Clinical trial NCT04203719: A Study of Anlotinib and AK105 Injection in Subjects With Advanced Head, Neck and Chest Cancer
Official title: A Phase II, Open, Single-arm, Multi-cohort, Multicenter Study of Anlotinib and AK105 Injection in Subjects With Advanced Head, Neck and Chest Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Advanced Head, Neck and Chest Cancer
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-12-18
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 1. Cohort 1：Histologically or cytologically confirmed head and neck squamous cell cancer, primary tumor sites including oropharynx, oral cavity, hypopharynx, or larynx.

Cohort 2：Histologically confirmed advanced/metastatic head and neck non-squamous cell cancer failed with standard treatment.

Cohort 3：Histologically confirmed undifferentiated thyroid cancer not suitable for surgery and failed with standard treatment.

Cohort 4：Histologically confirmed small cell lung cancer failed with only one platinum-containing chemotherapy.

Cohort 5：Histologically confirmed stage IIIB to IV non-squamous cell lung cancer failed with standard treatment.

Cohort 6：Histologically confirmed stage IIIB to IV squamous non-small cell lung cancer failed with at least one platinum-containing or other double-drug chemotherapy.

Cohort 7：Histologically confirmed recurrent/metastasis pleural mesothelioma and thymic cancer failed with at least one-line chemotherapy and not suitable for surgery or radiotherapy.

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. Providing tumor specimen obtained by biopsy or surgical sample within 2 years.

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

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

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

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

  6.Has unrelieved spinal cord compression. 7.Imaging shows that tumors invade large blood vessels. 8. Central lung squamous cell carcinoma with hollow. 9.Has adverse events caused by previous therapy except alopecia that did not recover to ≤grade 1.

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

  11. Has artery/venous thrombosis prior to the first dose within 6 months. 12. Has drug abuse history that unable to abstain from or mental disorders 13. Has any serious and / or uncontrolled disease. 14. Has received vaccination or attenuated vaccine within 4 weeks prior to the first dose.

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

  16.Has active autoimmune diseases requiring systemic therapy within 2 years prior to the first dose.

  17.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.

  18.Has participated in other anticancer drug clinical trials within 4 weeks. 19.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)
timeFrame: up to 96 weeks
Secondary outcomes:
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 120 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
state: Beijing
Study officials:
References: