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

• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT04344158
• Collaborator: (none)
• Enrollment: 648
• Locations: 43
• Arms: 2
• Anticipated Duration (Months): 56
• Patients Per Site: 15.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Hepatocellular Carcinoma (HCC)	Drug: AK105 Injection; Drug: Anlotinib Hydrochloride Capsules; Drug: Sorafenib Tosylate Tablets	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 648 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Anticipated Study Start Date: May 1, 2020
• Anticipated Primary Completion Date: Jun 30, 2024
• Anticipated Study Completion Date: Dec 31, 2024

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. Overall response rate（ORR） [Up to 96 weeks]

   Percentage of subjects achieving complete response (CR) and partial response (PR).

3. Disease control rate（DCR） [Up to 96 weeks]

   Percentage of subjects achieving complete response (CR) and partial response (PR) and stable disease (SD).

4. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

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

1. 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.

2. 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.

3. 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.

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

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

6. 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.

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

2. 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.

3. 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.

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

5. 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.

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

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

8. 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.

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

10. Severe hypersensitivity after administration of other monoclonal antibodies.

11. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The First Affiliated Hospital of Bengbu Medical College	Bengbu	Anhui	China	233004
2	Anhui Provincial Hospital	Hefei	Anhui	China	230001
3	Anhui Provincial Cancer Hospital	Hefei	Anhui	China	230031
4	Beijing Ditan Hospital.Capital Medical University	Beijing	Beijing	China	100015
5	Beijing YouAn Hospital.Capital Medical University	Beijing	Beijing	China	100069
6	Beijing Cancer Hospital	Beijing	Beijing	China	100142
7	Peking Union Medical College Hospital	Beijing	Beijing	China	100730
8	Chinese Pla General Hospital	Beijing	Beijing	China	100853
9	Beijing Tsinghua Changgung Hospital	Beijing	Beijing	China	102218
10	Beijing Luhe Hospital.Capital Medical University	Beijing	Beijing	China
11	The Second Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing	China	400010
12	The First Affiliated Hospital of Fujian Medical University	Fuzhou	Fujian	China	350005
13	Fujian Provincial Cancer Hospital	Fuzhou	Fujian	China	350014
14	The first hospital of Lanzhou University	Lanzhou	Gansu	China	730000
15	Gansu Wuwei Tumour Hospital	Wuwei	Gansu	China	733000
16	Sun Yat-sen University Cancar Center	Guangzhou	Guangdong	China	510060
17	Guangdong Provincial People's Hospital	Guangzhou	Guangdong	China	510080
18	The First Affiliated Hospital，Sun Yat-sen University	Guangzhou	Guangdong	China	510080
19	Sun Yat-sen Memorial Hospital, Sun Yat-sen University	Guangzhou	Guangdong	China	510289
20	The First Affiliated Hospital，Sun Yat-sen University	Guangzhou	Guangdong	China
21	Guangxi Medical University Affiliated Tumor Hospital	Nanning	Guangxi Zhuang Autonomous Region	China	530021
22	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi Zhuang Autonomous Region	China	530021
23	Hainan General Hospital	Haikou	Hainan	China	570311
24	Cangzhou Central Hospital	Cangzhou	Hebei	China	061001
25	The Third Hospital of Hebei Medical University	Shijiazhuang	Hebei	China	050051
26	Affiliated Tumor Hospital of Harbin Medical University	Harbin	Heilongjiang	China	150081
27	Henan Province People's Hospital	Zhengzhou	Henan	China	450003
28	Henan Cancer Hospital	Zhengzhou	Henan	China	450008
29	Xiangya Hospital Central South University	Changsha	Hunan	China	410008
30	Hunan Cancar Hospital	Changsha	Hunan	China	410013
31	Fudan University Shanghai Cancer Center	Shanghai	Shanghai	China	200032
32	Zhongshan Hospital, Fuadn University	Shanghai	Shanghai	China	200032
33	The Second Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shanxi	China	710004
34	Tangdu Hospital of the Fourth Military Medical University of the People's Liberation Army of China	Xi'an	Shanxi	China	710038
35	First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shanxi	China	710061
36	Shanxi Provincial Cancer Hospital	Xi'an	Shanxi	China	710061
37	West China School of Medical Sichuan University	Chengdu	Sichuan	China	610041
38	Affiliated Hospital of Chengdu University	Chengdu	Sichuan	China	610081
39	Tianjin Medical University Cancar institute & Hospital	Tianjin	Tianjin	China	300060
40	Tianjin Third Central Hospital	Tianjin	Tianjin	China	300170
41	Tianjin First Central Hospital	Tianjin	Tianjin	China	300192
42	Tianjin Second People's Hospital	Tianjin	Tianjin	China	300192
43	The First Affiliated Hospital of Xinjiang Medical University	Ürümqi	Xinjiang Uygur Autonomous Region	China	830054

Sponsors and Collaborators

• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
• ClinicalTrials.gov Identifier: NCT04344158
• Other Study ID Numbers: ALTN-AK105-III-02
• First Posted: Apr 14, 2020
• Last Update Posted: Apr 15, 2020
• Last Verified: Apr 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Sorafenib

Study Results

No Results Posted as of Apr 15, 2020