Non Small Cell Lung Cancer
Conditions
Brief summary
The purpose of this study was to evaluate the safety and efficacy of ociperlimab in combination with tislelizumab compared to durvalumab in adults with stage III unresectable PD-L1-selected non-small cell lung cancer whose disease has not progressed after cCRT.
Detailed description
The study initiated with Protocol Amendment 1.0 (PA 1; dated on 16 April 2021). In April 2022 Protocol Amendment 2 (PA 2) was implemented. In PA 1, participants with newly diagnosed, histologically confirmed, unresectable locally advanced NSCLC and evaluable PD-L1 expression all comers were enrolled; cCRT was given within the study. In PA 2, the enrollment of the target population was revised into participants with unresectable locally advanced NSCLC whose disease has not progressed after definitive, platinum-based cCRT and with PD-L1 expression on ≥ 1% of tumor cells as assessed by the central lab; cCRT was given outside of the study. After implementation of PA 2, participants who were randomized under PA 1 were given the option to continue assigned study treatment or to discontinue assigned treatment and begin standard of care treatment outside of the study. Participants enrolled under PA 1 were excluded from the primary and secondary analysis specified by PA 2. This study was subsequently terminated by the Sponsor prior to enrollment of any participants under PA 2.
Interventions
DRUGTislelizumab
200 mg intravenously every three weeks
DRUGDurvalumab
10 milligrams per kilogram (mg/kg) intravenously once every 2 weeks (or 1500 mg intravenously once every 4 weeks where the dosage has been approved by a local health authority)
DRUGOciperlimab
900 milligrams (mg) intravenously every three weeks
DRUGChemotherapy
The chemotherapy regimen for the study treatment was selected at the investigator's discretion and may include one of the following options: * Cisplatin (50 mg/m²) on days 1 to 5 of each cycle, combined with etoposide (50 mg/m²) on days 1 and 8, both administered intravenously for 2 cycles. Each cycle was 28 days. * Carboplatin (AUC 2) weekly for 6 weeks, combined with paclitaxel (40-50 mg/m²) weekly for 6 weeks, both administered intravenously. * Cisplatin (75 mg/m²) combined with pemetrexed (500 mg/m²) on day 1 of each cycle, administered intravenously for 2 cycles. Each cycle was 21 days. * Carboplatin (AUC 5) combined with pemetrexed (500 mg/m²) on day 1 of each cycle, administered intravenously for 2 cycles. Each cycle was 21 days. The pemetrexed plus platinum regimen was only for participants with non-squamous histology.
RADIATIONRadiotherapy
All participants recieved radiotherapy using either a standardized 3-dimensional conformal radiotherapy technique, or intensity modulated radiotherapy (IMRT) on a linear accelerator delivering a beam energy of ≥ 6 MV. The total dose of radiotherapy was 60 Gy, administered in 30 once-daily fractions of 2 Gy and 5 fractions per week for 6 weeks.
Sponsors
BeiGene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Age ≥ 18 years on the day of signing the informed consent form (or the legal age of consent in the jurisdiction in which the study is taking place). 2. Participant has histologically or cytologically confirmed, locally advanced, unresectable Stage III NSCLC (AJCC Cancer Staging Manual 2017, derived from IASLC) prior to initiation of cCRT. 3. Participant must have completed at least 2 cycles of platinum-based chemotherapy concurrent with radiotherapy 4. Participants must have not experienced PD following definitive, platinum-based cCRT. 5. Eastern Co-operative Oncology Group (ECOG) Performance Status of 0 or 1. 6. Participants must have adequate organ function 7. Agree to provide archival tissue (formalin-fixed paraffin-embedded block containing tumor \[preferred\] or approximately 6 to 15 freshly cut unstained slides) or fresh biopsy obtained prior to cCRT (if archival tissue is not available) for prospective central evaluation of PD-L1 levels and retrospective analysis of other biomarkers. Key
Exclusion criteria
1. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, TIGIT, or any other antibody or drugs specifically targeting T-cell co-stimulation or checkpoint pathways. 2. Diagnosed with NSCLC that harbors an epidermal growth factor receptor (EGFR) sensitizing mutation, anaplastic lymphoma kinase (ALK) gene translocation, ROS1 gene translocation or RET gene rearrangement. 3. Participants who received systemic anticancer treatment besides the specified cCRT. 4. Any unresolved toxicity CTCAE \> Grade 2 from the prior cCRT. 5. Active autoimmune diseases or history of autoimmune diseases that may relapse. 6. Any condition that required systemic treatment with either corticosteroids (\> 10 mg daily of prednisone \[in Japan, prednisolone\] or equivalent) or other immunosuppressive medication ≤ 14 days before the first dose of study treatment. 7. Infection (including tuberculosis infection, etc) requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days before the first dose of study treatment. Note: Antiviral therapy is permitted for participants with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. NOTE: Other protocol Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) as Assessed by the Independent Review Committee (IRC) | From randomization through to the end of study, planned duration was 20 months | PFS is defined as the time from the date of randomization to the date of first documentation of disease progression as assessed by the IRC per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 or death, whichever occurred first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | From randomization through to the end of study, planned duration was 20 months | Defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) assessed by both the IRC and investigators per RECIST v1.1. |
| Duration of Response (DOR) | From randomization through to the end of study, planned duration was 20 months | defined as the time from the first determination of a confirmed objective response assessed by both the IRC and investigators per RECIST v1.1 until the first documentation of disease progression or death, whichever occurs first |
| Time to Death or Distant Metastasis (TTDM) as Assessed by the Investigator | From randomization through to the end of study, planned duration was 20 months | defined as the time from the date of randomization until the first date of distant metastasis assessed by both the IRC and investigators, or death. Distant metastasis is defined as any new lesion that is outside of the radiation field per RECIST v1.1 or proven by biopsy. |
| Progression-Free Survival 2 (PFS2) | From randomization through to the end of study, planned duration was 20 months | defined as the time from randomization to the disease progression after next line of treatment, or death from any cause, whichever occurs first |
| Number of Participants Experiencing Adverse Events (AEs) | From first dose to 30 days after the last dose or initiation of a new anticancer therapy, whichever occured first; through study completion data cut-off date of October 17th, 2023 (maximum time on treatment was 16 months) | Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) determined according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) |
| Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status | Baseline and Cycle 6 (Each cycle is 21 days) | Change from baseline in EORTC QLQ-C30 Global Health Status/Quality of Life score. The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of participants with cancer. It includes global health status and quality of life questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes. |
| Change From Baseline in Health Related Quality of Life (HRQoL) as Assessed by Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) | Baseline and Cycle 6 (Each cycle is 21 days) | Change from baseline in QLQ-CL13 scores for coughing, dyspnea, and chest pain. The QLQ-LC13 is a questionnaire that measures lung cancer-specific disease and treatment symptoms. It includes 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. A lower score indicates an improvement in symptoms. |
| Overall Survival (OS) | From randomization through to the end of study, planned duration was 20 months | Defined as the time from the date of randomization until the date of death due to any cause |
| Serum Concentration of Ociperlimab | Predose at Day 1 of Cycles 1, 2, 5, 9, and 17; postdose on Day 1 of Cycles 1, 5 and EOT visit (Each Cycle was 21 days) | Serum concentrations of ociperlimab were measured for participants in the Ociperlimab + Tislelizumab + cCRT treatment group at predose (within 60 minutes before starting infusion) and postdose (within 30 minutes after the end of infusion). End of Treatment (EOT) visits occurred within 7 days after the date the investigator determined that study treatment would no longer be used, or before the initiation of a new anticancer treatment, whichever occurred first. |
| Serum Concentration of Tislelizumab for Participants in the Ociperlimab + Tislelizumab + cCRT Treatment Group | Predose at Day 1 of Cycles 1, 2, 5, 9, 17; postdose on Day 1 of Cycles 1 and 5, and EOT visit (each cycle was 21 days) | Serum concentrations of tislelizumab were collected for participants in the Ociperlimab + Tislelizumab + cCRT treatment group at predose (within 60 minutes before starting infusion) and postdose (within 30 minutes after the end of infusion). End of Treatment (EOT) visits occurred within 7 days after the date investigator determined that study treatment would no longer be used, or before the initiation of a new anticancer treatment, whichever occurred first. |
| Serum Concentration of Tislelizumab for Participants in the Tislelizumab + cCRT Treatment Group | Predose at Day 1 of Cycles 1, 2, 5, 9, and 17; postdose on Day 1 of Cycles 1 and 5, and EOT visit (Each Cycle is 21 days) | Serum concentrations of tislelizumab were collected for participants in the Tislelizumab + cCRT treatment group at predose (within 60 minutes prior to infusion initiation) and postdose (within 30 minutes after the completion of infusion). End of Treatment (EOT) visits occurred within 7 days after the date investigator determined that study treatment would no longer be used, or before the initiation of a new anticancer treatment, whichever occurred first. |
| Immunogenic Responses to Ociperlimab as Assessed by the Detection of Treatment Emergent Anti-Drug Antibodies (ADAs) | Predose (within 60 minutes before dose) on Day 1 of Cycles 1, 2, 5, 9, 17, and the EOT Visit (Each cycle is 21 days). Maximum number of treatment cycles was 19 | Defined as the sum of treatment-boosted and treatment-induced ADA participants as a proportion percentage of the ADA-evaluable participants population and is synonymous with 'ADA Incidence'. ADA samples were collected for participants randomized to Arm A (ociperlimab and tislelizumab) |
| Immunogenic Responses to Tislelizumab as Assessed by the Detection of Treatment Emergent Anti-Drug Antibodies (ADAs) | Predose (within 60 minutes before dose) on Day 1 of Cycles 1, 2, 5, 9, 17, and the EOT Visit (Each cycle is 21 days, maximum number of treatment cycles was 19) | Defined as the sum of treatment-boosted and treatment-induced ADA participants as a proportion percentage of the ADA-evaluable participants population and is synonymous with 'ADA Incidence'. ADA samples were collected for participants randomized to Arm A (Ociperlimab + Tislelizumab + cCRT) and Arm B (Tislelizumab + cCRT) |
| Programmed Death-Ligand 1 (PD-L1) and T-cell Immunoreceptor With Ig and ITIM Domains (TIGIT) Expression in Archival and/or Fresh Tumor Tissues | From randomization through to the end of study, planned duration was 20 months | — |
| Change From Baseline in Health Related Quality of Life (HRQoL) as Assessed by European Quality of Life-5 Dimensions (EQ-5D-5L) | Baseline and Cycle 6 (Each cycle is 21 days) | The EuroQol 5D-5L a descriptive system that comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The participant is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the participant's health state. |
Countries
Australia, China, Spain, Taiwan, United States
Participant flow
Recruitment details
Participants were enrolled in multiple study centers in Taiwan, China, Spain , United States, and Australia. The first participant was consented on June 17th, 2021, and the last participant completed on October 17th, 2023. The decision to terminate the study was made on July 11th, 2023.
Pre-assignment details
This study was initiated under Protocol Amendment (PA) 1. PA 2 was subsequently implemented; however, no participants were enrolled under PA 2 before the study was terminated. PA 2 changed the eligibility criteria, study treatment, study objectives and endpoints and excluded participants enrolled under PA 1 from analysis of the primary and secondary efficacy endpoint analyses.
Participants by arm
| Arm | Count |
|---|---|
| Ociperlimab + Tislelizumab + cCRT Participants enrolled in PA 1 received two cycles of ociperlimab (900 mg) and tislelizumab (200 mg) intravenously every three weeks, combined with concurrent chemoradiotherapy (cCRT). Chemotherapy regimens varied based on investigator discretion, including options such as cisplatin with etoposide, carboplatin with paclitaxel, or platinum-based regimens with pemetrexed for non-squamous histology; alongside radiotherapy. After the cCRT phase, participants continued ociperlimab and tislelizumab treatment for up to one year. | 22 |
| Tislelizumab + cCRT Participants in PA 1 received two cycles of tislelizumab (200 mg) intravenously every three weeks, combined with concurrent chemoradiotherapy (cCRT). The chemotherapy regimen was determined by the investigator and included options like cisplatin with etoposide, carboplatin with paclitaxel, or platinum-based regimens with pemetrexed for non-squamous histology; alongside radiotherapy. Following the cCRT phase, participants continued tislelizumab treatment for up to one year. | 19 |
| cCRT Followed by Durvalumab Participants in PA 1 received two cycles of concurrent chemoradiotherapy (cCRT), followed by durvalumab (10 mg/kg intravenously every 2 weeks, or 1500 mg every 4 weeks if locally approved). The chemotherapy regimen was chosen by the investigator and included options such as cisplatin with etoposide, carboplatin with paclitaxel, or pemetrexed with a platinum agent for non-squamous histology; alongside radiotherapy. After cCRT, participants continued durvalumab treatment for up to one year. | 22 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 8 | 4 | 8 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Study Terminated by Sponsor | 13 | 14 | 13 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Ociperlimab + Tislelizumab + cCRT | Tislelizumab + cCRT | cCRT Followed by Durvalumab | Total |
|---|---|---|---|---|
| Age, Continuous | 63.4 years STANDARD_DEVIATION 7.51 | 62.4 years STANDARD_DEVIATION 9.27 | 64.1 years STANDARD_DEVIATION 7.36 | 63.3 years STANDARD_DEVIATION 7.93 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 18 Participants | 15 Participants | 18 Participants | 51 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 4 Participants | 4 Participants | 12 Participants |
| Region of Enrollment Australia | 1 participants | 2 participants | 0 participants | 3 participants |
| Region of Enrollment China | 17 participants | 12 participants | 16 participants | 45 participants |
| Region of Enrollment Spain | 1 participants | 1 participants | 3 participants | 5 participants |
| Region of Enrollment Taiwan | 1 participants | 3 participants | 2 participants | 6 participants |
| Region of Enrollment United States | 2 participants | 1 participants | 1 participants | 4 participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 0 Participants | 8 Participants |
| Sex: Female, Male Male | 19 Participants | 14 Participants | 22 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 8 / 22 | 4 / 18 | 8 / 22 |
| other Total, other adverse events | 22 / 22 | 18 / 18 | 22 / 22 |
| serious Total, serious adverse events | 11 / 22 | 8 / 18 | 8 / 22 |
Outcome results
Primary
Progression-Free Survival (PFS) as Assessed by the Independent Review Committee (IRC)
PFS is defined as the time from the date of randomization to the date of first documentation of disease progression as assessed by the IRC per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 or death, whichever occurred first.
Time frame: From randomization through to the end of study, planned duration was 20 months
Population: The primary endpoint was specified in PA 2 and excludes participants enrolled under PA 1. No participants were enrolled under PA 2.
Secondary
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status
Change from baseline in EORTC QLQ-C30 Global Health Status/Quality of Life score. The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of participants with cancer. It includes global health status and quality of life questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes.
Time frame: Baseline and Cycle 6 (Each cycle is 21 days)
Population: This secondary endpoint was specified in PA 2 and excludes participants enrolled under PA 1. No participants were enrolled under PA 2.
Secondary
Change From Baseline in Health Related Quality of Life (HRQoL) as Assessed by European Quality of Life-5 Dimensions (EQ-5D-5L)
The EuroQol 5D-5L a descriptive system that comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The participant is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the participant's health state.
Time frame: Baseline and Cycle 6 (Each cycle is 21 days)
Population: This secondary endpoint was specified in PA 2 and excludes participants enrolled under PA 1. No participants were enrolled under PA 2.
Secondary
Change From Baseline in Health Related Quality of Life (HRQoL) as Assessed by Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13)
Change from baseline in QLQ-CL13 scores for coughing, dyspnea, and chest pain. The QLQ-LC13 is a questionnaire that measures lung cancer-specific disease and treatment symptoms. It includes 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. A lower score indicates an improvement in symptoms.
Time frame: Baseline and Cycle 6 (Each cycle is 21 days)
Population: This secondary endpoint was specified in PA 2 and excludes participants enrolled under PA 1. No participants were enrolled under PA 2.
Secondary
Duration of Response (DOR)
defined as the time from the first determination of a confirmed objective response assessed by both the IRC and investigators per RECIST v1.1 until the first documentation of disease progression or death, whichever occurs first
Time frame: From randomization through to the end of study, planned duration was 20 months
Population: This secondary endpoint was specified in PA 2 and excludes participants enrolled under PA 1. No participants were enrolled under PA 2.
Secondary
Immunogenic Responses to Ociperlimab as Assessed by the Detection of Treatment Emergent Anti-Drug Antibodies (ADAs)
Defined as the sum of treatment-boosted and treatment-induced ADA participants as a proportion percentage of the ADA-evaluable participants population and is synonymous with 'ADA Incidence'. ADA samples were collected for participants randomized to Arm A (ociperlimab and tislelizumab)
Time frame: Predose (within 60 minutes before dose) on Day 1 of Cycles 1, 2, 5, 9, 17, and the EOT Visit (Each cycle is 21 days). Maximum number of treatment cycles was 19
Population: The Immunogenicity Analysis Set includes all participants who received any dose of any component of study drugs and for whom both baseline antidrug antibody (ADA) and at least 1 postbaseline ADA result were available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ociperlimab + Tislelizumab + cCRT | Immunogenic Responses to Ociperlimab as Assessed by the Detection of Treatment Emergent Anti-Drug Antibodies (ADAs) | 0 Participants |
Secondary
Immunogenic Responses to Tislelizumab as Assessed by the Detection of Treatment Emergent Anti-Drug Antibodies (ADAs)
Defined as the sum of treatment-boosted and treatment-induced ADA participants as a proportion percentage of the ADA-evaluable participants population and is synonymous with 'ADA Incidence'. ADA samples were collected for participants randomized to Arm A (Ociperlimab + Tislelizumab + cCRT) and Arm B (Tislelizumab + cCRT)
Time frame: Predose (within 60 minutes before dose) on Day 1 of Cycles 1, 2, 5, 9, 17, and the EOT Visit (Each cycle is 21 days, maximum number of treatment cycles was 19)
Population: The Immunogenicity Analysis Set includes all participants who received any dose of any component of study drugs and for whom both baseline antidrug antibody (ADA) and at least 1 postbaseline ADA result were available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ociperlimab + Tislelizumab + cCRT | Immunogenic Responses to Tislelizumab as Assessed by the Detection of Treatment Emergent Anti-Drug Antibodies (ADAs) | 10 Participants |
| Tislelizumab + cCRT | Immunogenic Responses to Tislelizumab as Assessed by the Detection of Treatment Emergent Anti-Drug Antibodies (ADAs) | 5 Participants |
Secondary
Number of Participants Experiencing Adverse Events (AEs)
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) determined according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0)
Time frame: From first dose to 30 days after the last dose or initiation of a new anticancer therapy, whichever occured first; through study completion data cut-off date of October 17th, 2023 (maximum time on treatment was 16 months)
Population: The Safety Analysis Set included all randomized patients who received any dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ociperlimab + Tislelizumab + cCRT | Number of Participants Experiencing Adverse Events (AEs) | TEAEs | 22 Participants |
| Ociperlimab + Tislelizumab + cCRT | Number of Participants Experiencing Adverse Events (AEs) | SAEs | 11 Participants |
| Tislelizumab + cCRT | Number of Participants Experiencing Adverse Events (AEs) | TEAEs | 18 Participants |
| Tislelizumab + cCRT | Number of Participants Experiencing Adverse Events (AEs) | SAEs | 8 Participants |
| cCRT Followed by Durvalumab | Number of Participants Experiencing Adverse Events (AEs) | TEAEs | 22 Participants |
| cCRT Followed by Durvalumab | Number of Participants Experiencing Adverse Events (AEs) | SAEs | 8 Participants |
Secondary
Overall Response Rate (ORR)
Defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) assessed by both the IRC and investigators per RECIST v1.1.
Time frame: From randomization through to the end of study, planned duration was 20 months
Population: This secondary endpoint was specified in PA 2 and excludes participants enrolled under PA 1. No participants were enrolled under PA 2.
Secondary
Overall Survival (OS)
Defined as the time from the date of randomization until the date of death due to any cause
Time frame: From randomization through to the end of study, planned duration was 20 months
Population: This secondary endpoint was specified in PA 2 and excludes participants enrolled under PA 1. No participants were enrolled under PA 2.
Secondary
Programmed Death-Ligand 1 (PD-L1) and T-cell Immunoreceptor With Ig and ITIM Domains (TIGIT) Expression in Archival and/or Fresh Tumor Tissues
Time frame: From randomization through to the end of study, planned duration was 20 months
Population: This secondary endpoint was specified in PA 2 and excludes participants enrolled under PA 1. No participants were enrolled under PA 2.
Secondary
Progression-Free Survival 2 (PFS2)
defined as the time from randomization to the disease progression after next line of treatment, or death from any cause, whichever occurs first
Time frame: From randomization through to the end of study, planned duration was 20 months
Population: This secondary endpoint was specified in PA 2 and excludes participants enrolled under PA 1. No participants were enrolled under PA 2.
Secondary
Serum Concentration of Ociperlimab
Serum concentrations of ociperlimab were measured for participants in the Ociperlimab + Tislelizumab + cCRT treatment group at predose (within 60 minutes before starting infusion) and postdose (within 30 minutes after the end of infusion). End of Treatment (EOT) visits occurred within 7 days after the date the investigator determined that study treatment would no longer be used, or before the initiation of a new anticancer treatment, whichever occurred first.
Time frame: Predose at Day 1 of Cycles 1, 2, 5, 9, and 17; postdose on Day 1 of Cycles 1, 5 and EOT visit (Each Cycle was 21 days)
Population: The Pharmacokinetics (PK) Analysis Set includes all patients who receive any dose of any component of study drugs and for whom any postdose PK data are available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ociperlimab + Tislelizumab + cCRT | Serum Concentration of Ociperlimab | Cycle 9 Day 1 | 52.4 ug/ml | Geometric Coefficient of Variation 82.4 |
| Ociperlimab + Tislelizumab + cCRT | Serum Concentration of Ociperlimab | Cycle 17 Day 1 | 81.35 ug/ml | Geometric Coefficient of Variation 53.83 |
| Ociperlimab + Tislelizumab + cCRT | Serum Concentration of Ociperlimab | Cycle 1 Day 1 | 18 ug/ml | — |
| Ociperlimab + Tislelizumab + cCRT | Serum Concentration of Ociperlimab | Cycle 5 Day 1 | 74.86 ug/ml | Geometric Coefficient of Variation 61.76 |
| Ociperlimab + Tislelizumab + cCRT | Serum Concentration of Ociperlimab | Cycle 2 Day 1 | 34.54 ug/ml | Geometric Coefficient of Variation 63.19 |
| Tislelizumab + cCRT | Serum Concentration of Ociperlimab | End of Treatment | 94.94 ug/ml | Geometric Coefficient of Variation 232.05 |
| Tislelizumab + cCRT | Serum Concentration of Ociperlimab | Cycle 1 Day 1 | 312 ug/ml | Geometric Coefficient of Variation 45.82 |
| Tislelizumab + cCRT | Serum Concentration of Ociperlimab | Cycle 5 Day 1 | 339.31 ug/ml | Geometric Coefficient of Variation 38.21 |
Secondary
Serum Concentration of Tislelizumab for Participants in the Ociperlimab + Tislelizumab + cCRT Treatment Group
Serum concentrations of tislelizumab were collected for participants in the Ociperlimab + Tislelizumab + cCRT treatment group at predose (within 60 minutes before starting infusion) and postdose (within 30 minutes after the end of infusion). End of Treatment (EOT) visits occurred within 7 days after the date investigator determined that study treatment would no longer be used, or before the initiation of a new anticancer treatment, whichever occurred first.
Time frame: Predose at Day 1 of Cycles 1, 2, 5, 9, 17; postdose on Day 1 of Cycles 1 and 5, and EOT visit (each cycle was 21 days)
Population: PK Analysis Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ociperlimab + Tislelizumab + cCRT | Serum Concentration of Tislelizumab for Participants in the Ociperlimab + Tislelizumab + cCRT Treatment Group | Cycle 9 Day 1 | 30.22 ug/mL | Geometric Coefficient of Variation 55.34 |
| Ociperlimab + Tislelizumab + cCRT | Serum Concentration of Tislelizumab for Participants in the Ociperlimab + Tislelizumab + cCRT Treatment Group | Cycle 17 Day 1 | 32.24 ug/mL | Geometric Coefficient of Variation 156.53 |
| Ociperlimab + Tislelizumab + cCRT | Serum Concentration of Tislelizumab for Participants in the Ociperlimab + Tislelizumab + cCRT Treatment Group | Cycle 1 Day 1 | NA ug/mL | — |
| Ociperlimab + Tislelizumab + cCRT | Serum Concentration of Tislelizumab for Participants in the Ociperlimab + Tislelizumab + cCRT Treatment Group | Cycle 5 Day 1 | 34.10 ug/mL | Geometric Coefficient of Variation 49.67 |
| Ociperlimab + Tislelizumab + cCRT | Serum Concentration of Tislelizumab for Participants in the Ociperlimab + Tislelizumab + cCRT Treatment Group | Cycle 2 Day 1 | 15.91 ug/mL | Geometric Coefficient of Variation 78.83 |
| Tislelizumab + cCRT | Serum Concentration of Tislelizumab for Participants in the Ociperlimab + Tislelizumab + cCRT Treatment Group | End of Treatment | 49.55 ug/mL | Geometric Coefficient of Variation 89.19 |
| Tislelizumab + cCRT | Serum Concentration of Tislelizumab for Participants in the Ociperlimab + Tislelizumab + cCRT Treatment Group | Cycle 1 Day 1 | 72.20 ug/mL | Geometric Coefficient of Variation 26.27 |
| Tislelizumab + cCRT | Serum Concentration of Tislelizumab for Participants in the Ociperlimab + Tislelizumab + cCRT Treatment Group | Cycle 5 Day 1 | 97.08 ug/mL | Geometric Coefficient of Variation 23.09 |
Secondary
Serum Concentration of Tislelizumab for Participants in the Tislelizumab + cCRT Treatment Group
Serum concentrations of tislelizumab were collected for participants in the Tislelizumab + cCRT treatment group at predose (within 60 minutes prior to infusion initiation) and postdose (within 30 minutes after the completion of infusion). End of Treatment (EOT) visits occurred within 7 days after the date investigator determined that study treatment would no longer be used, or before the initiation of a new anticancer treatment, whichever occurred first.
Time frame: Predose at Day 1 of Cycles 1, 2, 5, 9, and 17; postdose on Day 1 of Cycles 1 and 5, and EOT visit (Each Cycle is 21 days)
Population: PK Analysis Set; Tislelizumab concentration data are reported here for participants in the Tislelizumab + cCRT treatment group. Only participants with available data are included at each time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ociperlimab + Tislelizumab + cCRT | Serum Concentration of Tislelizumab for Participants in the Tislelizumab + cCRT Treatment Group | Cycle 9 Day 1 | 36.98 ug/mL | Geometric Coefficient of Variation 39.63 |
| Ociperlimab + Tislelizumab + cCRT | Serum Concentration of Tislelizumab for Participants in the Tislelizumab + cCRT Treatment Group | Cycle 17 Day 1 | 41.29 ug/mL | Geometric Coefficient of Variation 55.41 |
| Ociperlimab + Tislelizumab + cCRT | Serum Concentration of Tislelizumab for Participants in the Tislelizumab + cCRT Treatment Group | Cycle 1 Day 1 | NA ug/mL | — |
| Ociperlimab + Tislelizumab + cCRT | Serum Concentration of Tislelizumab for Participants in the Tislelizumab + cCRT Treatment Group | Cycle 5 Day 1 | 37.64 ug/mL | Geometric Coefficient of Variation 47 |
| Ociperlimab + Tislelizumab + cCRT | Serum Concentration of Tislelizumab for Participants in the Tislelizumab + cCRT Treatment Group | Cycle 2 Day 1 | 19.69 ug/mL | Geometric Coefficient of Variation 27.01 |
| Tislelizumab + cCRT | Serum Concentration of Tislelizumab for Participants in the Tislelizumab + cCRT Treatment Group | End of Treatment | 40.18 ug/mL | Geometric Coefficient of Variation 139.51 |
| Tislelizumab + cCRT | Serum Concentration of Tislelizumab for Participants in the Tislelizumab + cCRT Treatment Group | Cycle 1 Day 1 | 73.41 ug/mL | Geometric Coefficient of Variation 18.53 |
| Tislelizumab + cCRT | Serum Concentration of Tislelizumab for Participants in the Tislelizumab + cCRT Treatment Group | Cycle 5 Day 1 | 100.26 ug/mL | Geometric Coefficient of Variation 29.25 |
Secondary
Time to Death or Distant Metastasis (TTDM) as Assessed by the Investigator
defined as the time from the date of randomization until the first date of distant metastasis assessed by both the IRC and investigators, or death. Distant metastasis is defined as any new lesion that is outside of the radiation field per RECIST v1.1 or proven by biopsy.
Time frame: From randomization through to the end of study, planned duration was 20 months
Population: This secondary endpoint was specified in PA 2 and excludes participants enrolled under PA 1. No participants were enrolled under PA 2.