NCT04207463

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
150

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jun 2020

Shorter than P25 for phase_2

Geographic Reach
1 country

7 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 17, 2019

Completed
3 days until next milestone

First Posted

Study publicly available on registry

December 20, 2019

Completed
6 months until next milestone

Study Start

First participant enrolled

June 3, 2020

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2020

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 30, 2021

Completed
Last Updated

June 17, 2020

Status Verified

June 1, 2020

Enrollment Period

7 months

First QC Date

December 17, 2019

Last Update Submit

June 16, 2020

Conditions

Gastrointestinal Tumors, Urinary System Tumors, Neuroendocrine Tumors

Outcome Measures

Primary Outcomes (1)

  • Overall response rate (ORR)

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

    up to 96 weeks

Secondary Outcomes (4)

  • Disease control rate（DCR）

    up to 96 weeks

  • Duration of Response (DOR)

    up to 96 weeks

  • Progression-free survival (PFS)

    up to 96 weeks

  • Overall survival (OS)

    up to 120 weeks

Study Arms (1)

Anlotinib and AK105 injection

EXPERIMENTAL

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)

Drug: AK105Drug: Anlotinib

Interventions

AK105DRUG

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.

Anlotinib and AK105 injection
AnlotinibDRUG

a multi-target receptor tyrosine kinase inhibitor

Anlotinib and AK105 injection

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • \. 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.
  • 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.
  • \. Understood and signed an informed consent form.

You may not qualify if:

  • 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.
  • \. HER2 positive in cohort 3. 3. Has received chemotherapy, radiotherapy or other treatments within 4 weeks prior to the first dose.
  • Has brain metastases with symptoms or symptoms control for less than 2 months.
  • Has diagnosed and/or treated additional malignancy within 5 years prior to the first dose.
  • Has multiple factors affecting oral medication. 7.Has uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
  • 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.
  • 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 dose.
  • \. 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.
  • Hypersensitivity to recombinant humanized anti-PD-1 monoclonal or its components.
  • \. 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.
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Beijing, Beijing Municipality, 100021, China

RECRUITING

Beijing Hospital

Beijing, Beijing Municipality, 100730, China

NOT YET RECRUITING

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

NOT YET RECRUITING

Jiangsu Cancer Hospital

Nanjing, Jiangsu, 210009, China

RECRUITING

Harbin Medical University Cancer Hospital

Harbin, Jilin, 150081, China

NOT YET RECRUITING

Jinan Central Hospital

Jinan, Shandong, 250013, China

RECRUITING

Shanxi Provincial Cancer Hospital

Xi’an, Shanxi, 710061, China

NOT YET RECRUITING

MeSH Terms

Conditions

Digestive System NeoplasmsNeuroendocrine Tumors

Interventions

anlotinib

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsDigestive System DiseasesNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasms, Nerve Tissue

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 17, 2019

First Posted

December 20, 2019

Study Start

June 3, 2020

Primary Completion

December 31, 2020

Study Completion

May 30, 2021

Last Updated

June 17, 2020

Record last verified: 2020-06

Locations

CN(7)