Carcinoma, Hepatocellular, Gastric/Gastroesophageal Junction Cancer
Conditions
Keywords
Carcinoma, HCC, G/GEJ Cancer
Brief summary
The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics and preliminary antitumor activity of sitravatinib as monotherapy and in combination with tislelizumab in participants with unresectable locally advanced or metastatic hepatocellular carcinoma (HCC) or gastric/gastroesophageal junction (G/GEJ) cancer.
Detailed description
This was an open-label, multicenter Phase 1/2 clinical study for participants with histologically or cytologically confirmed unresectable locally advanced or metastatic HCC or G/GEJ cancer. All participants received study treatment (s) until progressive disease, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor.
Interventions
DRUGSitravatinib
Administered orally as a capsule
DRUGTislelizumab
Administered intravenously
Sponsors
BeiGene
Study design
Allocation
NON_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: * Histologically or cytologically confirmed, unresectable, locally advanced, or metastatic HCC/gastric cancer/GEJ cancer * Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments * 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) * Adequate organ function * Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and ≥ 120 days after the last dose of study drug(s), and have a negative serum pregnancy test ≤ 7 days of first dose of study drug(s) * Nonsterile males must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 120 days after the last dose of study drug(s) * Failed current standard-of-care treatment, or standard-of-care treatment is considered not appropriate at present Key
Exclusion criteria
* Active leptomeningeal disease or uncontrolled brain metastasis * Active autoimmune diseases or history of autoimmune diseases that may relapse * Any active malignancy ≤ 2 years before first dose of study drug(s) * History of interstitial lung disease, noninfectious pneumonitis or uncontrolled diseases including pulmonary fibrosis or acute lung diseases * Severe chronic or active infections (including tuberculosis infection) requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to first dose of study drug(s) * Known history of human immunodeficiency virus (HIV) infection * Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers. * Any major surgical procedure requiring general anesthesia ≤ 28 days before the first dose of study drug(s) * Prior allogeneic stem cell transplantation or organ transplantation * Inadequately controlled hypertension (defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg) * Bleeding or thrombotic disorders or use of anticoagulants such as warfarin or similar agents requiring therapeutic international normalized ratio (INR) monitoring * Any systemic chemotherapy within 28 days of the first dose of study drug(s) or hormone therapy, targeted therapy, or any investigational therapies * Toxicities (as a result of prior anticancer therapy) that have not recovered to baseline or stabilized, except for adverse events not considered a likely safety risk (eg, alopecia, neuropathy, and specific laboratory abnormalities) * Inability to swallow capsules or disease significantly affecting gastrointestinal function * Pregnant or breastfeeding woman NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Up to approximately 4 years and 1 month | Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0), including relevant physical examination, electrocardiograms, and laboratory assessments. Safety analysis set is presented by dose, as prespecified in the statistical analysis plan (SAP). |
| Objective Response Rate (ORR) | Up to approximately 4 years and 1 month | ORR is defined as the percentage of participants whose best overall response (BOR) is the confirmed complete response (CR) or partial response (PR) assessed by investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Efficacy evaluable analysis set is presented by indication group, as prespecified in the statistical analysis plan. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Up to approximately 4 years and 1 month | PFS is defined as the time from the date of first dose to the date of first documentation of progressive disease assessed by the investigator per RECIST v1.1 or death, whichever occurs first. Safety analysis set is presented by indication group, as prespecified in the statistical analysis plan. |
| Maximum Plasma Concentration (Cmax) for Sitravatinib | Predose and up to 24 hours postdose on Cycle 1 Day 1 (C1D1) and Cycle 1 Day 21 (C1D21) (21 days in each cycle) | — |
| Time to Maximum Plasma Concentration (Tmax) for Sitravatinib | Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle) | — |
| Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Time Point (AUC(0-t)) for Sitravatinib | Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle) | — |
| Duration of Response (DOR) | Up to approximately 4 years and 1 month | DOR is defined as the time from the first determination of an objective response until the first documentation of progressive disease as assessed by investigator per RECIST v1.1, or death, whichever comes first. Results are reported for indication groups with responders, defined as complete response (CR) or partial response (PR). Efficacy evaluable analysis set is presented by indication group, as prespecified in the statistical analysis plan. |
| Area Under the Plasma Concentration-time Curve During the Dosing Interval (AUC(0-tau)) for Sitravatinib | Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle) | — |
| Observed Accumulation Ratio (Ro) for AUC(0-tau) for Sitravatinib | Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle) | — |
| Observed Accumulation Ratio (Ro) for Cmax for Sitravatinib | Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle) | — |
| Plasma Concentrations of Sitravatinib | Predose and 6 hours postdose in Cycle 5 Day 1 (21 days in each cycle) | — |
| Clearance After Oral Administration (CL/F) for Sitravatinib | Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle) | — |
| Disease Control Rate (DCR) | Up to approximately 4 years and 1 month | DCR is defined as the percentage of participants with BOR as CR, PR, or stable disease (SD) assessed by investigator per RECIST v1.1. Efficacy evaluable analysis set is presented by indication group, as prespecified in the statistical analysis plan. |
Countries
China
Participant flow
Recruitment details
This study was conducted at multiple sites in China.
Participants by arm
| Arm | Count |
|---|---|
| Sitravatinib Monotherapy: 80 mg Sitravatinib 80 mg orally once daily in 21-day cycles in participants with unresectable locally advanced or metastatic HCC or G/GEJ cancer | 3 |
| Sitravatinib Monotherapy: 120 mg Sitravatinib 120 mg orally once daily in 21-day cycles in participants with unresectable locally advanced or metastatic HCC or G/GEJ cancer | 24 |
| Sitravatinib 80 mg + Tislelizumab Sitravatinib 80 mg orally once daily in 21-day cycles with tislelizumab 200 mg intravenously (IV) once every 3 weeks in participants with unresectable locally advanced or metastatic HCC or G/GEJ cancer | 3 |
| Sitravatinib 120 mg + Tislelizumab Sitravatinib 120 mg orally once daily in 21-day cycles with tislelizumab 200 mg IV once every 3 weeks in participants with unresectable locally advanced or metastatic HCC or G/GEJ cancer | 81 |
| Total | 111 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 0 | 12 | 2 | 53 |
| Overall Study | Lost to Follow-up | 1 | 2 | 0 | 0 |
| Overall Study | Sponsor Decision | 0 | 6 | 0 | 15 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 5 |
Baseline characteristics
| Characteristic | Sitravatinib 120 mg + Tislelizumab | Sitravatinib 80 mg + Tislelizumab | Sitravatinib Monotherapy: 120 mg | Sitravatinib Monotherapy: 80 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 56.4 Years STANDARD_DEVIATION 10.23 | 56.3 Years STANDARD_DEVIATION 6.51 | 53.3 Years STANDARD_DEVIATION 9.92 | 57.7 Years STANDARD_DEVIATION 10.02 | 55.7 Years STANDARD_DEVIATION 10.1 |
| Race/Ethnicity, Customized Asian: Chinese | 81 Participants | 3 Participants | 24 Participants | 3 Participants | 111 Participants |
| Sex: Female, Male Female | 10 Participants | 1 Participants | 2 Participants | 1 Participants | 14 Participants |
| Sex: Female, Male Male | 71 Participants | 2 Participants | 22 Participants | 2 Participants | 97 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 12 / 24 | 2 / 3 | 53 / 81 |
| other Total, other adverse events | 3 / 3 | 24 / 24 | 3 / 3 | 78 / 81 |
| serious Total, serious adverse events | 1 / 3 | 7 / 24 | 2 / 3 | 31 / 81 |
Outcome results
Primary
Number of Participants With Adverse Events
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0), including relevant physical examination, electrocardiograms, and laboratory assessments. Safety analysis set is presented by dose, as prespecified in the statistical analysis plan (SAP).
Time frame: Up to approximately 4 years and 1 month
Population: The Safety Analysis Set includes all participants who received ≥ 1 dose of any study drug
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sitravatinib Monotherapy: 80 mg | Number of Participants With Adverse Events | At least one TEAE | 3 Participants |
| Sitravatinib Monotherapy: 80 mg | Number of Participants With Adverse Events | At least one SAE | 1 Participants |
| Sitravatinib Monotherapy: 120 mg | Number of Participants With Adverse Events | At least one SAE | 7 Participants |
| Sitravatinib Monotherapy: 120 mg | Number of Participants With Adverse Events | At least one TEAE | 24 Participants |
| Sitravatinib 80 mg + Tislelizumab | Number of Participants With Adverse Events | At least one TEAE | 3 Participants |
| Sitravatinib 80 mg + Tislelizumab | Number of Participants With Adverse Events | At least one SAE | 2 Participants |
| Sitravatinib 120 mg + Tislelizumab | Number of Participants With Adverse Events | At least one TEAE | 78 Participants |
| Sitravatinib 120 mg + Tislelizumab | Number of Participants With Adverse Events | At least one SAE | 31 Participants |
Primary
Objective Response Rate (ORR)
ORR is defined as the percentage of participants whose best overall response (BOR) is the confirmed complete response (CR) or partial response (PR) assessed by investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Efficacy evaluable analysis set is presented by indication group, as prespecified in the statistical analysis plan.
Time frame: Up to approximately 4 years and 1 month
Population: The Efficacy Evaluable Analysis Set includes all participants who received ≥ 1 dose of any study drug with measurable disease at baseline per RECIST v1.1 and who had ≥ 1 evaluable postbaseline tumor assessment unless treatment was discontinued due to clinical progression or early death (within 13 weeks after the first dose date) before tumor assessment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sitravatinib Monotherapy: 80 mg | Objective Response Rate (ORR) | Anti-PD-1/PD-L1 naïve or R/R HCC | 25.0 Percentage of participants |
| Sitravatinib Monotherapy: 120 mg | Objective Response Rate (ORR) | Anti-PD-1/PD-L1 naïve HCC | 11.5 Percentage of participants |
| Sitravatinib Monotherapy: 120 mg | Objective Response Rate (ORR) | Anti-PD-1/PD-L1 R/R HCC | 9.5 Percentage of participants |
| Sitravatinib Monotherapy: 120 mg | Objective Response Rate (ORR) | Anti-PD-1/PD-L1 naïve G/GEJ cancer | 16.1 Percentage of participants |
Secondary
Area Under the Plasma Concentration-time Curve During the Dosing Interval (AUC(0-tau)) for Sitravatinib
Time frame: Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)
Population: The Sitravatinib PK Analysis Set includes all participants who contributed ≥ 1 quantifiable PK sample for sitravatinib
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Sitravatinib Monotherapy: 80 mg | Area Under the Plasma Concentration-time Curve During the Dosing Interval (AUC(0-tau)) for Sitravatinib | C1D1 | 535.82 h*ng/mL | — |
| Sitravatinib Monotherapy: 80 mg | Area Under the Plasma Concentration-time Curve During the Dosing Interval (AUC(0-tau)) for Sitravatinib | C1D21 | 1254.71 h*ng/mL | Geometric Coefficient of Variation 5.016 |
| Sitravatinib Monotherapy: 120 mg | Area Under the Plasma Concentration-time Curve During the Dosing Interval (AUC(0-tau)) for Sitravatinib | C1D1 | 686.11 h*ng/mL | Geometric Coefficient of Variation 122.918 |
| Sitravatinib 80 mg + Tislelizumab | Area Under the Plasma Concentration-time Curve During the Dosing Interval (AUC(0-tau)) for Sitravatinib | C1D21 | 2745.23 h*ng/mL | — |
| Sitravatinib 120 mg + Tislelizumab | Area Under the Plasma Concentration-time Curve During the Dosing Interval (AUC(0-tau)) for Sitravatinib | C1D1 | 639.49 h*ng/mL | Geometric Coefficient of Variation 63.908 |
| Sitravatinib 120 mg + Tislelizumab | Area Under the Plasma Concentration-time Curve During the Dosing Interval (AUC(0-tau)) for Sitravatinib | C1D21 | 1532.33 h*ng/mL | Geometric Coefficient of Variation 44.296 |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Time Point (AUC(0-t)) for Sitravatinib
Time frame: Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)
Population: The Sitravatinib PK Analysis Set includes all participants who contributed ≥ 1 quantifiable PK sample for sitravatinib
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Sitravatinib Monotherapy: 80 mg | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Time Point (AUC(0-t)) for Sitravatinib | C1D1 | 397.95 h*ng/mL | Geometric Coefficient of Variation 25.561 |
| Sitravatinib Monotherapy: 80 mg | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Time Point (AUC(0-t)) for Sitravatinib | C1D21 | 1276.52 h*ng/mL | Geometric Coefficient of Variation 3.498 |
| Sitravatinib Monotherapy: 120 mg | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Time Point (AUC(0-t)) for Sitravatinib | C1D21 | 1364.56 h*ng/mL | Geometric Coefficient of Variation 116.841 |
| Sitravatinib Monotherapy: 120 mg | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Time Point (AUC(0-t)) for Sitravatinib | C1D1 | 761.95 h*ng/mL | Geometric Coefficient of Variation 62.68 |
| Sitravatinib 80 mg + Tislelizumab | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Time Point (AUC(0-t)) for Sitravatinib | C1D1 | 604.63 h*ng/mL | Geometric Coefficient of Variation 118.143 |
| Sitravatinib 80 mg + Tislelizumab | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Time Point (AUC(0-t)) for Sitravatinib | C1D21 | 1095.90 h*ng/mL | Geometric Coefficient of Variation 119.358 |
| Sitravatinib 120 mg + Tislelizumab | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Time Point (AUC(0-t)) for Sitravatinib | C1D1 | 840.74 h*ng/mL | Geometric Coefficient of Variation 59.869 |
| Sitravatinib 120 mg + Tislelizumab | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Time Point (AUC(0-t)) for Sitravatinib | C1D21 | 1089.57 h*ng/mL | Geometric Coefficient of Variation 91.752 |
Secondary
Clearance After Oral Administration (CL/F) for Sitravatinib
Time frame: Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)
Population: The Sitravatinib PK Analysis Set includes all participants who contributed ≥ 1 quantifiable PK sample for sitravatinib
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Sitravatinib Monotherapy: 80 mg | Clearance After Oral Administration (CL/F) for Sitravatinib | C1D1 | 92.58 Liters/hour | — |
| Sitravatinib Monotherapy: 80 mg | Clearance After Oral Administration (CL/F) for Sitravatinib | C1D21 | 63.76 Liters/hour | Geometric Coefficient of Variation 5.016 |
| Sitravatinib Monotherapy: 120 mg | Clearance After Oral Administration (CL/F) for Sitravatinib | C1D1 | 35.23 Liters/hour | — |
| Sitravatinib 80 mg + Tislelizumab | Clearance After Oral Administration (CL/F) for Sitravatinib | C1D21 | 29.14 Liters/hour | — |
| Sitravatinib 120 mg + Tislelizumab | Clearance After Oral Administration (CL/F) for Sitravatinib | C1D1 | 82.77 Liters/hour | Geometric Coefficient of Variation 62.096 |
| Sitravatinib 120 mg + Tislelizumab | Clearance After Oral Administration (CL/F) for Sitravatinib | C1D21 | 78.31 Liters/hour | Geometric Coefficient of Variation 44.296 |
Secondary
Disease Control Rate (DCR)
DCR is defined as the percentage of participants with BOR as CR, PR, or stable disease (SD) assessed by investigator per RECIST v1.1. Efficacy evaluable analysis set is presented by indication group, as prespecified in the statistical analysis plan.
Time frame: Up to approximately 4 years and 1 month
Population: The Efficacy Evaluable Analysis Set includes all participants who received ≥ 1 dose of any study drug with measurable disease at baseline per RECIST v1.1 and who had ≥ 1 evaluable postbaseline tumor assessment unless treatment was discontinued due to clinical progression or early death (within 13 weeks after the first dose date) before tumor assessment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sitravatinib Monotherapy: 80 mg | Disease Control Rate (DCR) | Anti-PD-1/PD-L1 naïve or R/R HCC | 90.0 Percentage of participants |
| Sitravatinib Monotherapy: 120 mg | Disease Control Rate (DCR) | Anti-PD-1/PD-L1 naïve HCC | 84.6 Percentage of participants |
| Sitravatinib Monotherapy: 120 mg | Disease Control Rate (DCR) | Anti-PD-1/PD-L1 R/R HCC | 81.0 Percentage of participants |
| Sitravatinib Monotherapy: 120 mg | Disease Control Rate (DCR) | Anti-PD-1/PD-L1 naïve G/GEJ cancer | 71.0 Percentage of participants |
Secondary
Duration of Response (DOR)
DOR is defined as the time from the first determination of an objective response until the first documentation of progressive disease as assessed by investigator per RECIST v1.1, or death, whichever comes first. Results are reported for indication groups with responders, defined as complete response (CR) or partial response (PR). Efficacy evaluable analysis set is presented by indication group, as prespecified in the statistical analysis plan.
Time frame: Up to approximately 4 years and 1 month
Population: The Efficacy Evaluable Analysis Set includes all participants who received ≥ 1 dose of any study drug with measurable disease at baseline per RECIST v1.1 and who had ≥ 1 evaluable postbaseline tumor assessment unless treatment was discontinued due to clinical progression or early death (within 13 weeks after the first dose date) before tumor assessment
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sitravatinib Monotherapy: 80 mg | Duration of Response (DOR) | Anti-PD-1/PD-L1 naïve or R/R HCC | 7.7 Months |
| Sitravatinib Monotherapy: 120 mg | Duration of Response (DOR) | Anti-PD-1/PD-L1 naïve HCC | 5.7 Months |
| Sitravatinib Monotherapy: 120 mg | Duration of Response (DOR) | Anti-PD-1/PD-L1 R/R HCC | NA Months |
| Sitravatinib Monotherapy: 120 mg | Duration of Response (DOR) | Anti-PD-1/PD-L1 naïve G/GEJ cancer | 5.5 Months |
Secondary
Maximum Plasma Concentration (Cmax) for Sitravatinib
Time frame: Predose and up to 24 hours postdose on Cycle 1 Day 1 (C1D1) and Cycle 1 Day 21 (C1D21) (21 days in each cycle)
Population: The Sitravatinib Pharmacokinetic (PK) Analysis Set includes all participants who contributed ≥ 1 quantifiable PK sample for sitravatinib
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Sitravatinib Monotherapy: 80 mg | Maximum Plasma Concentration (Cmax) for Sitravatinib | C1D1 | 27.11 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 38.968 |
| Sitravatinib Monotherapy: 80 mg | Maximum Plasma Concentration (Cmax) for Sitravatinib | C1D21 | 63.98 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 3.06 |
| Sitravatinib Monotherapy: 120 mg | Maximum Plasma Concentration (Cmax) for Sitravatinib | C1D21 | 69.30 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 78.298 |
| Sitravatinib Monotherapy: 120 mg | Maximum Plasma Concentration (Cmax) for Sitravatinib | C1D1 | 45.47 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 67.213 |
| Sitravatinib 80 mg + Tislelizumab | Maximum Plasma Concentration (Cmax) for Sitravatinib | C1D1 | 37.02 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 94.99 |
| Sitravatinib 80 mg + Tislelizumab | Maximum Plasma Concentration (Cmax) for Sitravatinib | C1D21 | 56.01 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 103.431 |
| Sitravatinib 120 mg + Tislelizumab | Maximum Plasma Concentration (Cmax) for Sitravatinib | C1D1 | 51.07 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 52.218 |
| Sitravatinib 120 mg + Tislelizumab | Maximum Plasma Concentration (Cmax) for Sitravatinib | C1D21 | 62.38 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 54.927 |
Secondary
Observed Accumulation Ratio (Ro) for AUC(0-tau) for Sitravatinib
Time frame: Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)
Population: The Sitravatinib PK Analysis Set includes all participants who contributed ≥ 1 quantifiable PK sample for sitravatinib
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sitravatinib Monotherapy: 80 mg | Observed Accumulation Ratio (Ro) for AUC(0-tau) for Sitravatinib | NA Ratio |
| Sitravatinib 120 mg + Tislelizumab | Observed Accumulation Ratio (Ro) for AUC(0-tau) for Sitravatinib | 3.94 Ratio |
Secondary
Observed Accumulation Ratio (Ro) for Cmax for Sitravatinib
Time frame: Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)
Population: The Sitravatinib PK Analysis Set includes all participants who contributed ≥ 1 quantifiable PK sample for sitravatinib
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sitravatinib Monotherapy: 80 mg | Observed Accumulation Ratio (Ro) for Cmax for Sitravatinib | 2.36 Ratio |
| Sitravatinib Monotherapy: 120 mg | Observed Accumulation Ratio (Ro) for Cmax for Sitravatinib | 2.12 Ratio |
| Sitravatinib 80 mg + Tislelizumab | Observed Accumulation Ratio (Ro) for Cmax for Sitravatinib | 1.51 Ratio |
| Sitravatinib 120 mg + Tislelizumab | Observed Accumulation Ratio (Ro) for Cmax for Sitravatinib | 1.48 Ratio |
Secondary
Plasma Concentrations of Sitravatinib
Time frame: Predose and 6 hours postdose in Cycle 5 Day 1 (21 days in each cycle)
Population: The Sitravatinib PK Analysis Set includes all participants who contributed ≥ 1 quantifiable PK sample for sitravatinib
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Sitravatinib Monotherapy: 80 mg | Plasma Concentrations of Sitravatinib | Predose: Anti-PD-1/PD-L1 naïve or R/R HCC | 31.64 ng/mL | Geometric Coefficient of Variation 18.492 |
| Sitravatinib Monotherapy: 80 mg | Plasma Concentrations of Sitravatinib | Postdose: Anti-PD-1/PD-L1 naïve or R/R HCC | 48.12 ng/mL | Geometric Coefficient of Variation 34.581 |
| Sitravatinib Monotherapy: 120 mg | Plasma Concentrations of Sitravatinib | Predose: Anti-PD-1/PD-L1 naïve HCC | 23.54 ng/mL | Geometric Coefficient of Variation 1435.332 |
| Sitravatinib Monotherapy: 120 mg | Plasma Concentrations of Sitravatinib | Postdose: Anti-PD-1/PD-L1 naïve HCC | 77.40 ng/mL | Geometric Coefficient of Variation 65.582 |
| Sitravatinib Monotherapy: 120 mg | Plasma Concentrations of Sitravatinib | Predose: Anti-PD-1/PD-L1 R/R HCC | 35.95 ng/mL | Geometric Coefficient of Variation 91.411 |
| Sitravatinib Monotherapy: 120 mg | Plasma Concentrations of Sitravatinib | Postdose: Anti-PD-1/PD-L1 R/R HCC | 54.05 ng/mL | Geometric Coefficient of Variation 49.017 |
| Sitravatinib Monotherapy: 120 mg | Plasma Concentrations of Sitravatinib | Predose: Anti-PD-1/PD-L1 naïve G/GEJ cancer | 31.13 ng/mL | Geometric Coefficient of Variation 66.433 |
| Sitravatinib Monotherapy: 120 mg | Plasma Concentrations of Sitravatinib | Postdose: Anti-PD-1/PD-L1 naïve G/GEJ cancer | 42.22 ng/mL | Geometric Coefficient of Variation 32.131 |
Secondary
Progression-free Survival (PFS)
PFS is defined as the time from the date of first dose to the date of first documentation of progressive disease assessed by the investigator per RECIST v1.1 or death, whichever occurs first. Safety analysis set is presented by indication group, as prespecified in the statistical analysis plan.
Time frame: Up to approximately 4 years and 1 month
Population: The Safety Analysis Set includes all participants who received ≥ 1 dose of any study drug
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sitravatinib Monotherapy: 80 mg | Progression-free Survival (PFS) | Anti-PD-1/PD-L1 naïve or R/R HCC | 6.8 Months |
| Sitravatinib Monotherapy: 120 mg | Progression-free Survival (PFS) | Anti-PD-1/PD-L1 naïve HCC | 6.8 Months |
| Sitravatinib Monotherapy: 120 mg | Progression-free Survival (PFS) | Anti-PD-1/PD-L1 R/R HCC | 4.2 Months |
| Sitravatinib Monotherapy: 120 mg | Progression-free Survival (PFS) | Anti-PD-1/PD-L1 naïve G/GEJ cancer | 3.6 Months |
Secondary
Time to Maximum Plasma Concentration (Tmax) for Sitravatinib
Time frame: Predose and up to 24 hours postdose on C1D1 and C1D21 (21 days in each cycle)
Population: The Sitravatinib PK Analysis Set includes all participants who contributed ≥ 1 quantifiable PK sample for sitravatinib
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sitravatinib Monotherapy: 80 mg | Time to Maximum Plasma Concentration (Tmax) for Sitravatinib | C1D1 | 10.0 Hours (h) |
| Sitravatinib Monotherapy: 80 mg | Time to Maximum Plasma Concentration (Tmax) for Sitravatinib | C1D21 | 6.00 Hours (h) |
| Sitravatinib Monotherapy: 120 mg | Time to Maximum Plasma Concentration (Tmax) for Sitravatinib | C1D21 | 3.04 Hours (h) |
| Sitravatinib Monotherapy: 120 mg | Time to Maximum Plasma Concentration (Tmax) for Sitravatinib | C1D1 | 7.04 Hours (h) |
| Sitravatinib 80 mg + Tislelizumab | Time to Maximum Plasma Concentration (Tmax) for Sitravatinib | C1D1 | 10.0 Hours (h) |
| Sitravatinib 80 mg + Tislelizumab | Time to Maximum Plasma Concentration (Tmax) for Sitravatinib | C1D21 | 6.00 Hours (h) |
| Sitravatinib 120 mg + Tislelizumab | Time to Maximum Plasma Concentration (Tmax) for Sitravatinib | C1D1 | 7.58 Hours (h) |
| Sitravatinib 120 mg + Tislelizumab | Time to Maximum Plasma Concentration (Tmax) for Sitravatinib | C1D21 | 9.15 Hours (h) |