A Phase III Clinical Trial of AK105 Injection Combined With Anlotinib Hydrochloride Capsules Versus Sorafenib in Subjects With Advanced Hepatocellular Carcinoma (HCC)

A Randomized, Controlled, Open-label, Multicenter Phase III Clinical Trial of AK105 Injection Combined With Anlotinib Hydrochloride Capsules Versus Sorafenib in Subjects With Advanced Hepatocellular Carcinoma (HCC)

This is a randomized, controlled, open-label, multicenter study to evaluate efficacy of AK105 injection combined with Anlotinib Hydrochloride Capsules versus Sorafenib. Patients are treated with AK105 injection combined with Anlotinib Hydrochloride Capsules or Sorafenib, with 2:1 random ratio. Every 21 days is a treatment cycle.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Hepatocellular Carcinoma (HCC)
• Intervention / Treatment: Drug: AK105 Injection; Drug: Anlotinib Hydrochloride Capsules; Drug: Sorafenib Tosylate Tablets

• Study Type: Interventional
• Enrollment (Estimated): 648
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233004
      • The First Affiliated Hospital of Bengbu Medical College
    • Hefei, Anhui, China, 230001
      • Anhui Provincial Hospital
    • Hefei, Anhui, China, 230022
      • The First Affiliated Hospital of Anhui Medical University
    • Hefei, Anhui, China, 230031
      • Anhui Provincial Cancer Hospital
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital
    • Beijing, Beijing, China, 100853
      • Chinese PLA General Hospital
    • Beijing, Beijing, China, 102218
      • Beijing Tsinghua Changgung Hospital
    • Beijing, Beijing, China
      • Beijing Luhe Hospital.Capital Medical University
    • Beijing, Beijing, China, 100015
      • Beijing Ditan Hospital.Capital Medical University
    • Beijing, Beijing, China, 100069
      • Beijing YouAn Hospital.Capital Medical University
  • Chongqing
    • Chongqing, Chongqing, China, 400010
      • The Second Affiliated Hospital of Chongqing Medical University
    • Chongqing, Chongqing, China, 404031
      • Chongqing University Three Gorges Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Provincial Cancer Hospital
    • Fuzhou, Fujian, China, 350005
      • The First Affiliated Hospital of Fujian Medical University
    • Xiamen, Fujian, China, 361003
      • The first affiliated hospital of xiamen university
    • Xiamen, Fujian, China, 361004
      • Zhongshan Hospital Xiamen University
  • Gansu
    • Lanzhou, Gansu, China, 730000
      • The First Hospital of Lanzhou University
    • Lanzhou, Gansu, China, 730030
      • Lanzhou University Second Hospital
    • Wuwei, Gansu, China, 733000
      • Gansu Wuwei Tumour Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Provincial People's Hospital
    • Guangzhou, Guangdong, China, 510289
      • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
    • Guangzhou, Guangdong, China
      • The First Affiliated Hospital,Sun Yat-sen University
  • Guangxi
    • Nanning, Guangxi, China, 530031
      • The Second Nanning People's Hospital
  • Guangxi Zhuang Autonomous Region
    • Nanning, Guangxi Zhuang Autonomous Region, China, 530021
      • Guangxi Medical University Affiliated Tumor Hospital
    • Nanning, Guangxi Zhuang Autonomous Region, China, 530021
      • The First Affiliated Hospital of Guangxi Medical University
  • Guizhou
    • Guiyang, Guizhou, China, 550002
      • Guizhou Provincial People's Hospital
    • Guiyang, Guizhou, China, 550081
      • Cancer Hospital of Guizhou Medical University
    • Zunyi, Guizhou, China, 563099
      • Affiliated Hospital of Zunyi Medical University
  • Hainan
    • Haikou, Hainan, China, 570311
      • Hainan General Hospital
    • Haikou, Hainan, China, 570311
      • The Second Affiliated Hospital of Hainan Medical Universit
  • Hebei
    • Shijiazhuang, Hebei, China, 050051
      • The Third Hospital of Hebei Medical University
  • Hebie
    • Qinhuangdao, Hebie, China, 350014
      • First Hospital of Qinhuangdao
  • Heibei
    • Chengde, Heibei, China, 67020
      • Affiliated Hospital of Chengde Medical University
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Affiliated Tumor Hospital of Harbin Medical University
  • Henan
    • Luoyang, Henan, China, 471003
      • The first affiliated hospital of Henan University of science and technology
    • Nanyang, Henan, China, 473006
      • Nanyang First People's Hospita
    • Sanmenxia, Henan, China, 472000
      • Sanmenxia Central Hospital
    • Xinxiang, Henan, China, 453000
      • Xinxiang Central Hospital
    • Zhengzhou, Henan, China, 450052
      • The first affiliated hospital of Zhengzhou university
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430071
      • Zhongnan Hospital of Wuhan University
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital Central South University
    • Changsha, Hunan, China, 410013
      • The Third Xiangya Hospital of Central South University
    • Changsha, Hunan, China, 410013
      • Hunan Cancar Hospital
    • Changsha, Hunan, China, 410021
      • Hunan Provincial People's Hospital
    • Changsha, Hunan, China, 410205
      • Hunan Cancer Hospital(Department II of Gastroenterology and Urology/Hepatobiliary Surgery)
  • Jiangsu
    • Nanjing, Jiangsu, China, 210003
      • The Second Hospital of Nanjing
    • Nanjing, Jiangsu, China, 210000
      • The First Affiliated Hospital of Nanjing Medical University
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Cancer Hospital
    • Nantong, Jiangsu, China, 226361
      • Nantong Tumor Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of NanChang University
  • Jilin
    • Changchun, Jilin, China, 13000
      • Jilin Cancer Hospital
    • Changchun, Jilin, China, 130021
      • The First Hospital Affiliated to Jilin Universit
    • Changchun, Jilin, China, 130700
      • Jilin Guowen Hospital
  • Lanzhou
    • Gansu, Lanzhou, China, 730099
      • Gansu Provincial Hospital
  • Liaoning
    • Jinzhou, Liaoning, China, 121012
      • The First Affiliated Hospital of Jinzhou Medical University
    • Shenyang, Liaoning, China, 110042
      • Liaoning Cancer Hospital
    • Shenyang, Liaoning, China, 110006
      • The Sixth People's Hospital of Shenyang
  • Shaanxi
    • Baoji, Shaanxi, China, 721000
      • Baoji Central Hospital
    • Hanzhong, Shaanxi, China, 723000
      • Hanzhong Central Hospital
  • Shandong
    • Jinan, Shandong, China, 250012
      • Qilu Hospital of Shandong University
    • Liaocheng, Shandong, China, 252004
      • Liaocheng People's Hospital
    • Weifang, Shandong, China, 262550
      • Yidu Central Hospital of Weifang
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital, Fuadn University
    • Shanghai, Shanghai, China, 201800
      • The Third Affiliated Hospital of the Second Military Medical University of the Chinese people's Liberation Army
  • Shanxi
    • Taiyuan, Shanxi, China, 030013
      • Shanxi Provinaial Cancer Hospital
    • Xi'an, Shanxi, China, 710061
      • First Affiliated Hospital of Xi'an JiaoTong University
    • Xi'an, Shanxi, China, 710038
      • Tangdu Hospital of the Fourth Military Medical University of the People's Liberation Army of China
    • Xi'an, Shanxi, China, 710061
      • Shanxi Provincial Cancer hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610081
      • Affiliated Hospital Of ChengDu University
    • Chengdu, Sichuan, China, 610042
      • Sichuan Cancer Hospital
    • Nanchong, Sichuan, China, 637000
      • Affiliated Hospital of North Sichuan Medical College
  • Tianjin
    • Tianjin, Tianjin, China, 300170
      • Tianjin Third Central Hospital
    • Tianjin, Tianjin, China, 300192
      • Tianjin Second People's Hospital
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancar institute & Hospital
  • Xinjiang Uygur Autonomous Region
    • Ürümqi, Xinjiang Uygur Autonomous Region, China, 830054
      • The first affiliated hospital of Xinjiang medical university
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310015
      • Shulan (Hangzhou) Hospital
    • Wenzhou, Zhejiang, China, 325000
      • The First Affiliated Hospital of Wenzhou Medical University
    • Wenzhou, Zhejiang, China, 325041
      • Wenzhou People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. 18-75 years old; Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; Life expectancy ≥ 3 months.

  2. Histopathology or cytology confirmed as HCC. 3. Has not received any systematic treatment for HCC. 4. Stage B or C in the Barcelona Clinic Liver Cancer (BCLC) classification, and is not suitable for surgery or local treatment, or progress after surgery or local treatment.

  5. Child-Pugh liver function classification : A or B (≤7 points). 6. Central nervous system metastasis has no clinical symptoms or is stable at least 4 weeks after treatment.

  7. Quantification of HBV DNA <500IU/ml or 2500 Copys/ml, and anti-HBV therapy should be given for at least 2 weeks before the first administration; Quantification of HCV RNA is positive must complete antiviral therapy at least 1 month before the first administration.

  8. Patients who progress after local treatment should be at least 4 weeks after the end of local treatment.

  9. Radiotherapy for bone metastases accompanied by clinical symptoms must be completed at least 2 weeks before the first administration.

  10. Has at least one measurable lesion. 11. Adequate organ function. 12. Male or female subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study (such as intrauterine devices , contraceptives or condoms) ；No pregnant or breastfeeding women, and a negative pregnancy test are received within 7 days before the randomization.

  13.Understood and signed an informed consent form.

Exclusion Criteria:

• 1. Histopathology or cytology confirmed as fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, hepatobiliary cell carcinoma, mixed liver cancer, etc.

  2. Has used anti-angiogenic drugs such as anlotinib, apatinib, lenvatinib, sorafenib, sunitinib, bevacizumab, or related immunotherapy drugs for PD-1, PD-L1, etc.

  3. Has received systemic treatment such as chemotherapy and biological therapy. 4. Has a history of hepatic encephalopathy. 5. According to imaging examination, the portal vein has invasion of cancer embolus, inferior vena cava or heart involvement.

  6. Hepatitis B with hepatitis C or hepatitis D infection. 7. Has received or planned to receive organ transplantation. 8. Has other malignant tumors within 5 years. 9. Has multiple factors affecting oral medication. 10. Has uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.

  11. Has any bleeding or bleeding events ≥grade 3 in the first 4 weeks before the first administration.

  12. Has unhealed wounds, fractures, active gastric and duodenal ulcers, positive continuous fecal occult blood, ulcerative colitis in the first 4 weeks before the first administration.

  13. Has adverse events caused by previous therapy except alopecia that did not recover to ≤grade 1.

  14. Has received surgery, or unhealed wounds within 4 weeks before the first administration.

  15. Has drug abuse history that unable to abstain from or mental disorders. 16. Has any serious and / or uncontrolled disease. 17. Has received vaccination or attenuated vaccine within 4 weeks prior to the first administration.

  18. Has received anti-tumor Traditional Chinese Medicine within 2 weeks before the first administration.

  19. Severe hypersensitivity after administration of other monoclonal antibodies.

  20. Has any active autoimmune disease or history of autoimmune disease. 21.Immunosuppressant or systemic or absorbable local hormone therapy is required to achieve the aim of immunosuppression (dose > 10mg/ day prednisone or other therapeutic hormones) and is still used within 2 weeks after the first administration.

  22.Has participated in other anticancer drug clinical trials within 4 weeks. 23.Portal hypertension with high risk of hemorrhage, or have red sign confirmed by gastroscopy.

  24.According to the judgement of the investigators, there are other factors that may lead to the termination of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AK105 combined with Anlotinib; AK105 200mg intravenously (IV) on day 1 of each 21-day cycle plus Anlotinib capsules 10mg given orally in fasting conditions , once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21).	Drug: AK105 Injection; AK105 200mg intravenously (IV) on day 1 of each 21-day cycle.; Drug: Anlotinib Hydrochloride Capsules; Anlotinib capsules 10mg given orally in fasting conditions , once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21).
Active Comparator: Sorafenib Tosylate Tablets; Sorafenib Tosylate Tablets 400mg given orally, twice daily in 21-day cycle.	Drug: Sorafenib Tosylate Tablets; Sorafenib Tosylate Tablets 400mg given orally, twice daily in 21-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	OS defined as the time from the first dose to death from any cause. Subjects who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive.	Up to 96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause.	Up to 96 weeks
Overall response rate（ORR）	Percentage of subjects achieving complete response (CR) and partial response (PR).	Up to 96 weeks
Disease control rate（DCR）	Percentage of subjects achieving complete response (CR) and partial response (PR) and stable disease (SD).	Up to 96 weeks
Duration of Response (DOR)	DOR defined as time from earliest date of disease response to earliest date of disease progression based on radiographic assessment.	Up to 96 weeks

Collaborators and Investigators

• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2020
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 10, 2020
• First Submitted That Met QC Criteria: April 10, 2020
• First Posted (Actual): April 14, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 18, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: ALTN-AK105-III-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No