A Study of Anlotinib Hydrochloride Capsule Combined With AK105 Injection in Subject With Advanced Gastric and Gastro-oesophageal Junction Adenocarcinoma

Study Overview
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Brief Summary
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This is a randomized, controlled, open-label, multicenter study to evaluate efficacy of AK105 injection combined with Anlotinib Hydrochloride Capsules versus standard second-line chemotherapy. Patients are treated with AK105 injection combined with Anlotinib Hydrochloride Capsules or standard second-line chemotherapy, with 1:1 random ratio.

Official Title
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A Randomized, Open-label, Controlled, Multicenter Phase III Study of Hydrochloride Capsule Combined With AK105 Injection Versus Standard Second-line Chemotherapy for Advanced Gastric and Gastro-oesophageal Junction Adenocarcinoma

Conditions
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Advanced Gastric and Gastro-oesophageal Junction Adenocarcinoma

Intervention / Treatment
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* Drug: Anlotinib hydrochloride capsule
* Drug: AK105 injection
* Drug: Paclitaxel injection
* Drug: Docetaxel injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Understood and signed an informed consent form; 2.Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; Life expectancy ≥ 3 months; 3. Histopathology or cytology confirmed as metastatic or local advanced gastric and gastro-oesophageal junction adenocarcinoma; 4. First-line standard chemotherapy regimen in patients with advanced gastric or gastroesophageal junction adenocarcinoma after treatment failure; 5. Has at least one measurable lesion; 6. Weight ≥40 kg or BMI ≥18.5; 7. Adequate organ function; 8. 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. Exclusion Criteria: 1. Histopathology confirmed as squamous cell carcinoma, carcinoid, undifferentiated carcinoma, or other gastric cancer; 2. HER2 positive; 3. Has received paclitaxel or docetaxel in the first-line treatment; 4. Has received paclitaxel or docetaxel in the neoadjuvant or adjuvant treatment regimen and have relapsed or metastasized within 6 months after the last dose; 5. Has other malignant tumors within 5 years; 6. Has used anti-angiogenic drugs such as anlotinib, apatinib, lenvatinib, sorafenib, sunitinib, bevacizumab, or related immunotherapy drugs for PD-1, PD-L1, etc; 7. Severe hypersensitivity after administration of other monoclonal antibodies; 8. Has spinal cord compression, cancerous meningitis and symptomatic brain metastasis； 9. Has adverse events caused by previous therapy except alopecia that did not recover to ≤grade 1; 10. Has received radiotherapy, chemotherapy and surgery within 4 weeks before the first dose; 11. Has gastrointestinal bleeding tendency within 4 weeks before the first dose; 12. The tumor has invaded important blood vessels and will cause fatal bleeding; 13. Has multiple factors affecting oral medication; 14. Has uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage; 15. Has any active autoimmune disease or history of autoimmune disease; 16. Immunosuppressant or systemic or absorbable local hormone therapy is required to achieve the aim of immunosuppression (dose &gt; 10mg/ day prednisone or other therapeutic hormones) and is still used within 2 weeks after the first administration; 17. Has any serious and / or uncontrolled disease; 18. Has active viral infection; 19. Has participated in other anticancer drug clinical trials within 4 weeks; 20. According to the judgement of the investigators, there are other factors that may lead to the termination of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anlotinib hydrochloride capsule + AK105 injection<br>Anlotinib hydrochloride capsule 12mg 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) plus AK105 200mg intravenously (IV) on Day 1 of each 21-day cycle. | Drug: Anlotinib hydrochloride capsule<br>* Anlotinib hydrochloride capsule 12mg 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).<br>Drug: AK105 injection<br>* AK105 200mg intravenously (IV) on Day 1 of each 21-day cycle.<br>|
| Active Comparator: Standard Second-line Chemotherapy<br>Participants receive 80 mg/m² IV paclitaxel on Days 1, 8 and 15 of each 28-day cycle, or 75mg/m² docetaxel every 3 weeks of each 21-day cycle until disease progression or unacceptable toxicity. | Drug: Paclitaxel injection<br>* Paclitaxel injection 80mg / m² IV on Days 1, 8 and 15 of each 28-day cycle.<br>Drug: Docetaxel injection<br>* Docetaxel injection 75mg / m² IV every 3 weeks of each 21-day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | OS defined as the time from randomization 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. | up to 45 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause. | up to 45 weeks | 
| Overall response rate (ORR) | Percentage of subjects achieving complete response (CR) and partial response (PR). | up to 45 weeks | 
| Disease control rate (DCR) | Percentage of subjects achieving complete response (CR) and partial response (PR) and stable disease (SD). | up to 45 weeks | 
| Duration of response (DOR) | DOR defined as time from earliest date of disease response to earliest date of disease progression based on radiographic assessment. | up to 45 weeks |