A Phase III Clinical Trial of AK105 Injection Combined With Anlotinib Hydrochloride Capsules Versus Sorafenib in Subjects With Advanced Hepatocellular Carcinoma (HCC)
- Conditions
- Advanced Hepatocellular Carcinoma (HCC)
- Interventions
- Registration Number
- NCT04344158
- Lead Sponsor
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 648
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18-75 years old; Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; Life expectancy ≥ 3 months.
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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.
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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.
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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.
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Patients who progress after local treatment should be at least 4 weeks after the end of local treatment.
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Radiotherapy for bone metastases accompanied by clinical symptoms must be completed at least 2 weeks before the first administration.
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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.
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Histopathology or cytology confirmed as fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, hepatobiliary cell carcinoma, mixed liver cancer, etc.
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Has used anti-angiogenic drugs such as anlotinib, apatinib, lenvatinib, sorafenib, sunitinib, bevacizumab, or related immunotherapy drugs for PD-1, PD-L1, etc.
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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.
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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.
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Has any bleeding or bleeding events ≥grade 3 in the first 4 weeks before the first administration.
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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.
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Has adverse events caused by previous therapy except alopecia that did not recover to ≤grade 1.
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Has received surgery, or unhealed wounds within 4 weeks before the first administration.
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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.
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Has received anti-tumor Traditional Chinese Medicine within 2 weeks before the first administration.
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Severe hypersensitivity after administration of other monoclonal antibodies.
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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.
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AK105 combined with Anlotinib AK105 Injection 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). Sorafenib Tosylate Tablets Sorafenib Tosylate Tablets Sorafenib Tosylate Tablets 400mg given orally, twice daily in 21-day cycle. AK105 combined with Anlotinib Anlotinib Hydrochloride Capsules 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).
- Primary Outcome Measures
Name Time Method Overall survival (OS) Up to 96 weeks 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.
- Secondary Outcome Measures
Name Time Method Disease control rate（DCR） Up to 96 weeks Percentage of subjects achieving complete response (CR) and partial response (PR) and stable disease (SD).
Duration of Response (DOR) Up to 96 weeks DOR defined as time from earliest date of disease response to earliest date of disease progression based on radiographic assessment.
Progression-free survival (PFS) Up to 96 weeks PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause.
Overall response rate（ORR） Up to 96 weeks Percentage of subjects achieving complete response (CR) and partial response (PR).
Trial Locations
- Locations (81)
The First Affiliated Hospital of Nanjing Medical University
🇨🇳Nanjing, Jiangsu, China
The Second Hospital of Nanjing
🇨🇳Nanjing, Jiangsu, China
Shanxi Provinaial Cancer Hospital
🇨🇳Taiyuan, Shanxi, China
Tangdu Hospital of the Fourth Military Medical University of the People's Liberation Army of China
🇨🇳Xi'an, Shanxi, China
Wenzhou People's Hospital
🇨🇳Wenzhou, Zhejiang, China
Lanzhou University Second Hospital
🇨🇳Lanzhou, Gansu, China
The First Affiliated Hospital of Bengbu Medical College
🇨🇳Bengbu, Anhui, China
Anhui Provincial Hospital
🇨🇳Hefei, Anhui, China
The First Affiliated Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
Anhui Provincial Cancer Hospital
🇨🇳Hefei, Anhui, China
Beijing Ditan Hospital.Capital Medical University
🇨🇳Beijing, Beijing, China
Beijing YouAn Hospital.Capital Medical University
🇨🇳Beijing, Beijing, China
Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, China
Chinese Pla General Hospital
🇨🇳Beijing, Beijing, China
Beijing Tsinghua Changgung Hospital
🇨🇳Beijing, Beijing, China
Beijing Luhe Hospital.Capital Medical University
🇨🇳Beijing, Beijing, China
The Second Affiliated Hospital of Chongqing Medical University
🇨🇳Chongqing, Chongqing, China
Chongqing University Three Gorges Hospital
🇨🇳Chongqing, Chongqing, China
The First Affiliated Hospital of Fujian Medical University
🇨🇳Fuzhou, Fujian, China
Fujian Provincial Cancer Hospital
🇨🇳Fuzhou, Fujian, China
The First Affiliated Hospital of Xiamen University
🇨🇳Xiamen, Fujian, China
Zhongshan Hospital Xiamen University
🇨🇳Xiamen, Fujian, China
The first hospital of Lanzhou University
🇨🇳Lanzhou, Gansu, China
Gansu Wuwei Tumour Hospital
🇨🇳Wuwei, Gansu, China
Guangdong Provincial People's Hospital
🇨🇳Guangzhou, Guangdong, China
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital，Sun Yat-sen University
🇨🇳Guangzhou, Guangdong, China
Guangxi Medical University Affiliated Tumor Hospital
🇨🇳Nanning, Guangxi Zhuang Autonomous Region, China
The First Affiliated Hospital of Guangxi Medical University
🇨🇳Nanning, Guangxi Zhuang Autonomous Region, China
The Second Nanning People's Hospital
🇨🇳Nanning, Guangxi, China
Guizhou Provincial People's Hospital
🇨🇳Guiyang, Guizhou, China
Cancer Hospital of Guizhou Medical University
🇨🇳Guiyang, Guizhou, China
Affiliated Hospital of Zunyi Medical University
🇨🇳Zunyi, Guizhou, China
Hainan General Hospital
🇨🇳Haikou, Hainan, China
The Second Affiliated Hospital of Hainan Medical Universit
🇨🇳Haikou, Hainan, China
The Third Hospital of Hebei Medical University
🇨🇳Shijiazhuang, Hebei, China
First Hospital Of Qinhuangdao
🇨🇳Qinhuangdao, Hebie, China
Affiliated Hospital of Chengde Medical University
🇨🇳Chengde, Heibei, China
Affiliated Tumor Hospital of Harbin Medical University
🇨🇳Harbin, Heilongjiang, China
The First Affiliated Hospital of Henan University of Science and Technology
🇨🇳Luoyang, Henan, China
Nanyang First People's Hospita
🇨🇳Nanyang, Henan, China
Sanmenxia Central Hospital
🇨🇳Sanmenxia, Henan, China
Xinxiang central hospital
🇨🇳Xinxiang, Henan, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
Zhongnan Hospital of Wuhan University
🇨🇳Wuhan, Hubei, China
Hubei Cancer Hospital
🇨🇳Wuhan, Hubei, China
Shulan (Hangzhou) hospital
🇨🇳Hangzhou, Zhejiang, China
Xiangya Hospital Central South University
🇨🇳Changsha, Hunan, China
Hunan Cancar Hospital
🇨🇳Changsha, Hunan, China
The Third Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
Hunan Provincial People's Hospital
🇨🇳Changsha, Hunan, China
Hunan Cancer Hospital(Department II of Gastroenterology and Urology/Hepatobiliary Surgery)
🇨🇳Changsha, Hunan, China
Jiangsu Cancer Hospital
🇨🇳Nanjing, Jiangsu, China
Nantong Tumor Hospital
🇨🇳Nantong, Jiangsu, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Jilin Cancer Hospital
🇨🇳Changchun, Jilin, China
The First Hospital Affiliated to Jilin Universit
🇨🇳Changchun, Jilin, China
Jilin Guowen Hospital
🇨🇳Changchun, Jilin, China
Gansu Provincial Hospital
🇨🇳Gansu, Lanzhou, China
The First Affiliated Hospital of Jinzhou Medical University
🇨🇳Jinzhou, Liaoning, China
The Sixth People's Hospital Of Shenyang
🇨🇳Shenyang, Liaoning, China
Liaoning Cancer Hospital
🇨🇳Shenyang, Liaoning, China
Baoji Central Hospital
🇨🇳Baoji, Shaanxi, China
Hanzhong Central Hospital
🇨🇳Hanzhong, Shaanxi, China
Qilu Hospital of Shandong University
🇨🇳Jinan, Shandong, China
Liaocheng people's Hospital
🇨🇳Liaocheng, Shandong, China
Yidu Central Hospital Of Weifang
🇨🇳Weifang, Shandong, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Shanghai, China
Zhongshan Hospital, Fuadn University
🇨🇳Shanghai, Shanghai, China
The Third Affiliated Hospital of the Second Military Medical University of the Chinese people's Liberation Army
🇨🇳Shanghai, Shanghai, China
First Affiliated Hospital of Xi'an Jiaotong University
🇨🇳Xi'an, Shanxi, China
Shanxi Provincial Cancer Hospital
🇨🇳Xi'an, Shanxi, China
Sichuan Cancer Hospital
🇨🇳Chengdu, Sichuan, China
Affiliated Hospital of Chengdu University
🇨🇳Chengdu, Sichuan, China
Affiliated Hospital of North Sichuan Medical College
🇨🇳Nanchong, Sichuan, China
Tianjin Medical University Cancar institute & Hospital
🇨🇳Tianjin, Tianjin, China
Tianjin Third Central Hospital
🇨🇳Tianjin, Tianjin, China
Tianjin Second People's Hospital
🇨🇳Tianjin, Tianjin, China
The First Affiliated Hospital of Xinjiang Medical University
🇨🇳Ürümqi, Xinjiang Uygur Autonomous Region, China
The First Affiliated Hospital of Wenzhou Medical University
🇨🇳Wenzhou, Zhejiang, China