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)
1 other identifier
interventional
648
1 country
81
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Aug 2020
Longer than P75 for phase_3
81 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 10, 2020
CompletedFirst Posted
Study publicly available on registry
April 14, 2020
CompletedStudy Start
First participant enrolled
August 11, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2026
February 20, 2025
November 1, 2024
6.3 years
April 10, 2020
February 18, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
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 Outcomes (4)
Progression-free survival (PFS)
Up to 96 weeks
Overall response rate（ORR）
Up to 96 weeks
Disease control rate（DCR）
Up to 96 weeks
Duration of Response (DOR)
Up to 96 weeks
Study Arms (2)
AK105 combined with Anlotinib
EXPERIMENTALAK105 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).
Sorafenib Tosylate Tablets
ACTIVE COMPARATORSorafenib Tosylate Tablets 400mg given orally, twice daily in 21-day cycle.
Interventions
AK105 200mg intravenously (IV) on day 1 of each 21-day cycle.
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).
Sorafenib Tosylate Tablets 400mg given orally, twice daily in 21-day cycle.
Eligibility Criteria
You may qualify if:
- \. 18-75 years old; Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; Life expectancy ≥ 3 months.
- \. 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.
- \. 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.
- \. 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.
- \. Patients who progress after local treatment should be at least 4 weeks after the end of local treatment.
- \. Radiotherapy for bone metastases accompanied by clinical symptoms must be completed at least 2 weeks before the first administration.
- \. 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.
- Understood and signed an informed consent form.
You may not qualify if:
- \. Histopathology or cytology confirmed as fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, hepatobiliary cell carcinoma, mixed liver cancer, etc.
- \. Has used anti-angiogenic drugs such as anlotinib, apatinib, lenvatinib, sorafenib, sunitinib, bevacizumab, or related immunotherapy drugs for PD-1, PD-L1, etc.
- \. 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.
- \. 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.
- \. Has any bleeding or bleeding events ≥grade 3 in the first 4 weeks before the first administration.
- \. 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.
- \. Has adverse events caused by previous therapy except alopecia that did not recover to ≤grade 1.
- \. Has received surgery, or unhealed wounds within 4 weeks before the first administration.
- \. 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.
- \. Has received anti-tumor Traditional Chinese Medicine within 2 weeks before the first administration.
- \. Severe hypersensitivity after administration of other monoclonal antibodies.
- \. 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.
- 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.
- According to the judgement of the investigators, there are other factors that may lead to the termination of the study.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (81)
The First Affiliated Hospital of Bengbu Medical College
Bengbu, Anhui, 233004, China
Anhui Provincial Hospital
Hefei, Anhui, 230001, China
The First Affiliated Hospital of Anhui Medical University
Hefei, Anhui, 230022, China
Anhui Provincial Cancer Hospital
Hefei, Anhui, 230031, China
Beijing Ditan Hospital.Capital Medical University
Beijing, Beijing Municipality, 100015, China
Beijing YouAn Hospital.Capital Medical University
Beijing, Beijing Municipality, 100069, China
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100730, China
Chinese Pla General Hospital
Beijing, Beijing Municipality, 100853, China
Beijing Tsinghua Changgung Hospital
Beijing, Beijing Municipality, 102218, China
Beijing Luhe Hospital.Capital Medical University
Beijing, Beijing Municipality, China
The Second Affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing Municipality, 400010, China
Chongqing University Three Gorges Hospital
Chongqing, Chongqing Municipality, 404031, China
The First Affiliated Hospital of Fujian Medical University
Fuzhou, Fujian, 350005, China
Fujian Provincial Cancer Hospital
Fuzhou, Fujian, 350014, China
The First Affiliated Hospital of Xiamen University
Xiamen, Fujian, 361003, China
Zhongshan Hospital Xiamen University
Xiamen, Fujian, 361004, China
The first hospital of Lanzhou University
Lanzhou, Gansu, 730000, China
Lanzhou University Second Hospital
Lanzhou, Gansu, 730030, China
Gansu Wuwei Tumour Hospital
Wuwei, Gansu, 733000, China
Guangdong Provincial People's Hospital
Guangzhou, Guangdong, 510080, China
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Guangzhou, Guangdong, 510289, China
The First Affiliated Hospital，Sun Yat-sen University
Guangzhou, Guangdong, China
Guangxi Medical University Affiliated Tumor Hospital
Nanning, Guangxi, 530021, China
The First Affiliated Hospital of Guangxi Medical University
Nanning, Guangxi, 530021, China
The Second Nanning People's Hospital
Nanning, Guangxi, 530031, China
Guizhou Provincial People's Hospital
Guiyang, Guizhou, 550002, China
Cancer Hospital of Guizhou Medical University
Guiyang, Guizhou, 550081, China
Affiliated Hospital of Zunyi Medical University
Zunyi, Guizhou, 563099, China
Hainan General Hospital
Haikou, Hainan, 570311, China
The Second Affiliated Hospital of Hainan Medical Universit
Haikou, Hainan, 570311, China
The Third Hospital of Hebei Medical University
Shijiazhuang, Hebei, 050051, China
First Hospital Of Qinhuangdao
Qinhuangdao, Hebie, 350014, China
Affiliated Hospital of Chengde Medical University
Chengde, Heibei, 67020, China
Affiliated Tumor Hospital of Harbin Medical University
Harbin, Heilongjiang, 150081, China
The First Affiliated Hospital of Henan University of Science and Technology
Luoyang, Henan, 471003, China
Nanyang First People's Hospita
Nanyang, Henan, 473006, China
Sanmenxia Central Hospital
Sanmenxia, Henan, 472000, China
Xinxiang central hospital
Xinxiang, Henan, 453000, China
Henan Cancer Hospital
Zhengzhou, Henan, 450008, China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 450052, China
Zhongnan Hospital of Wuhan University
Wuhan, Hubei, 430071, China
Hubei Cancer Hospital
Wuhan, Hubei, 430079, China
Xiangya Hospital Central South University
Changsha, Hunan, 410008, China
Hunan Cancar Hospital
Changsha, Hunan, 410013, China
The Third Xiangya Hospital of Central South University
Changsha, Hunan, 410013, China
Hunan Provincial People's Hospital
Changsha, Hunan, 410021, China
Hunan Cancer Hospital(Department II of Gastroenterology and Urology/Hepatobiliary Surgery)
Changsha, Hunan, 410205, China
The First Affiliated Hospital of Nanjing Medical University
Nanjing, Jiangsu, 210000, China
The Second Hospital of Nanjing
Nanjing, Jiangsu, 210003, China
Jiangsu Cancer Hospital
Nanjing, Jiangsu, 210029, China
Nantong Tumor Hospital
Nantong, Jiangsu, 226361, China
The First Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, 330006, China
Jilin Cancer Hospital
Changchun, Jilin, 13000, China
The First Hospital Affiliated to Jilin Universit
Changchun, Jilin, 130021, China
Jilin Guowen Hospital
Changchun, Jilin, 130700, China
Gansu Provincial Hospital
Gansu, Lanzhou, 730099, China
The First Affiliated Hospital of Jinzhou Medical University
Jinzhou, Liaoning, 121012, China
The Sixth People's Hospital Of Shenyang
Shenyang, Liaoning, 110006, China
Liaoning Cancer Hospital
Shenyang, Liaoning, 110042, China
Baoji Central Hospital
Baoji, Shaanxi, 721000, China
Hanzhong Central Hospital
Hanzhong, Shaanxi, 723000, China
Qilu Hospital of Shandong University
Jinan, Shandong, 250012, China
Liaocheng people's Hospital
Liaocheng, Shandong, 252004, China
Yidu Central Hospital Of Weifang
Weifang, Shandong, 262550, China
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 200032, China
Zhongshan Hospital, Fuadn University
Shanghai, Shanghai Municipality, 200032, China
The Third Affiliated Hospital of the Second Military Medical University of the Chinese people's Liberation Army
Shanghai, Shanghai Municipality, 201800, China
Shanxi Provinaial Cancer Hospital
Taiyuan, Shanxi, 030013, China
Tangdu Hospital of the Fourth Military Medical University of the People's Liberation Army of China
Xi’an, Shanxi, 710038, China
First Affiliated Hospital of Xi'an Jiaotong University
Xi’an, Shanxi, 710061, China
Shanxi Provincial Cancer Hospital
Xi’an, Shanxi, 710061, China
Sichuan Cancer Hospital
Chengdu, Sichuan, 610042, China
Affiliated Hospital of Chengdu University
Chengdu, Sichuan, 610081, China
Affiliated Hospital of North Sichuan Medical College
Nanchong, Sichuan, 637000, China
Tianjin Medical University Cancar institute & Hospital
Tianjin, Tianjin Municipality, 300060, China
Tianjin Third Central Hospital
Tianjin, Tianjin Municipality, 300170, China
Tianjin Second People's Hospital
Tianjin, Tianjin Municipality, 300192, China
The First Affiliated Hospital of Xinjiang Medical University
Ürümqi, Xinjiang Uygur Autonomous Region, 830054, China
Shulan (Hangzhou) hospital
Hangzhou, Zhejiang, 310015, China
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang, 325000, China
Wenzhou People's Hospital
Wenzhou, Zhejiang, 325041, China
Related Publications (1)
Zhou J, Bai L, Luo J, Bai Y, Pan Y, Yang X, Gao Y, Shi R, Zhang W, Zheng J, Hua X, Xu A, Hu S, Zhang F, Yang X, Da M, Wang R, Ma J, Jia W, Quan D, Peng C, Yang W, Yin G, Qi Y, Zhang G, Du X, Mao X, Meng Z, Jiao S, Fan J; APOLLO Study Group. Anlotinib plus penpulimab versus sorafenib in the first-line treatment of unresectable hepatocellular carcinoma (APOLLO): a randomised, controlled, phase 3 trial. Lancet Oncol. 2025 Jun;26(6):719-731. doi: 10.1016/S1470-2045(25)00190-1. Epub 2025 May 8.
PMID: 40349716DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 10, 2020
First Posted
April 14, 2020
Study Start
August 11, 2020
Primary Completion (Estimated)
December 1, 2026
Study Completion (Estimated)
December 1, 2026
Last Updated
February 20, 2025
Record last verified: 2024-11