Hepatocellular Carcinoma, Metastatic Hepatocellular Carcinoma, Unresectable Hepatocellular Carcinoma
Conditions
Brief summary
The primary objective of this study was to assess the preliminary antitumor activity as indicated by overall response rate (ORR) of tislelizumab in combination with lenvatinib in participants with unresectable locally advanced or metastatic hepatocellular carcinoma (HCC) by central site imaging facility per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Interventions
DRUGLenvatinib
Capsules administered orally once daily
DRUGTislelizumab
200 mg intravenous (IV) infusion administered on Day 1 of each cycle
Sponsors
BeiGene
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments 2. Unresectable locally advanced or metastatic HCC, which must be confirmed by histologically or cytologically. Fibrolamellar, sarcomatoid, or mixed cholangiocarcinoma histology confirmed by histologically or cytologically is excluded. 3. Barcelona Clinic Liver Cancer (BCLC) Stage C disease or BCLC Stage B disease that is not amenable to or has progressed after loco-regional therapy and is not amenable to a curative treatment approach 4. Did not receive any systemic treatment before and is unwilling to accept standard of care treatment or not suitable for standard of care treatment as judged by investigators 5. At least 1 measurable lesion as defined by RECIST v1.1 6. European Cancer Oncology Group (ECOG) Performance Status ≤ 1 7. Child-Pugh A classification for liver function assessed within 7 days of first dose of study drugs Key
Exclusion criteria
1. Active autoimmune diseases or history of autoimmune diseases that may relapse 2. Any active malignancy ≤ 2 years before the first dose of study drugs except for 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 the cervix or breast) 3. Uncontrolled diabetes or \> Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium despite standard medical management, or ≥ Grade 3 hypoalbuminemia ≤ 14 days before the first dose of study drugs 4. Any known brain or leptomeningeal metastases 5. Concurrent participation in another therapeutic clinical study NOT: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) as Assessed by Central Imaging Facility Based on RECIST v1.1 | Response was assessed every 6 weeks for the first year and approximately every 9 weeks thereafter through December 2022; up to 27 months | ORR was defined as the percentage of participants achieving the best overall response (BOR) of complete response (CR) or partial response (PR). The 95% confidence interval (CI) was estimated using the Clopper-Pearson method. Per Response evaluation criteria in solid tumors (RECIST) version (v)1.1., CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) as Assessed by the Investigator Based on RECIST v1.1 | Response was assessed every 6 weeks for the first year and approximately every 9 weeks thereafter through December 2022; i.e., up to 27 months | ORR was defined as the percentage of participants achieving the BOR of CR or PR. The 95% CI was estimated using the Clopper-Pearson method. Per RECIST v1.1., CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Objective Response Rate (ORR) as Assessed by the Investigator and Central Site Imaging Facility Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) | Response was assessed every 6 weeks for the first year and approximately every 9 weeks thereafter through December 2022; up to 27 months | ORR was defined as the percentage of participants achieving the BOR of CR or PR. The 95% CI was estimated using the Clopper-Pearson method. Per modified RECIST (mRECIST), CR was defined as the disappearance of any intratumoral arterial enhancement in all target lesions. PR: at least a 30% decrease in the sum of diameters of viable (contrast enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions. |
| Objective Response Rate (ORR) as Assessed by the Investigator and Central Site Imaging Facility Based on Immune Related Response Evaluation Criteria in Solid Tumors (iRECIST) | Response was assessed every 6 weeks for the first year and approximately every 9 weeks thereafter through December 2022; up to 27 months | ORR was defined as the percentage of participants achieving the BOR of immune complete response (iCR) or partial response (iPR). The 95% CI was estimated using the Clopper-Pearson method. Per iRECIST, iCR was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be \<10 mm in the short axis. iPR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. iRECIST is a modification to RECIST that considers unique patterns of atypical response in immunotherapy and enables treatment beyond initial radiographic progression. |
| Duration of Response (DOR) As Assessed by The Investigator Based on RECIST v1.1 | From the date of earliest response to the date of first documentation of disease progression or death, whichever occurred first (up to 35 months) | DOR was defined as the time interval between the date of the earliest qualifying response (CR or PR) and the date of PD or death (whichever occurred earlier). DOR was estimated using the Kaplan-Meier method. Per RECIST v1.1., CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. |
| Duration of Response (DOR) As Assessed by The Central Site Imaging Facility Based on RECIST v1.1 | From the date of earliest response to the date of first documentation of disease progression or death, whichever occurred first (up to 35 months) | DOR was defined as the time interval between the date of the earliest qualifying response (CR or PR) and the date of PD or death (whichever occurred earlier). DOR was estimated using the Kaplan-Meier method. Per RECIST v1.1., CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. |
| Duration of Response (DOR) As Assessed by The Investigator Based on mRECIST | From the date of earliest response to the date of first documentation of disease progression or death, whichever occurred first (up to 35 months) | DOR was defined as the time interval between the date of the earliest qualifying response (CR or PR) and the date of PD or death (whichever occurs earlier). DOR was estimated using the Kaplan-Meier method. Per mRECIST, CR was defined as the disappearance of any intratumoral arterial enhancement in all target lesions. PR: at least a 30% decrease in the sum of diameters of viable (contrast enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions. PD: an increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since the treatment started. |
| Duration of Response (DOR) As Assessed by the Central Site Imaging Facility Based on mRECIST | From the date of earliest response to the date of first documentation of disease progression or death, whichever occurred first (up to 35 months) | DOR was defined as the time interval between the date of the earliest qualifying response (CR or PR) and the date of PD or death (whichever occurs earlier). DOR was estimated using the Kaplan-Meier method. Per mRECIST, CR was defined as the disappearance of any intratumoral arterial enhancement in all target lesions. PR: at least a 30% decrease in the sum of diameters of viable (contrast enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions. PD: an increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since the treatment started. |
| Duration of Response (DOR) As Assessed by The Investigator Based on iRECIST | From the date of earliest response to the date of first documentation of disease progression or death, whichever occurred first (up to 35 months) | DOR was defined as the time interval between the date of the earliest qualifying response (iCR or iPR) and the date of confirmed progressive disease (iCPD) or death (whichever occurs earlier). DOR was estimated using the Kaplan-Meier method. Per iRECIST, iCR was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be \<10 mm in the short axis. iPR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. iRECIST is a modification to RECIST that considers unique patterns of atypical response in immunotherapy and enables treatment beyond initial radiographic progression. |
| Duration of Response (DOR) As Assessed by The Central Site Imaging Facility Based on iRECIST | From the date of earliest response to the date of first documentation of disease progression or death, whichever occurs first (up to 35 months) | DOR was defined as the time interval between the date of the earliest qualifying response (iCR or iPR) and the date of confirmed progressive disease (iCPD) or death (whichever occurs earlier). DOR was estimated using the Kaplan-Meier method. Per iRECIST, iCR was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be \<10 mm in the short axis. iPR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. iRECIST is a modification to RECIST that considers unique patterns of atypical response in immunotherapy and enables treatment beyond initial radiographic progression. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and TEAEs Leading to Treatment Discontinuation and Modification | From the date of the first dose of study drug up to 30 days after last dose of study drug (maximum time on treatment was 12 months) | A TEAE was defined as adverse event (AE) that had an onset date or a worsening in severity from baseline (pre-treatment) on or after the first dose of study drug(s) and up to 30 days following study drug(s) discontinuation or initiation of new anticancer therapy, whichever occurs first determined according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. SAE: any untoward medical occurrence at any dose: resulted in death; was life threatening; required prolong inpatient hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect or was considered a significant medical event by the investigator. |
| Disease Control Rate (DCR) As Assessed by The Investigator and Central Site Imaging Facility Based on mRECIST | Response was assessed every 6 weeks for the first year and approximately every 9 weeks thereafter through December 2022; up to 27 months | DCR was defined as the percentage of participants with BOR of CR, PR or SD. Participants without post-baseline tumor assessment were considered as failure in DCR. The 95% CI was estimated using the Clopper-Pearson method. Per mRECIST, CR was defined as the disappearance of any intratumoral arterial enhancement in all target lesions. PR: at least a 30% decrease in the sum of diameters of viable (contrast enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions. Stable disease (SD): any cases that do not qualify for either partial response or progressive disease. |
| Disease Control Rate (DCR) As Assessed by The Investigator and Central Site Imaging Facility Based on iRECIST | Response was assessed every 6 weeks for the first year and approximately every 9 weeks thereafter through December 2022; up to 27 months | DCR was defined as the percentage of participants with BOR of iCR, iPR or immune stable disease (iSD). Participants without post-baseline tumor assessment were considered a failure in DCR. The 95% CI was estimated using the Clopper-Pearson method. Per iRECIST, iCR was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be \<10 mm in the short axis. iPR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. iSD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. iRECIST is a modification to RECIST that considers unique patterns of atypical response in immunotherapy and enables treatment beyond initial radiographic progression. |
| Progression Free Survival (PFS) As Assessed by The Investigator Based on RECIST v1.1 | From date of first dose of study drug until the date of first documented progression or date of death from any cause, whichever came first (up to 35 months) | PFS was defined as the time from the date of the first dose of study drug(s) to the date of the confirmed documentation of PD or death, whichever occurred first. PFS was estimated using the Kaplan-Meier method. Per RECIST v1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. |
| Progression Free Survival (PFS) As Assessed by The Central Site Imaging Facility Based on RECIST v1.1 | From date of first dose of study drug until the date of first documented progression or date of death from any cause, whichever came first (up to 35 months) | PFS was defined as the time from the date of the first dose of study drug(s) to the date of the confirmed documentation of PD or death, whichever occurred first. PFS was estimated using the Kaplan-Meier method. Per RECIST v1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. |
| Progression Free Survival (PFS) As Assessed by The Investigator Based on mRECIST | From date of first dose of study drug until the date of first documented progression or date of death from any cause, whichever came first (up to 35 months) | PFS was defined as the time from the date of the first dose of study drug(s) to the date of the confirmed documentation of PD or death, whichever occurs first. PFS was estimated using the Kaplan-Meier method. Per mRECIST, PD was defined as an increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since the treatment started. |
| Progression Free Survival (PFS) As Assessed by The Central Site Imaging Facility Based on mRECIST | From date of first dose of study drug until the date of first documented progression or date of death from any cause, whichever came first (up to 35 months) | PFS was defined as the time from the date of the first dose of study drug(s) to the date of the confirmed documentation of PD or death, whichever occurs first. PFS was estimated using the Kaplan-Meier method. Per mRECIST, PD was defined as an increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since the treatment started. |
| Progression Free Survival (PFS) As Assessed by The Investigator Based on iRECIST | From date of first dose of study drug until the date of first documented progression or date of death from any cause, whichever came first (up to 35 months) | PFS was defined as the time from the date of the first dose of study drug(s) to the date of the confirmed documentation of progressive disease (iCPD) or death, whichever occurs first. PFS was estimated using the Kaplan-Meier method. Per iRECIST v1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. iRECIST is a modification to RECIST that considers unique patterns of atypical response in immunotherapy and enables treatment beyond initial radiographic progression. |
| Progression Free Survival (PFS) As Assessed by The Central Site Imaging Facility Based on iRECIST | From date of first dose of study drug until the date of first documented progression or date of death from any cause, whichever came first (up to 35 months) | PFS was defined as the time from the date of the first dose of study drug(s) to the date of the confirmed documentation of progressive disease (iCPD) or death, whichever occurs first. PFS was estimated using the Kaplan-Meier method. Per iRECIST v1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. iRECIST is a modification to RECIST that considers unique patterns of atypical response in immunotherapy and enables treatment beyond initial radiographic progression. |
| Disease Control Rate (DCR) As Assessed by The Investigator and Central Site Imaging Facility Based on RECIST v1.1 | Response was assessed every 6 weeks for the first year and approximately every 9 weeks thereafter through December 2022; up to 27 months | DCR was defined as the percentage of participants with BOR of CR, PR or SD. Participants without post-baseline tumor assessment were considered as failure in DCR. The 95% CI was estimated using the Clopper-Pearson method. Per RECIST v1.1., CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. |
Countries
China
Participant flow
Recruitment details
The study was conducted at 9 study sites in China.
Pre-assignment details
The study consisted of two parts: Part 1 (Safety run-in part) and Part 2 (Extension part). Results were planned to be reported and analyzed combined for Part 1 (safety-run) and Part 2 of the study as all participants received the same treatment.
Participants by arm
| Arm | Count |
|---|---|
| Lenvatinib With Tislelizumab Participants received lenvatinib based on baseline weight (12 mg or 8 mg once daily for participants with a baseline weight of \>= 60 kg or \< 60 kg, respectively) along with tislelizumab 200 mg on Day 1 of each 21-day cycle (once every 3 weeks) until disease progression, unacceptable toxicity, or withdrawal for other reasons, whichever occurred first. | 64 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 17 |
| Overall Study | Lost to Follow-up | 5 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Lenvatinib With Tislelizumab |
|---|---|
| Age, Continuous | 51.1 years STANDARD_DEVIATION 11.24 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 64 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 64 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 17 / 64 |
| other Total, other adverse events | 63 / 64 |
| serious Total, serious adverse events | 11 / 64 |
Outcome results
Primary
Overall Response Rate (ORR) as Assessed by Central Imaging Facility Based on RECIST v1.1
ORR was defined as the percentage of participants achieving the best overall response (BOR) of complete response (CR) or partial response (PR). The 95% confidence interval (CI) was estimated using the Clopper-Pearson method. Per Response evaluation criteria in solid tumors (RECIST) version (v)1.1., CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Response was assessed every 6 weeks for the first year and approximately every 9 weeks thereafter through December 2022; up to 27 months
Population: Analysis was performed on Efficacy-Evaluable Analysis Set (EFF) which included all dosed participants with measurable disease at baseline per RECIST v1.1 and who had at least one evaluable post-baseline tumor assessment unless treatment was discontinued due to clinical disease progression or death before the first post-treatment tumor assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lenvatinib With Tislelizumab | Overall Response Rate (ORR) as Assessed by Central Imaging Facility Based on RECIST v1.1 | 38.7 percentage of participants |
p-value: 0.0002Binomial exact test
Secondary
Disease Control Rate (DCR) As Assessed by The Investigator and Central Site Imaging Facility Based on iRECIST
DCR was defined as the percentage of participants with BOR of iCR, iPR or immune stable disease (iSD). Participants without post-baseline tumor assessment were considered a failure in DCR. The 95% CI was estimated using the Clopper-Pearson method. Per iRECIST, iCR was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be \<10 mm in the short axis. iPR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. iSD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. iRECIST is a modification to RECIST that considers unique patterns of atypical response in immunotherapy and enables treatment beyond initial radiographic progression.
Time frame: Response was assessed every 6 weeks for the first year and approximately every 9 weeks thereafter through December 2022; up to 27 months
Population: Analysis was performed on Efficacy-Evaluable Analysis Set (EFF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lenvatinib With Tislelizumab | Disease Control Rate (DCR) As Assessed by The Investigator and Central Site Imaging Facility Based on iRECIST | By investigator | 88.7 percentage of participants |
| Lenvatinib With Tislelizumab | Disease Control Rate (DCR) As Assessed by The Investigator and Central Site Imaging Facility Based on iRECIST | By Central Site Imaging Facility | 90.3 percentage of participants |
Secondary
Disease Control Rate (DCR) As Assessed by The Investigator and Central Site Imaging Facility Based on mRECIST
DCR was defined as the percentage of participants with BOR of CR, PR or SD. Participants without post-baseline tumor assessment were considered as failure in DCR. The 95% CI was estimated using the Clopper-Pearson method. Per mRECIST, CR was defined as the disappearance of any intratumoral arterial enhancement in all target lesions. PR: at least a 30% decrease in the sum of diameters of viable (contrast enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions. Stable disease (SD): any cases that do not qualify for either partial response or progressive disease.
Time frame: Response was assessed every 6 weeks for the first year and approximately every 9 weeks thereafter through December 2022; up to 27 months
Population: Analysis was performed on Efficacy-Evaluable Analysis Set (EFF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lenvatinib With Tislelizumab | Disease Control Rate (DCR) As Assessed by The Investigator and Central Site Imaging Facility Based on mRECIST | By investigator | 85.5 percentage of participants |
| Lenvatinib With Tislelizumab | Disease Control Rate (DCR) As Assessed by The Investigator and Central Site Imaging Facility Based on mRECIST | By Central Site Imaging Facility | 90.3 percentage of participants |
Secondary
Disease Control Rate (DCR) As Assessed by The Investigator and Central Site Imaging Facility Based on RECIST v1.1
DCR was defined as the percentage of participants with BOR of CR, PR or SD. Participants without post-baseline tumor assessment were considered as failure in DCR. The 95% CI was estimated using the Clopper-Pearson method. Per RECIST v1.1., CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time frame: Response was assessed every 6 weeks for the first year and approximately every 9 weeks thereafter through December 2022; up to 27 months
Population: Analysis was performed on Efficacy-Evaluable Analysis Set (EFF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lenvatinib With Tislelizumab | Disease Control Rate (DCR) As Assessed by The Investigator and Central Site Imaging Facility Based on RECIST v1.1 | By investigator | 85.5 percentage of participants |
| Lenvatinib With Tislelizumab | Disease Control Rate (DCR) As Assessed by The Investigator and Central Site Imaging Facility Based on RECIST v1.1 | By Central Site Imaging Facility | 90.3 percentage of participants |
Secondary
Duration of Response (DOR) As Assessed by The Central Site Imaging Facility Based on iRECIST
DOR was defined as the time interval between the date of the earliest qualifying response (iCR or iPR) and the date of confirmed progressive disease (iCPD) or death (whichever occurs earlier). DOR was estimated using the Kaplan-Meier method. Per iRECIST, iCR was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be \<10 mm in the short axis. iPR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. iRECIST is a modification to RECIST that considers unique patterns of atypical response in immunotherapy and enables treatment beyond initial radiographic progression.
Time frame: From the date of earliest response to the date of first documentation of disease progression or death, whichever occurs first (up to 35 months)
Population: Analysis was performed on Efficacy-Evaluable Analysis Set (EFF) on the subset of participants with a response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenvatinib With Tislelizumab | Duration of Response (DOR) As Assessed by The Central Site Imaging Facility Based on iRECIST | NA months |
Secondary
Duration of Response (DOR) As Assessed by the Central Site Imaging Facility Based on mRECIST
DOR was defined as the time interval between the date of the earliest qualifying response (CR or PR) and the date of PD or death (whichever occurs earlier). DOR was estimated using the Kaplan-Meier method. Per mRECIST, CR was defined as the disappearance of any intratumoral arterial enhancement in all target lesions. PR: at least a 30% decrease in the sum of diameters of viable (contrast enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions. PD: an increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since the treatment started.
Time frame: From the date of earliest response to the date of first documentation of disease progression or death, whichever occurred first (up to 35 months)
Population: Analysis was performed on Efficacy-Evaluable Analysis Set (EFF) on the subset of participants with a response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenvatinib With Tislelizumab | Duration of Response (DOR) As Assessed by the Central Site Imaging Facility Based on mRECIST | NA months |
Secondary
Duration of Response (DOR) As Assessed by The Central Site Imaging Facility Based on RECIST v1.1
DOR was defined as the time interval between the date of the earliest qualifying response (CR or PR) and the date of PD or death (whichever occurred earlier). DOR was estimated using the Kaplan-Meier method. Per RECIST v1.1., CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.
Time frame: From the date of earliest response to the date of first documentation of disease progression or death, whichever occurred first (up to 35 months)
Population: Analysis was performed on Efficacy-Evaluable Analysis Set (EFF) on the subset of participants with a response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenvatinib With Tislelizumab | Duration of Response (DOR) As Assessed by The Central Site Imaging Facility Based on RECIST v1.1 | NA months |
Secondary
Duration of Response (DOR) As Assessed by The Investigator Based on iRECIST
DOR was defined as the time interval between the date of the earliest qualifying response (iCR or iPR) and the date of confirmed progressive disease (iCPD) or death (whichever occurs earlier). DOR was estimated using the Kaplan-Meier method. Per iRECIST, iCR was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be \<10 mm in the short axis. iPR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. iRECIST is a modification to RECIST that considers unique patterns of atypical response in immunotherapy and enables treatment beyond initial radiographic progression.
Time frame: From the date of earliest response to the date of first documentation of disease progression or death, whichever occurred first (up to 35 months)
Population: Analysis was performed on Efficacy-Evaluable Analysis Set (EFF) on the subset of participants with a response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenvatinib With Tislelizumab | Duration of Response (DOR) As Assessed by The Investigator Based on iRECIST | NA months |
Secondary
Duration of Response (DOR) As Assessed by The Investigator Based on mRECIST
DOR was defined as the time interval between the date of the earliest qualifying response (CR or PR) and the date of PD or death (whichever occurs earlier). DOR was estimated using the Kaplan-Meier method. Per mRECIST, CR was defined as the disappearance of any intratumoral arterial enhancement in all target lesions. PR: at least a 30% decrease in the sum of diameters of viable (contrast enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions. PD: an increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since the treatment started.
Time frame: From the date of earliest response to the date of first documentation of disease progression or death, whichever occurred first (up to 35 months)
Population: Analysis was performed on Efficacy-Evaluable Analysis Set (EFF) on the subset of participants with a response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenvatinib With Tislelizumab | Duration of Response (DOR) As Assessed by The Investigator Based on mRECIST | 9.7 months |
Secondary
Duration of Response (DOR) As Assessed by The Investigator Based on RECIST v1.1
DOR was defined as the time interval between the date of the earliest qualifying response (CR or PR) and the date of PD or death (whichever occurred earlier). DOR was estimated using the Kaplan-Meier method. Per RECIST v1.1., CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.
Time frame: From the date of earliest response to the date of first documentation of disease progression or death, whichever occurred first (up to 35 months)
Population: Analysis was performed on Efficacy-Evaluable Analysis Set (EFF) on the subset of participants with a response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenvatinib With Tislelizumab | Duration of Response (DOR) As Assessed by The Investigator Based on RECIST v1.1 | NA months |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and TEAEs Leading to Treatment Discontinuation and Modification
A TEAE was defined as adverse event (AE) that had an onset date or a worsening in severity from baseline (pre-treatment) on or after the first dose of study drug(s) and up to 30 days following study drug(s) discontinuation or initiation of new anticancer therapy, whichever occurs first determined according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. SAE: any untoward medical occurrence at any dose: resulted in death; was life threatening; required prolong inpatient hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect or was considered a significant medical event by the investigator.
Time frame: From the date of the first dose of study drug up to 30 days after last dose of study drug (maximum time on treatment was 12 months)
Population: Analysis was performed on safety analysis set which included all participants who received at least 1 dose of any study drug (any component for the combination therapy).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lenvatinib With Tislelizumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and TEAEs Leading to Treatment Discontinuation and Modification | TEAE | 64 Participants |
| Lenvatinib With Tislelizumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and TEAEs Leading to Treatment Discontinuation and Modification | TESAE | 11 Participants |
| Lenvatinib With Tislelizumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and TEAEs Leading to Treatment Discontinuation and Modification | TEAE leading to treatment discontinuation | 4 Participants |
| Lenvatinib With Tislelizumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and TEAEs Leading to Treatment Discontinuation and Modification | TEAE leading to dose modification | 37 Participants |
Secondary
Objective Response Rate (ORR) as Assessed by the Investigator and Central Site Imaging Facility Based on Immune Related Response Evaluation Criteria in Solid Tumors (iRECIST)
ORR was defined as the percentage of participants achieving the BOR of immune complete response (iCR) or partial response (iPR). The 95% CI was estimated using the Clopper-Pearson method. Per iRECIST, iCR was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be \<10 mm in the short axis. iPR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. iRECIST is a modification to RECIST that considers unique patterns of atypical response in immunotherapy and enables treatment beyond initial radiographic progression.
Time frame: Response was assessed every 6 weeks for the first year and approximately every 9 weeks thereafter through December 2022; up to 27 months
Population: Analysis was performed on Efficacy-Evaluable Analysis Set (EFF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lenvatinib With Tislelizumab | Objective Response Rate (ORR) as Assessed by the Investigator and Central Site Imaging Facility Based on Immune Related Response Evaluation Criteria in Solid Tumors (iRECIST) | By investigator | 43.5 percentage of participants |
| Lenvatinib With Tislelizumab | Objective Response Rate (ORR) as Assessed by the Investigator and Central Site Imaging Facility Based on Immune Related Response Evaluation Criteria in Solid Tumors (iRECIST) | By Central Site Imaging Facility | 38.7 percentage of participants |
Comparison: ORR as Assessed by the Investigatorp-value: <0.0001Binomial exact test
Comparison: ORR as Assessed by Central Site Imaging Facilityp-value: 0.0002Binomial exact test
Secondary
Objective Response Rate (ORR) as Assessed by the Investigator and Central Site Imaging Facility Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
ORR was defined as the percentage of participants achieving the BOR of CR or PR. The 95% CI was estimated using the Clopper-Pearson method. Per modified RECIST (mRECIST), CR was defined as the disappearance of any intratumoral arterial enhancement in all target lesions. PR: at least a 30% decrease in the sum of diameters of viable (contrast enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions.
Time frame: Response was assessed every 6 weeks for the first year and approximately every 9 weeks thereafter through December 2022; up to 27 months
Population: Analysis was performed on Efficacy-Evaluable Analysis Set (EFF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lenvatinib With Tislelizumab | Objective Response Rate (ORR) as Assessed by the Investigator and Central Site Imaging Facility Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) | By investigator | 46.8 percentage of participants |
| Lenvatinib With Tislelizumab | Objective Response Rate (ORR) as Assessed by the Investigator and Central Site Imaging Facility Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) | By Central Site Imaging Facility | 46.8 percentage of participants |
Comparison: ORR as Assessed by the Investigatorp-value: <0.0001Binomial exact test
Comparison: ORR as Assessed by Central Site Imaging Facilityp-value: <0.0001Binomial exact test
Secondary
Objective Response Rate (ORR) as Assessed by the Investigator Based on RECIST v1.1
ORR was defined as the percentage of participants achieving the BOR of CR or PR. The 95% CI was estimated using the Clopper-Pearson method. Per RECIST v1.1., CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Response was assessed every 6 weeks for the first year and approximately every 9 weeks thereafter through December 2022; i.e., up to 27 months
Population: Analysis was performed on Efficacy-Evaluable Analysis Set (EFF).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lenvatinib With Tislelizumab | Objective Response Rate (ORR) as Assessed by the Investigator Based on RECIST v1.1 | 41.9 percentage of participants |
p-value: <0.0001Binomial exact test
Secondary
Progression Free Survival (PFS) As Assessed by The Central Site Imaging Facility Based on iRECIST
PFS was defined as the time from the date of the first dose of study drug(s) to the date of the confirmed documentation of progressive disease (iCPD) or death, whichever occurs first. PFS was estimated using the Kaplan-Meier method. Per iRECIST v1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. iRECIST is a modification to RECIST that considers unique patterns of atypical response in immunotherapy and enables treatment beyond initial radiographic progression.
Time frame: From date of first dose of study drug until the date of first documented progression or date of death from any cause, whichever came first (up to 35 months)
Population: Analysis was performed on Efficacy-Evaluable Analysis Set (EFF).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenvatinib With Tislelizumab | Progression Free Survival (PFS) As Assessed by The Central Site Imaging Facility Based on iRECIST | 8.2 months |
Secondary
Progression Free Survival (PFS) As Assessed by The Central Site Imaging Facility Based on mRECIST
PFS was defined as the time from the date of the first dose of study drug(s) to the date of the confirmed documentation of PD or death, whichever occurs first. PFS was estimated using the Kaplan-Meier method. Per mRECIST, PD was defined as an increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since the treatment started.
Time frame: From date of first dose of study drug until the date of first documented progression or date of death from any cause, whichever came first (up to 35 months)
Population: Analysis was performed on Efficacy-Evaluable Analysis Set (EFF).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenvatinib With Tislelizumab | Progression Free Survival (PFS) As Assessed by The Central Site Imaging Facility Based on mRECIST | 8.3 months |
Secondary
Progression Free Survival (PFS) As Assessed by The Central Site Imaging Facility Based on RECIST v1.1
PFS was defined as the time from the date of the first dose of study drug(s) to the date of the confirmed documentation of PD or death, whichever occurred first. PFS was estimated using the Kaplan-Meier method. Per RECIST v1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.
Time frame: From date of first dose of study drug until the date of first documented progression or date of death from any cause, whichever came first (up to 35 months)
Population: Analysis was performed on Efficacy-Evaluable Analysis Set (EFF).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenvatinib With Tislelizumab | Progression Free Survival (PFS) As Assessed by The Central Site Imaging Facility Based on RECIST v1.1 | 8.2 months |
Secondary
Progression Free Survival (PFS) As Assessed by The Investigator Based on iRECIST
PFS was defined as the time from the date of the first dose of study drug(s) to the date of the confirmed documentation of progressive disease (iCPD) or death, whichever occurs first. PFS was estimated using the Kaplan-Meier method. Per iRECIST v1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. iRECIST is a modification to RECIST that considers unique patterns of atypical response in immunotherapy and enables treatment beyond initial radiographic progression.
Time frame: From date of first dose of study drug until the date of first documented progression or date of death from any cause, whichever came first (up to 35 months)
Population: Analysis was performed on Efficacy-Evaluable Analysis Set (EFF).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenvatinib With Tislelizumab | Progression Free Survival (PFS) As Assessed by The Investigator Based on iRECIST | 11.1 months |
Secondary
Progression Free Survival (PFS) As Assessed by The Investigator Based on mRECIST
PFS was defined as the time from the date of the first dose of study drug(s) to the date of the confirmed documentation of PD or death, whichever occurs first. PFS was estimated using the Kaplan-Meier method. Per mRECIST, PD was defined as an increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since the treatment started.
Time frame: From date of first dose of study drug until the date of first documented progression or date of death from any cause, whichever came first (up to 35 months)
Population: Analysis was performed on Efficacy-Evaluable Analysis Set (EFF).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenvatinib With Tislelizumab | Progression Free Survival (PFS) As Assessed by The Investigator Based on mRECIST | 6.9 months |
Secondary
Progression Free Survival (PFS) As Assessed by The Investigator Based on RECIST v1.1
PFS was defined as the time from the date of the first dose of study drug(s) to the date of the confirmed documentation of PD or death, whichever occurred first. PFS was estimated using the Kaplan-Meier method. Per RECIST v1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.
Time frame: From date of first dose of study drug until the date of first documented progression or date of death from any cause, whichever came first (up to 35 months)
Population: Analysis was performed on Efficacy-Evaluable Analysis Set (EFF).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenvatinib With Tislelizumab | Progression Free Survival (PFS) As Assessed by The Investigator Based on RECIST v1.1 | 9.6 months |