. Only participants with best overall response of complete response or partial response confirmed by the IRC per RECIST v1.1 were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Ociperlimab + Tislelizumab | Time to Response (TTR) Assessed by the IRC | 9.02 Weeks | Standard Deviation 4.704 |
| Cohort 2: Tislelizumab | Time to Response (TTR) Assessed by the IRC | 11.78 Weeks | Standard Deviation 4.709 |