A Study of Anlotinib Combined With AK105 Injection in Subjects With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Advanced Solid Tumor
- Registration Number
- NCT04291248
- Lead Sponsor
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
- Brief Summary
This study is designed to evaluate the efficacy and safety of Anlotinib combined with AK105 injection or AK105 monotherapy in subjects with MSI-H or dMMR advanced solid tumors. In this study, 138 subjects will be enrolled, and those who met the admission criteria will divide into cohort 1 (anlotinib combined with AK105) and cohort 2 (AK105 ). The first phase of this study is a randomized, open-label, parallel-controlled, multicenter design, in which 30 subjects are randomly enrolled in two cohorts. The second phase is to continue enrollment of cohort 1 or cohort 2 when which cohort has the better clinical benefit than the other one.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 138
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Histopathologically confirmed MSI-H or dMMR advanced malignant solid tumors. 2. Has provided previously achieved tumor tissue samples or fresh samples. 3. 18 years and older; Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; Life expectancy ≥ 3 months.
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At least one measurable lesion. 5. The main organs function are normally. 6.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.
7.Understood and signed an informed consent form.
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1.Has used against PD-1, PD-L1 and other related immunotherapeutic drugs. 2. Has received chemotherapy, radiotherapy or other treatments within 4 weeks prior to the first dose.
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Has brain metastases with symptoms or symptoms control for less than 2 months.
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Has diagnosed and/or treated additional malignancy within 3 years prior to the first dose.
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Has multiple factors affecting oral medication. 6.Has uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
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Has unrelieved spinal cord compression. 8. Imaging shows that tumors invade large blood vessels. 9. Has hemoptysis within 1 month prior to the first dose and maximum daily hemoptysis ≥2.5 mL.
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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 dose.
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Has artery/venous thrombosis prior to the first dose within 6 months. 13. Has drug abuse history that unable to abstain from or mental disorders. 14. Has any serious and / or uncontrolled disease. 15. Has received vaccination or attenuated vaccine within 4 weeks prior to the first dose.
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Hypersensitivity to recombinant humanized anti-PD-1 monoclonal or its components.
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Has active autoimmune diseases requiring systemic treatment occurred within 2 years before the first administration.
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.
- Has a history of active TB. 20. Has participated in other anticancer drug clinical trials within 4 weeks. 20. According to the judgement of the researchers, there are other factors that subjects are not suitable for the study.
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Anlotinib+AK105 injection AK105 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). Anlotinib+AK105 injection Anlotinib 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). AK105 injection AK105 AK105 200mg intravenously (IV) on day 1 of each 21-day cycle.
- Primary Outcome Measures
Name Time Method Overall response rate (ORR) assessed by Independent Review Committee (IRC) up to 96 weeks Percentage of subjects achieving complete response (CR) and partial response (PR) based on IRC.
- Secondary Outcome Measures
Name Time Method Overall response rate (ORR) assessed by investigator up to 96 weeks Percentage of subjects achieving complete response (CR) and partial response (PR) based on investigator.
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 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.
Trial Locations
- Locations (9)
Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
🇨🇳Beijing, Beijing, China
The Second Affiliated Hospital of The PLA Air Force Medical University
🇨🇳Xi'an, Shanxi, China
Jiangsu Cancer Hospital
🇨🇳Nanjing, Jiangsu, China
Shanxi Cancer Hospital
🇨🇳Xi'an, Shanxi, China
Beijing Hospital
🇨🇳Beijing, Beijing, China
Peking University International Hospital
🇨🇳Beijing, Beijing, China
Tianjin Cancer Hospital
🇨🇳Tianjin, Tianjin, China
Chinese Academy of Medical Sciences, Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, China
The Third Affiliated Hospital of Harbin Medical University
🇨🇳Harbin, Heilongjiang, China