Clinical trial NCT04291248: A Study of Anlotinib Combined With AK105 Injection in Subjects With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Advanced Solid Tumor
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: MSI-H or dMMR Advanced Solid Tumors
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-03-02
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 1. 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.

  4. 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.

Exclusion Criteria:

* 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.

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

  4. Has diagnosed and/or treated additional malignancy within 3 years prior to the first dose.

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

  7. 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.

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

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

  12. 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.

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

  17. 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.

  19. 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.

Primary outcomes:
measure: Overall response rate (ORR) assessed by Independent Review Committee (IRC)
timeFrame: up to 96 weeks
Secondary outcomes:
measure: Overall response rate (ORR) assessed by investigator
timeFrame: up to 96 weeks
measure: Disease control rate（DCR）
timeFrame: up to 96 weeks
measure: Duration of Response (DOR)
timeFrame: up to 96 weeks
measure: Progression-free survival (PFS)
timeFrame: up to 96 weeks
measure: Overall survival (OS)
timeFrame: up to 96 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Beijing
country: China
facility: Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
state: Beijing
city: Beijing
country: China
facility: Chinese Academy of Medical Sciences, Peking Union Medical College Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University International Hospital
state: Beijing
city: Harbin
country: China
facility: The Third Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
state: Jiangsu
city: Xi'an
country: China
facility: The Second Affiliated Hospital of The PLA Air Force Medical University
state: Shanxi
city: Xi'an
country: China
facility: Shanxi Cancer Hospital
state: Shanxi
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
state: Tianjin
Study officials:
References: