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Completed

NCT Number: NCT04401800

Preliminary Antitumor Activity, Safety and Tolerability of Tislelizumab in Combination With Lenvatinib for Hepatocellular Carcinoma

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.

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Key information

Conditions

Hepatocellular Carcinoma Adenocarcinoma Carcinoma Carcinoma, Hepatocellular Digestive System Diseases Digestive System Neoplasms Liver Diseases Liver Neoplasms Metastatic Hepatocellular Carcinoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Unresectable Hepatocellular Carcinoma

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Anhui Provincial Hospital, Hefei, Anhui, China

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key 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

Key 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.

Treatment and study plan

Lenvatinib

Drug

Capsules administered orally once daily

Tislelizumab

Drug

200 mg intravenous (IV) infusion administered on Day 1 of each cycle

Primary outcomes

  1. 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

  1. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and TEAEs Leading to Treatment Discontinuation and Modification

    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)

    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.

  2. Objective Response Rate (ORR) as Assessed by the Investigator 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; 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.

  3. Objective Response Rate (ORR) as Assessed by the Investigator and Central Site Imaging Facility Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST)

    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 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.

  4. 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)

    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 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.

  5. Duration of Response (DOR) As Assessed by The Investigator Based on RECIST v1.1

    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)

    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.

  6. Duration of Response (DOR) As Assessed by The Central Site Imaging Facility Based on RECIST v1.1

    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)

    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.

  7. Duration of Response (DOR) As Assessed by The Investigator Based on mRECIST

    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)

    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.

  8. Duration of Response (DOR) As Assessed by the Central Site Imaging Facility Based on mRECIST

    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)

    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.

  9. Duration of Response (DOR) As Assessed by The Investigator Based on iRECIST

    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)

    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.

  10. Duration of Response (DOR) As Assessed by The Central Site Imaging Facility Based on iRECIST

    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)

    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.

  11. Disease Control Rate (DCR) As Assessed by The Investigator and Central Site 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

    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.

  12. Disease Control Rate (DCR) As Assessed by The Investigator and Central Site Imaging Facility Based on mRECIST

    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

    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.

  13. Disease Control Rate (DCR) As Assessed by The Investigator and Central Site Imaging Facility Based on iRECIST

    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

    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.

  14. Progression Free Survival (PFS) As Assessed by The Investigator Based on RECIST v1.1

    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)

    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.

  15. Progression Free Survival (PFS) As Assessed by The Central Site Imaging Facility Based on RECIST v1.1

    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)

    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.

  16. Progression Free Survival (PFS) As Assessed by The Investigator Based on mRECIST

    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)

    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.

  17. Progression Free Survival (PFS) As Assessed by The Central Site Imaging Facility Based on mRECIST

    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)

    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.

  18. Progression Free Survival (PFS) As Assessed by The Investigator Based on iRECIST

    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)

    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.

  19. Progression Free Survival (PFS) As Assessed by The Central Site Imaging Facility Based on iRECIST

    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)

    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.

Sponsors and collaborators

Lead sponsor

BeiGene

Industry

Registry information

Official study title

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

Important dates

Study start
2020
Primary completion
2022
Study completion
2024
First posted
May 26, 2020
Registry last updated
Mar 10, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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