Advanced Solid Tumors
Conditions
Brief summary
This was a dose verification, pharmacokinetic (PK) assessment of products derived from two manufacturing processes and scales (500L-FMP and 2000L-FMP; FMP: Final Manufacturing Process) and indication expansion clinical study of monoclonal antibody conducted in Chinese subjects with advanced solid tumors, with a purpose of exploring the safety, tolerability, pharmacokinetics and preliminary efficacy.
Interventions
DRUGTislelizumab
Administered intravenously
Sponsors
BeiGene
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Participants must have histologically or cytologically confirmed advanced or metastatic tumors (unresectable), have had progression or intolerability since last standard anti-tumor treatment, or have no standard treatment or have refused standard therapy. 2. Participants must be able to provide archival tumor tissues (paraffin blocks or at least 10 unstained tumor specimen slides). 3. Participants must have at least one measurable lesion as defined per RECIST criterion version 1.1. 4. Participant must have adequate organ function. 5. Females are eligible to participate in the study if they are: a) Non-childbearing potential (that is, physiologically incapable of becoming pregnant) who: * Has had hysterectomy * Has had bilateral oophorectomy * Has had bilateral tubal ligation or are post-menopausal (total cessation of menses for ≥1 year) b) Childbearing potential: * Must be willing to use a highly effective method of birth control for the duration of the study, and for at least 120 days after the last dose of tislelizumab, and have a negative urine or serum pregnancy test within 7 days of the first dose of study drug. 6. Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study. Key
Exclusion criteria
1. History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs). 2. Prior malignancy active within the previous 2 years except for the tumor under investigation in this trial, cured or locally curable cancers, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast. 3. Prior therapies targeting PD-1 or PD-L1. Active brain or leptomeningeal metastases. Participants with brain metastases are permitted if they are asymptomatic, for example, diagnosed incidentally by brain imaging, or participants with previously treated brain metastases that are asymptomatic at screening, radiographically stable and not requiring steroid medications for at least 4 weeks prior to the first administration of study treatment. 4. Participants with active autoimmune diseases or history of autoimmune diseases or immunodeficiency that may relapse should be excluded. Participants with following diseases are allowed to be enrolled for further screening: type I diabetes, hypothyroidism managed with hormone replacement therapy only, skin diseases not requiring systemic treatment (such as vitiligo, psoriasis or alopecia), or diseases not expected to recur in the absence of external triggering factors. 5. Participants should be excluded if they have a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study drug administration. 6. With uncontrollable pleural effusion, pericardial effusion or ascites requiring repeated drainage. 7. Use of any live or attenuated vaccines within 4 weeks (28 days) prior to initiation of study therapy. 8. Major surgical procedure (Grade 3 or 4) within the past 4 weeks (28 days) prior to study drug administration. 9. Prior allogeneic or solid organ transplantation. NOTE: Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Verification and PK Sub-study: Number Participants With Adverse Events | Up to approximately 23 months | Number of participants with adverse events (AEs) and serious adverse events (SAEs), as defined per NCI-CTCAE Version 4.03, including physical examination, electrocardiograms and laboratory assessments |
| Dose Verification: Recommended Dose of Tislelizumab | Up to approximately 23 months | Recommended dose of tislelizumab for indication cohorts based on safety and tolerability |
| PK Sub-study: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Tislelizumab From Two Manufacturing Processes and Scales | Predose, end of infusion, 3 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22, and Day 29 predose | Pharmacokinetics from products derived from two manufacturing scales at 500 liter and 2000 liter final manufacturing process (FMP) were evaluated |
| PK Sub-study: Area Under the Concentration-time Curve From Time 0 to 28 Days Postdose (AUC0-28d) of Tislelizumab From Two Manufacturing Processes and Scales | Predose, end of infusion, 3 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22, and Day 29 predose | Pharmacokinetics from products derived from two manufacturing scales at 500 liter and 2000 liter final manufacturing process (FMP) were evaluated |
| PK Sub-study: Maximum Observed Concentration (Cmax) of Tislelizumab From Two Manufacturing Processes and Scales | Predose, end of infusion, 3 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22, and Day 29 predose | Pharmacokinetics from products derived from two manufacturing scales at 500 liter and 2000 liter FMP were evaluated |
| Indication Expansion: Objective Response Rate | Up to approximately 3 years and 5 months | Objective response rate (ORR) is defined as the percentage of participants who achieved objective tumor response (complete response or partial response) according to RECIST Version 1.1. Indication expansion includes participants from all parts in the following indications: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), urothelial carcinoma (UC), nasopharyngeal carcinoma (NPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, and other tumor types. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Indication Expansion: Duration of Response | Up to approximately 3 years and 5 months | Duration of response for responders with complete or partial response is defined as the time interval between the date of the earliest qualifying response and the date of progressive disease or death for any cause, whichever occurs earlier as determined by Investigator per RECIST version 1.1. Indication expansion includes participants from all parts in the following indications: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), urothelial carcinoma (UC), nasopharyngeal carcinoma (NPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, and other tumor types. |
| Indication Expansion: Clinical Benefit Rate | Up to approximately 3 years and 5 months | Clinical benefit rate is defined as the percentage of participants in specific tumor types reaching confirmed CR, PR and durable stable disease (SD; at ≥ 24 weeks) in accordance with RECIST version 1.1. Indication expansion includes participants from all parts in the following indications: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), urothelial carcinoma (UC), nasopharyngeal carcinoma (NPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, and other tumor types. |
| Dose Verification: Maximum Observed Concentration (Cmax) of Tislelizumab | Predose, end of infusion, 1.5 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22 predose in Cycle 1 and Cycle 5 (21 days per cycle) | — |
| Indication Expansion: Disease Control Rate | Up to approximately 3 years and 5 months | Disease control rate is defined as the percentage of participants reaching CR, PR, and SD according to RECIST version 1.1. Indication expansion includes participants from all parts in the following indications: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), urothelial carcinoma (UC), nasopharyngeal carcinoma (NPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, and other tumor types. |
| Number of Participants With Positive Anti-drug Antibody (ADA) Status to Tislelizumab | Up to approximately 23 months | — |
| Indication Expansion: Overall Survival | Up to approximately 3 years and 5 months | Overall survival is defined as the time from the date of the first study dose to death. Indication expansion includes participants from all parts in the following indications: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), urothelial carcinoma (UC), nasopharyngeal carcinoma (NPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, and other tumor types. |
| Dose Verification: Area Under the Concentration-time Curve From Time 0 to 21 Days Postdose (AUC0-tau) of Tislelizumab | Predose, end of infusion, 1.5 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22 predose in Cycle 1 and Cycle 5 (21 days per cycle) | — |
| Dose Verification: Predose Plasma Concentration of Tislelizumab During Multiple Dosing (Ctrough) | Predose, end of infusion, 1.5 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22 predose in Cycle 1 and Cycle 5 (21 days per cycle) | — |
| Dose Verification: Apparent Terminal Half-life of Tislelizumab (t1/2) | Predose, end of infusion, 1.5 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22 predose in Cycle 1 and Cycle 5 (21 days per cycle) | — |
| Dose Verification: Clearance (Cl) | Predose, end of infusion, 1.5 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22 predose in Cycle 1 (21 days per cycle) | — |
| Indication Expansion: Progression-free Survival (PFS) | Up to approximately 3 years and 5 months | Progression-free survival is defined as the time from the date of first study dose to disease progression or death, whichever comes first, as determined by Investigator per RECIST version 1.1. Indication expansion includes participants from all parts in the following indications: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), urothelial carcinoma (UC), nasopharyngeal carcinoma (NPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, and other tumor types. |
Countries
China
Participant flow
Recruitment details
A total of 300 participants were treated with at least 1 dose of tislelizumab. This was a single arm study with 3 parts: dose verification, pharmacokinetic (PK) sub-study, and indication expansion.
Participants by arm
| Arm | Count |
|---|---|
| Tislelizumab Tislelizumab 200 mg was administered intravenously (IV) once every 3 weeks (21 days per cycle) until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator. | 300 |
| Total | 300 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Dose Verification | Death | 15 |
| Dose Verification | Withdrawal by Subject | 1 |
| Indication Expansion | Death | 152 |
| Indication Expansion | Lost to Follow-up | 7 |
| Indication Expansion | Withdrawal by Subject | 10 |
| Pharmacokinetic Sub-study | Death | 35 |
| Pharmacokinetic Sub-study | Lost to Follow-up | 4 |
| Pharmacokinetic Sub-study | Other not specified | 1 |
| Pharmacokinetic Sub-study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Tislelizumab |
|---|---|
| Age, Continuous | 55.5 Years STANDARD_DEVIATION 11.48 |
| Race/Ethnicity, Customized Chinese | 300 Participants |
| Sex: Female, Male Female | 93 Participants |
| Sex: Female, Male Male | 207 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 202 / 300 |
| other Total, other adverse events | 277 / 300 |
| serious Total, serious adverse events | 85 / 300 |
Outcome results
Primary
Dose Verification and PK Sub-study: Number Participants With Adverse Events
Number of participants with adverse events (AEs) and serious adverse events (SAEs), as defined per NCI-CTCAE Version 4.03, including physical examination, electrocardiograms and laboratory assessments
Time frame: Up to approximately 23 months
Population: The Safety Analysis Set (SAS) included all participants who received ≥ 1 dose of tislelizumab
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Verification | Dose Verification and PK Sub-study: Number Participants With Adverse Events | At least one treatment-emergent adverse event (TEAE) | 20 Participants |
| Dose Verification | Dose Verification and PK Sub-study: Number Participants With Adverse Events | TEAE Grade 3 of higher | 9 Participants |
| Dose Verification | Dose Verification and PK Sub-study: Number Participants With Adverse Events | Serious adverse event | 4 Participants |
| PK Sub-study | Dose Verification and PK Sub-study: Number Participants With Adverse Events | At least one treatment-emergent adverse event (TEAE) | 54 Participants |
| PK Sub-study | Dose Verification and PK Sub-study: Number Participants With Adverse Events | TEAE Grade 3 of higher | 21 Participants |
| PK Sub-study | Dose Verification and PK Sub-study: Number Participants With Adverse Events | Serious adverse event | 14 Participants |
Primary
Dose Verification: Recommended Dose of Tislelizumab
Recommended dose of tislelizumab for indication cohorts based on safety and tolerability
Time frame: Up to approximately 23 months
Population: The Safety Analysis Set (SAS) included all participants who received ≥ 1 dose of tislelizumab
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Verification | Dose Verification: Recommended Dose of Tislelizumab | 200 milligrams |
Primary
Indication Expansion: Objective Response Rate
Objective response rate (ORR) is defined as the percentage of participants who achieved objective tumor response (complete response or partial response) according to RECIST Version 1.1. Indication expansion includes participants from all parts in the following indications: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), urothelial carcinoma (UC), nasopharyngeal carcinoma (NPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, and other tumor types.
Time frame: Up to approximately 3 years and 5 months
Population: The Safety Analysis Set (SAS) included all participants who received ≥ 1 dose of tislelizumab; one participant is included in both MSI-H/dMMR and GC indications.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose Verification | Indication Expansion: Objective Response Rate | UC | 18.2 Percentage of participants |
| Dose Verification | Indication Expansion: Objective Response Rate | NSCLC | 17.9 Percentage of participants |
| Dose Verification | Indication Expansion: Objective Response Rate | Melanoma | 17.6 Percentage of participants |
| Dose Verification | Indication Expansion: Objective Response Rate | ESCC | 7.7 Percentage of participants |
| Dose Verification | Indication Expansion: Objective Response Rate | GC | 16.7 Percentage of participants |
| Dose Verification | Indication Expansion: Objective Response Rate | NPC | 47.6 Percentage of participants |
| Dose Verification | Indication Expansion: Objective Response Rate | RCC | 9.5 Percentage of participants |
| Dose Verification | Indication Expansion: Objective Response Rate | HCC | 16.7 Percentage of participants |
| Dose Verification | Indication Expansion: Objective Response Rate | MSI-H/dMMR | 25.0 Percentage of participants |
| Dose Verification | Indication Expansion: Objective Response Rate | Other | 9.5 Percentage of participants |
Primary
PK Sub-study: Area Under the Concentration-time Curve From Time 0 to 28 Days Postdose (AUC0-28d) of Tislelizumab From Two Manufacturing Processes and Scales
Pharmacokinetics from products derived from two manufacturing scales at 500 liter and 2000 liter final manufacturing process (FMP) were evaluated
Time frame: Predose, end of infusion, 3 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22, and Day 29 predose
Population: The PK Analysis Set included participants in the SAS for whom at least 1 valid PK parameter could be derived for tislelizumab
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Dose Verification | PK Sub-study: Area Under the Concentration-time Curve From Time 0 to 28 Days Postdose (AUC0-28d) of Tislelizumab From Two Manufacturing Processes and Scales | 500L-FMP | 810.2 µg/mL*day |
| Dose Verification | PK Sub-study: Area Under the Concentration-time Curve From Time 0 to 28 Days Postdose (AUC0-28d) of Tislelizumab From Two Manufacturing Processes and Scales | 2000L-FMP | 801.7 µg/mL*day |
Primary
PK Sub-study: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Tislelizumab From Two Manufacturing Processes and Scales
Pharmacokinetics from products derived from two manufacturing scales at 500 liter and 2000 liter final manufacturing process (FMP) were evaluated
Time frame: Predose, end of infusion, 3 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22, and Day 29 predose
Population: The PK Analysis Set included participants in the SAS for whom at least 1 valid PK parameter could be derived for tislelizumab
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Dose Verification | PK Sub-study: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Tislelizumab From Two Manufacturing Processes and Scales | 500L-FMP | 1113.9 µg/mL*day |
| Dose Verification | PK Sub-study: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Tislelizumab From Two Manufacturing Processes and Scales | 2000L-FMP | 1108 µg/mL*day |
Primary
PK Sub-study: Maximum Observed Concentration (Cmax) of Tislelizumab From Two Manufacturing Processes and Scales
Pharmacokinetics from products derived from two manufacturing scales at 500 liter and 2000 liter FMP were evaluated
Time frame: Predose, end of infusion, 3 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22, and Day 29 predose
Population: PK Analysis Set included participants in the SAS for whom at least 1 valid PK parameter could be derived for tislelizumab
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Dose Verification | PK Sub-study: Maximum Observed Concentration (Cmax) of Tislelizumab From Two Manufacturing Processes and Scales | 500L-FMP | 77.3 µg/mL |
| Dose Verification | PK Sub-study: Maximum Observed Concentration (Cmax) of Tislelizumab From Two Manufacturing Processes and Scales | 2000L-FMP | 75.7 µg/mL |
Secondary
Dose Verification: Apparent Terminal Half-life of Tislelizumab (t1/2)
Time frame: Predose, end of infusion, 1.5 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22 predose in Cycle 1 and Cycle 5 (21 days per cycle)
Population: PK Analysis Set included participants in the SAS for whom at least 1 valid PK parameter could be derived for tislelizumab
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Verification | Dose Verification: Apparent Terminal Half-life of Tislelizumab (t1/2) | Cycle 1 | 13.3 Days | Standard Deviation 2.95 |
| Dose Verification | Dose Verification: Apparent Terminal Half-life of Tislelizumab (t1/2) | Cycle 5 | 16.9 Days | Standard Deviation 3.79 |
Secondary
Dose Verification: Area Under the Concentration-time Curve From Time 0 to 21 Days Postdose (AUC0-tau) of Tislelizumab
Time frame: Predose, end of infusion, 1.5 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22 predose in Cycle 1 and Cycle 5 (21 days per cycle)
Population: PK Analysis Set included participants in the SAS for whom at least 1 valid PK parameter could be derived for tislelizumab
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Verification | Dose Verification: Area Under the Concentration-time Curve From Time 0 to 21 Days Postdose (AUC0-tau) of Tislelizumab | Cycle 1 | 600.1 µg/mL*day | Standard Deviation 144.5 |
| Dose Verification | Dose Verification: Area Under the Concentration-time Curve From Time 0 to 21 Days Postdose (AUC0-tau) of Tislelizumab | Cycle 5 | 1122 µg/mL*day | Standard Deviation 352 |
Secondary
Dose Verification: Clearance (Cl)
Time frame: Predose, end of infusion, 1.5 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22 predose in Cycle 1 (21 days per cycle)
Population: PK Analysis Set included participants in the SAS for whom at least 1 valid PK parameter could be derived for tislelizumab
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Verification | Dose Verification: Clearance (Cl) | 0.247 Liters/day | Standard Deviation 0.0918 |
Secondary
Dose Verification: Maximum Observed Concentration (Cmax) of Tislelizumab
Time frame: Predose, end of infusion, 1.5 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22 predose in Cycle 1 and Cycle 5 (21 days per cycle)
Population: PK Analysis Set included participants in the SAS for whom at least 1 valid PK parameter could be derived for tislelizumab
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Verification | Dose Verification: Maximum Observed Concentration (Cmax) of Tislelizumab | Cycle 1 | 67.8 µg/mL | Standard Deviation 12.8 |
| Dose Verification | Dose Verification: Maximum Observed Concentration (Cmax) of Tislelizumab | Cycle 5 | 131 µg/mL | Standard Deviation 37.7 |
Secondary
Dose Verification: Predose Plasma Concentration of Tislelizumab During Multiple Dosing (Ctrough)
Time frame: Predose, end of infusion, 1.5 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22 predose in Cycle 1 and Cycle 5 (21 days per cycle)
Population: PK Analysis Set included participants in the SAS for whom at least 1 valid PK parameter could be derived for tislelizumab
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Verification | Dose Verification: Predose Plasma Concentration of Tislelizumab During Multiple Dosing (Ctrough) | Cycle 1 | 15.8 µg/mL | Standard Deviation 4.73 |
| Dose Verification | Dose Verification: Predose Plasma Concentration of Tislelizumab During Multiple Dosing (Ctrough) | Cycle 5 | 31.4 µg/mL | Standard Deviation 9.55 |
Secondary
Indication Expansion: Clinical Benefit Rate
Clinical benefit rate is defined as the percentage of participants in specific tumor types reaching confirmed CR, PR and durable stable disease (SD; at ≥ 24 weeks) in accordance with RECIST version 1.1. Indication expansion includes participants from all parts in the following indications: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), urothelial carcinoma (UC), nasopharyngeal carcinoma (NPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, and other tumor types.
Time frame: Up to approximately 3 years and 5 months
Population: The Safety Analysis Set (SAS) included all participants who received ≥ 1 dose of tislelizumab; one participant is included in both MSI-H/dMMR and GC indications.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose Verification | Indication Expansion: Clinical Benefit Rate | NSCLC | 33.9 Percentage of participants |
| Dose Verification | Indication Expansion: Clinical Benefit Rate | Melanoma | 32.4 Percentage of participants |
| Dose Verification | Indication Expansion: Clinical Benefit Rate | ESCC | 15.4 Percentage of participants |
| Dose Verification | Indication Expansion: Clinical Benefit Rate | GC | 25.0 Percentage of participants |
| Dose Verification | Indication Expansion: Clinical Benefit Rate | UC | 27.3 Percentage of participants |
| Dose Verification | Indication Expansion: Clinical Benefit Rate | NPC | 61.9 Percentage of participants |
| Dose Verification | Indication Expansion: Clinical Benefit Rate | RCC | 38.1 Percentage of participants |
| Dose Verification | Indication Expansion: Clinical Benefit Rate | HCC | 38.9 Percentage of participants |
| Dose Verification | Indication Expansion: Clinical Benefit Rate | MSI-H/dMMR | 50.0 Percentage of participants |
| Dose Verification | Indication Expansion: Clinical Benefit Rate | Other | 22.2 Percentage of participants |
Secondary
Indication Expansion: Disease Control Rate
Disease control rate is defined as the percentage of participants reaching CR, PR, and SD according to RECIST version 1.1. Indication expansion includes participants from all parts in the following indications: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), urothelial carcinoma (UC), nasopharyngeal carcinoma (NPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, and other tumor types.
Time frame: Up to approximately 3 years and 5 months
Population: The Safety Analysis Set (SAS) included all participants who received ≥ 1 dose of tislelizumab; one participant is included in both MSI-H/dMMR and GC indications.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose Verification | Indication Expansion: Disease Control Rate | NSCLC | 55.4 Percentage of participants |
| Dose Verification | Indication Expansion: Disease Control Rate | Melanoma | 38.2 Percentage of participants |
| Dose Verification | Indication Expansion: Disease Control Rate | ESCC | 34.6 Percentage of participants |
| Dose Verification | Indication Expansion: Disease Control Rate | GC | 25.0 Percentage of participants |
| Dose Verification | Indication Expansion: Disease Control Rate | UC | 40.9 Percentage of participants |
| Dose Verification | Indication Expansion: Disease Control Rate | NPC | 81.0 Percentage of participants |
| Dose Verification | Indication Expansion: Disease Control Rate | RCC | 52.4 Percentage of participants |
| Dose Verification | Indication Expansion: Disease Control Rate | HCC | 55.6 Percentage of participants |
| Dose Verification | Indication Expansion: Disease Control Rate | MSI-H/dMMR | 50.0 Percentage of participants |
| Dose Verification | Indication Expansion: Disease Control Rate | Other | 31.7 Percentage of participants |
Secondary
Indication Expansion: Duration of Response
Duration of response for responders with complete or partial response is defined as the time interval between the date of the earliest qualifying response and the date of progressive disease or death for any cause, whichever occurs earlier as determined by Investigator per RECIST version 1.1. Indication expansion includes participants from all parts in the following indications: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), urothelial carcinoma (UC), nasopharyngeal carcinoma (NPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, and other tumor types.
Time frame: Up to approximately 3 years and 5 months
Population: The Safety Analysis Set (SAS) included all participants who received ≥ 1 dose of tislelizumab; one participant is included in both MSI-H/dMMR and GC indications.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Verification | Indication Expansion: Duration of Response | NSCLC | 30.4 Months |
| Dose Verification | Indication Expansion: Duration of Response | Melanoma | 12.5 Months |
| Dose Verification | Indication Expansion: Duration of Response | ESCC | NA Months |
| Dose Verification | Indication Expansion: Duration of Response | GC | NA Months |
| Dose Verification | Indication Expansion: Duration of Response | UC | NA Months |
| Dose Verification | Indication Expansion: Duration of Response | NPC | 8.8 Months |
| Dose Verification | Indication Expansion: Duration of Response | RCC | NA Months |
| Dose Verification | Indication Expansion: Duration of Response | HCC | NA Months |
| Dose Verification | Indication Expansion: Duration of Response | MSI-H/dMMR | NA Months |
| Dose Verification | Indication Expansion: Duration of Response | Other | NA Months |
Secondary
Indication Expansion: Overall Survival
Overall survival is defined as the time from the date of the first study dose to death. Indication expansion includes participants from all parts in the following indications: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), urothelial carcinoma (UC), nasopharyngeal carcinoma (NPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, and other tumor types.
Time frame: Up to approximately 3 years and 5 months
Population: The Safety Analysis Set (SAS) included all participants who received ≥ 1 dose of tislelizumab; one participant is included in both MSI-H/dMMR and GC indications.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Verification | Indication Expansion: Overall Survival | UC | 4.3 Months |
| Dose Verification | Indication Expansion: Overall Survival | NSCLC | 22.1 Months |
| Dose Verification | Indication Expansion: Overall Survival | Melanoma | 11.8 Months |
| Dose Verification | Indication Expansion: Overall Survival | ESCC | 4.8 Months |
| Dose Verification | Indication Expansion: Overall Survival | GC | 4.7 Months |
| Dose Verification | Indication Expansion: Overall Survival | NPC | 25.0 Months |
| Dose Verification | Indication Expansion: Overall Survival | RCC | 19.8 Months |
| Dose Verification | Indication Expansion: Overall Survival | HCC | 25.1 Months |
| Dose Verification | Indication Expansion: Overall Survival | MSI-H/dMMR | 19.4 Months |
| Dose Verification | Indication Expansion: Overall Survival | Other | 9.0 Months |
Secondary
Indication Expansion: Progression-free Survival (PFS)
Progression-free survival is defined as the time from the date of first study dose to disease progression or death, whichever comes first, as determined by Investigator per RECIST version 1.1. Indication expansion includes participants from all parts in the following indications: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), urothelial carcinoma (UC), nasopharyngeal carcinoma (NPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, and other tumor types.
Time frame: Up to approximately 3 years and 5 months
Population: The Safety Analysis Set (SAS) included all participants who received ≥ 1 dose of tislelizumab; one participant is included in both MSI-H/dMMR and GC indications.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Verification | Indication Expansion: Progression-free Survival (PFS) | NSCLC | 4.0 Months |
| Dose Verification | Indication Expansion: Progression-free Survival (PFS) | Melanoma | 2.2 Months |
| Dose Verification | Indication Expansion: Progression-free Survival (PFS) | ESCC | 2.1 Months |
| Dose Verification | Indication Expansion: Progression-free Survival (PFS) | GC | 2.1 Months |
| Dose Verification | Indication Expansion: Progression-free Survival (PFS) | UC | 2.1 Months |
| Dose Verification | Indication Expansion: Progression-free Survival (PFS) | NPC | 8.2 Months |
| Dose Verification | Indication Expansion: Progression-free Survival (PFS) | RCC | 4.1 Months |
| Dose Verification | Indication Expansion: Progression-free Survival (PFS) | HCC | 4.0 Months |
| Dose Verification | Indication Expansion: Progression-free Survival (PFS) | MSI-H/dMMR | 6.1 Months |
| Dose Verification | Indication Expansion: Progression-free Survival (PFS) | Other | 2.3 Months |
Secondary
Number of Participants With Positive Anti-drug Antibody (ADA) Status to Tislelizumab
Time frame: Up to approximately 23 months
Population: Evaluable participants had non-missing baseline ADA and at least 1 non-missing postbaseline ADA result.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Verification | Number of Participants With Positive Anti-drug Antibody (ADA) Status to Tislelizumab | Treatment-emergent | 43 Participants |
| Dose Verification | Number of Participants With Positive Anti-drug Antibody (ADA) Status to Tislelizumab | Treatment-boosted | 2 Participants |
| Dose Verification | Number of Participants With Positive Anti-drug Antibody (ADA) Status to Tislelizumab | Treatment-induced | 41 Participants |