A Phase 2 Study to Investigate the Preliminary Antitumor Activity, Safety and Tolerability of Tislelizumab in Combination With Lenvatinib in Patients With Unresectable Locally Advanced or Metastatic Hepatocellular Carcinoma

BeiGene9 sites in 1 country64 target enrollmentSeptember 4, 2020

ConditionsHepatocellular Carcinoma Unresectable Hepatocellular Carcinoma Metastatic Hepatocellular Carcinoma

InterventionsLenvatinib Tislelizumab

DrugsLenvatinib Tislelizumab

Overview

Phase: Phase 2
Intervention: Lenvatinib
Conditions: Hepatocellular Carcinoma
Sponsor: BeiGene
Enrollment: 64
Locations: 9
Primary Endpoint: Overall Response Rate (ORR) as Assessed by Central Imaging Facility Based on RECIST v1.1
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

September 4, 2020

End Date

February 18, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

BeiGene

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments
•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.
•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
•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
•At least 1 measurable lesion as defined by RECIST v1.1
•European Cancer Oncology Group (ECOG) Performance Status ≤ 1
•Child-Pugh A classification for liver function assessed within 7 days of first dose of study drugs

Exclusion Criteria

•Active autoimmune diseases or history of autoimmune diseases that may relapse
•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)
•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
•Any known brain or leptomeningeal metastases
•Concurrent participation in another therapeutic clinical study
•NOT: Other protocol defined Inclusion/Exclusion criteria may apply NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Arms & Interventions

Lenvatinib With Tislelizumab

Participants received lenvatinib based on baseline weight (12 milligrams \[mg\] or 8 mg once daily for participants with a baseline weight of \>= 60 kilograms \[kg\] 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.

Intervention: Lenvatinib

Lenvatinib With Tislelizumab

Intervention: Tislelizumab

Outcomes

Primary Outcomes

Overall Response Rate (ORR) as Assessed by Central Imaging Facility Based on RECIST v1.1

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

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 Outcomes

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))
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)
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)
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)
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))
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))
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))
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))
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))
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))
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)
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)
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)
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))
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))
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))
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))
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))
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))