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

NCT04401800 | Completed Phase 2 Results DMC

• 2 other identifiers: BGB-A317-211CTR20200972
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 9

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.

Conditions

Hepatocellular Carcinoma; Unresectable Hepatocellular Carcinoma; Metastatic Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  Response was assessed every 6 weeks for the first year and approximately every 9 weeks thereafter through December 2022; up to 27 months

Secondary Outcomes (19)

• 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)

Study Arms (1)

Lenvatinib With Tislelizumab

EXPERIMENTAL

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.

Drug: Lenvatinib; Drug: Tislelizumab

Interventions

Lenvatinib DRUG

Capsules administered orally once daily

Lenvatinib With Tislelizumab

Tislelizumab DRUG

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

Lenvatinib With Tislelizumab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• BeiGene: lead

Study Sites (9)

Anhui Provincial Hospital

Hefei, Anhui, 230000, China

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

Sun Yat Sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, 510515, China

Location

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150000, China

Location

The First Affiliated Hospital of Xian Jiaotong University

Xi'an, Shaanxi, 710061, China

Location

Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200092, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

Location

Zhejiang University College of Medicine Second Affiliated Hospital

Hangzhou, Zhejiang, 310009, China

Location

Related Publications (1)

• Xu L, Chen J, Liu C, Song X, Zhang Y, Zhao H, Yan S, Jia W, Wu Z, Guo Y, Yang J, Gong W, Ma Y, Yang X, Gao Z, Zhang N, Zheng X, Li M, Su D, Chen M. Efficacy and safety of tislelizumab plus lenvatinib as first-line treatment in patients with unresectable hepatocellular carcinoma: a multicenter, single-arm, phase 2 trial. BMC Med. 2024 Apr 23;22(1):172. doi: 10.1186/s12916-024-03356-5.

  PMID: 38650037 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

lenvatinib; tislelizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Results Point of Contact

• Title: Study Director
• Organization: BeiGene

clinicaltrials@beigene.com

+1-877-828-5568

Study Officials

• Study Director

  BeiGene

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2020
• First Posted: May 26, 2020
• Study Start: September 4, 2020
• Primary Completion: December 1, 2022
• Study Completion: February 18, 2024
• Last Updated: March 10, 2025
• Results First Posted: March 10, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share

Locations

CN (9)