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A Study of Anlotinib and AK105 Injection in Subjects With Gastrointestinal Tumors, Urinary System Tumors, Neuroendocrine Tumors

Primary Purpose

Gastrointestinal Tumors, Urinary System Tumors, Neuroendocrine Tumors

Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
AK105
Anlotinib
Sponsored by
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastrointestinal Tumors, Urinary System Tumors, Neuroendocrine Tumors

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 1. Cohort 1:Histopathologically confirmed metastatic or inoperable cholangiocarcinoma failed with first-line or above chemotherapy.

Cohort 2: Histopathologically confirmed recurrent or metastatic colorectal cancer that is not suitable for surgery with MSI-H or dMMR.

Cohort 3: Histopathologically confirmed metastatic or recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Cohort 4:Histopathologically confirmed local progression or metastatic urothelial carcinoma that is not suitable for surgery.

Cohort 5:Low- and medium-grade (G1 or G2) late gastrointestinal pancreatic neuroendocrine tumor (NET) subjects diagnosed by pathology." 2.18 years and older; Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; Life expectancy ≥ 3 months.

3.At least one measurable lesion. 4.The main organs function are normally. 5. 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.

6. Understood and signed an informed consent form.

Exclusion Criteria:

  • 1.Has used anti-angiogenic drugs such as bevacizumab, erlotinib, apatinib, sorafenib, sunitinib, and endothelium or against PD-1, PD-L1 and other related immunotherapeutic drugs.

    2. HER2 positive in cohort 3. 3. Has received chemotherapy, radiotherapy or other treatments within 4 weeks prior to the first dose.

    4.Has brain metastases with symptoms or symptoms control for less than 2 months.

    5.Has diagnosed and/or treated additional malignancy within 5 years prior to the first dose.

    6.Has multiple factors affecting oral medication. 7.Has uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.

    8.Has unrelieved spinal cord compression. 9.Imaging shows that tumors invade large blood vessels. 10.Has hemoptysis within 1 month prior to the first dose and maximum daily hemoptysis ≥2.5 mL.

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

    12.Has received surgery, or unhealed wounds within 4 weeks before the first dose.

    13. Has artery/venous thrombosis prior to the first dose within 6 months. 14. Has drug abuse history that unable to abstain from or mental disorders 15. Has any serious and / or uncontrolled disease. 16. Has received vaccination or attenuated vaccine within 4 weeks prior to the first dose.

    17.Hypersensitivity to recombinant humanized anti-PD-1 monoclonal or its components.

    18. Immunosuppressive therapy with immunosuppressive agents or systemic or absorbable local hormones (dosage > 10 mg/day prednisone or other therapeutic hormones) is required for the purpose of immunosuppression, and is still in use for 2 weeks after the first dose.

    19.Diagnosed as immunodeficiency or receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy (dose >10 mg/day of prednisone or other therapeutic hormones) and continued to be used for 2 weeks prior to the first dose 20. Has participated in other anticancer drug clinical trials within 4 weeks. 21. According to the judgement of the researchers, there are other factors that subjects are not suitable for the study.

Sites / Locations

  • Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeRecruiting
  • Beijing Hospital
  • Peking Union Medical College Hospital
  • Jiangsu Cancer HospitalRecruiting
  • Harbin Medical University Cancer Hospital
  • Jinan Central HospitalRecruiting
  • Shanxi Provincial Cancer Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Anlotinib and AK105 injection

Arm Description

AK105 200mg intravenously (IV) on day 1 of each 21-day cycle plus Anlotinib capsules 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)

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
December 17, 2019
Last Updated
June 16, 2020
Sponsor
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT04207463
Brief Title
A Study of Anlotinib and AK105 Injection in Subjects With Gastrointestinal Tumors, Urinary System Tumors, Neuroendocrine Tumors
Official Title
A Phase II, Open, Single-arm, Multi-cohort, Multicenter Study of Anlotinib and AK105 Injection in Subjects With Gastrointestinal Tumors, Urinary System Tumors, Neuroendocrine Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Unknown status
Study Start Date
June 3, 2020 (Actual)
Primary Completion Date
December 31, 2020 (Anticipated)
Study Completion Date
May 30, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
AK105 is a humanized monoclonal antibody that specially binds to PD-1. Anlotinib is a small molecule tyrosine kinase inhibitor. Based on the mechanism study, tumor vascular abnormalities promote tissue hypoxia and increase lactic acid, thereby activating immunosuppression and inhibiting T cell function. Anti-angiogenic drugs enhance the infiltration of effector immune cells by inducing normalization of blood vessels and reducing immunosuppression.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastrointestinal Tumors, Urinary System Tumors, Neuroendocrine Tumors

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Anlotinib and AK105 injection
Arm Type
Experimental
Arm Description
AK105 200mg intravenously (IV) on day 1 of each 21-day cycle plus Anlotinib capsules 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)
Intervention Type
Drug
Intervention Name(s)
AK105
Intervention Description
AK105 is a humanized monoclonal antibody that specifically binds to PD-1. AK105 has a typical antibody structure and is composed of two lgG1 subtype heavy chains and two kappa subtypes light chains covalently linked by disulfide bonds.
Intervention Type
Drug
Intervention Name(s)
Anlotinib
Intervention Description
a multi-target receptor tyrosine kinase inhibitor
Primary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
Percentage of subjects achieving complete response (CR) and partial response (PR).
Time Frame
up to 96 weeks
Secondary Outcome Measure Information:
Title
Disease control rate(DCR)
Description
Percentage of subjects achieving complete response (CR) and partial response (PR) and stable disease (SD).
Time Frame
up to 96 weeks
Title
Duration of Response (DOR)
Description
DOR defined as time from earliest date of disease response to earliest date of disease progression based on radiographic assessment.
Time Frame
up to 96 weeks
Title
Progression-free survival (PFS)
Description
PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause.
Time Frame
up to 96 weeks
Title
Overall survival (OS)
Description
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.
Time Frame
up to 120 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 1. Cohort 1:Histopathologically confirmed metastatic or inoperable cholangiocarcinoma failed with first-line or above chemotherapy. Cohort 2: Histopathologically confirmed recurrent or metastatic colorectal cancer that is not suitable for surgery with MSI-H or dMMR. Cohort 3: Histopathologically confirmed metastatic or recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma. Cohort 4:Histopathologically confirmed local progression or metastatic urothelial carcinoma that is not suitable for surgery. Cohort 5:Low- and medium-grade (G1 or G2) late gastrointestinal pancreatic neuroendocrine tumor (NET) subjects diagnosed by pathology." 2.18 years and older; Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; Life expectancy ≥ 3 months. 3.At least one measurable lesion. 4.The main organs function are normally. 5. 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. 6. Understood and signed an informed consent form. Exclusion Criteria: 1.Has used anti-angiogenic drugs such as bevacizumab, erlotinib, apatinib, sorafenib, sunitinib, and endothelium or against PD-1, PD-L1 and other related immunotherapeutic drugs. 2. HER2 positive in cohort 3. 3. Has received chemotherapy, radiotherapy or other treatments within 4 weeks prior to the first dose. 4.Has brain metastases with symptoms or symptoms control for less than 2 months. 5.Has diagnosed and/or treated additional malignancy within 5 years prior to the first dose. 6.Has multiple factors affecting oral medication. 7.Has uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage. 8.Has unrelieved spinal cord compression. 9.Imaging shows that tumors invade large blood vessels. 10.Has hemoptysis within 1 month prior to the first dose and maximum daily hemoptysis ≥2.5 mL. 11.Has adverse events caused by previous therapy except alopecia that did not recover to ≤grade 1. 12.Has received surgery, or unhealed wounds within 4 weeks before the first dose. 13. Has artery/venous thrombosis prior to the first dose within 6 months. 14. Has drug abuse history that unable to abstain from or mental disorders 15. Has any serious and / or uncontrolled disease. 16. Has received vaccination or attenuated vaccine within 4 weeks prior to the first dose. 17.Hypersensitivity to recombinant humanized anti-PD-1 monoclonal or its components. 18. Immunosuppressive therapy with immunosuppressive agents or systemic or absorbable local hormones (dosage > 10 mg/day prednisone or other therapeutic hormones) is required for the purpose of immunosuppression, and is still in use for 2 weeks after the first dose. 19.Diagnosed as immunodeficiency or receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy (dose >10 mg/day of prednisone or other therapeutic hormones) and continued to be used for 2 weeks prior to the first dose 20. Has participated in other anticancer drug clinical trials within 4 weeks. 21. According to the judgement of the researchers, there are other factors that subjects are not suitable for the study.
Facility Information:
Facility Name
Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100021
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aiping Zhou, Doctor
Phone
021-38804518
Email
zhouap1825@126.com
First Name & Middle Initial & Last Name & Degree
Aiping Zhou, Doctor
Facility Name
Beijing Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100730
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yunbo Zhao, Doctor
Phone
010-85136715
First Name & Middle Initial & Last Name & Degree
Yunbo Zhao, Doctor
Facility Name
Peking Union Medical College Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100730
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jianfeng Zhou, Doctor
Phone
010-69158750
First Name & Middle Initial & Last Name & Degree
Jianfeng Zhou, Doctor
Facility Name
Jiangsu Cancer Hospital
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210009
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jifeng Feng, Doctor
Phone
025-83283415
First Name & Middle Initial & Last Name & Degree
Jifeng Feng, Doctor
Facility Name
Harbin Medical University Cancer Hospital
City
Harbin
State/Province
Jilin
ZIP/Postal Code
150081
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yanqiao Zhang, Doctor
Phone
0451-86298278
First Name & Middle Initial & Last Name & Degree
Yanqiao Zhang, Doctor
Facility Name
Jinan Central Hospital
City
Jinan
State/Province
Shandong
ZIP/Postal Code
250013
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yuping Sun, Doctor
Phone
0531-68623306
First Name & Middle Initial & Last Name & Degree
Yuping Sun, Doctor
Facility Name
Shanxi Provincial Cancer Hospital
City
Xi'an
State/Province
Shanxi
ZIP/Postal Code
710061
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zijun Liao, Doctor
Phone
029-85276142
First Name & Middle Initial & Last Name & Degree
Zijun Liao, Doctor

12. IPD Sharing Statement

Learn more about this trial

A Study of Anlotinib and AK105 Injection in Subjects With Gastrointestinal Tumors, Urinary System Tumors, Neuroendocrine Tumors

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