A Randomized, Open-label , Multi-cohort, Multicenter, Phase II Study of Anlotinib Combined With AK105 Injection in Subjects With MSI-H or dMMR Advanced Solid Tumor
Overview
- Phase
- Phase 2
- Intervention
- AK105
- Conditions
- MSI-H or dMMR Advanced Solid Tumors
- Sponsor
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
- Enrollment
- 138
- Locations
- 9
- Primary Endpoint
- Overall response rate (ORR) assessed by Independent Review Committee (IRC)
- Last Updated
- 6 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histopathologically confirmed MSI-H or dMMR advanced malignant solid tumors.
- •Has provided previously achieved tumor tissue samples or fresh samples.
- •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.
- •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.
Exclusion Criteria
- •1.Has used against PD-1, PD-L1 and other related immunotherapeutic drugs.
- •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 3 years prior to the first dose.
- •Has multiple factors affecting oral medication. 6.Has uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
- •Has unrelieved spinal cord compression.
- •Imaging shows that tumors invade large blood vessels.
- •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
- •Has received surgery, or unhealed wounds within 4 weeks before the first dose.
Arms & Interventions
Anlotinib+AK105 injection
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: AK105
Anlotinib+AK105 injection
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: Anlotinib
AK105 injection
AK105 200mg intravenously (IV) on day 1 of each 21-day cycle.
Intervention: AK105
Outcomes
Primary Outcomes
Overall response rate (ORR) assessed by Independent Review Committee (IRC)
Time Frame: up to 96 weeks
Percentage of subjects achieving complete response (CR) and partial response (PR) based on IRC.
Secondary Outcomes
- Overall response rate (ORR) assessed by investigator(up to 96 weeks)
- 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 96 weeks)