A Study of TQB2450 Injection Combined With Anlotinib Hydrochloride Capsule as Second-line Treatment in Subjects With Advanced Biliary Cancer

Study Overview
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Brief Summary
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This study is a randomized, parallel controlled, multicentre phase III clinical trial to evaluate the efficacy and safety of TQB2450 combined with anlotinib versus chemotherapy as second-line treatment in subjects with advanced biliary cancer.

Official Title
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A Randomized, Open-label, Parallel Controlled, Multi-center Phase III Study of TQB2450 Injection Combined With Anlotinib Hydrochloride Capsule Versus Chemotherapy as Second-line Treatment in Subjects With Advanced Biliary Cancer

Conditions
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Advanced Biliary Cancer

Intervention / Treatment
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* Drug: TQB2450 Injection
* Drug: Anlotinib hydrochloride
* Drug: Oxaliplatin injection
* Drug: Capecitabine tablets
* Drug: Gemcitabine hydrochloride injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Histologically or cytologically confirmed biliary adenocarcinoma, including intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC) and gallbladder cancer (GBC). 2.18 years and older,Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; Life expectancy ≥ 3 months;Weight ≥40 kg or BMI ≥18.5. 3. At least one measurable lesion (based on RECIST 1.1). 4. Previous first-line gemcitabine or fluorouracil-based combination chemotherapy failed. 5.Adequate laboratory indicators. 6. No pregnant or breastfeeding women, and a negative pregnancy test. 7. Understood and Signed an informed consent form. Exclusion Criteria: 1. Tumor disease and medical history: Has central nervous system metastases (CNS) and/or cancerous meningitis or leptomeningeal carcinomatosis; Has other malignant tumors within 5 years; Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary with blood vessels is unclear; Severe bone damage caused by tumor bone metastasis; Has uncontrolled and repeated drainage pleural effusion, pericardial effusion, and ascites; Partial or complete intestinal obstruction and complete biliary obstruction that cannot be relieved; 2. Previous anti-tumor therapy: Has received Anlotinib Hydrochloride Capsules, Bevacizumab Injection, and immune checkpoint inhibitors such as PD-1, PD-L1, and CTLA-4 in prior treatment; Have received anti-tumor therapy within 4 weeks before the first administration; Unalleviated toxicity ≥ grade 1 due to any previous anticancer therapy; 3.Comorbidities and medical history: Active hepatitis B or C; Kidney abnormalities; Abnormal thyroid function; Cardiovascular abnormalities; Gastrointestinal abnormalities; History of immunodeficiency; Has risk of bleeding; Uncontrollable active bacterial, fungal or viral infections; Lung diseases, such as interstitial pneumonia, obstructive lung disease, and history of symptomatic bronchospasm; Allergies to the ingredients of the study drug; Have a history of neurological or psychiatric disorders According to the researcher's point of view, other severe, acute or chronic medical or mental illnesses or laboratory abnormalities that may increase the risks associated with participating in the study, or may interfere with the interpretation of the study results; Have a history of pituitary or adrenal dysfunction Has received major surgical treatment, open biopsy, or obvious traumatic injury within 28 days before the first administration; Long-term unhealed wound or fracture; Has drug abuse history that unable to abstain from or mental disorders; 4. Has participated in other clinical trials within 30 days before the study. 5. Has vaccinated with vaccines or attenuated vaccines within 4 weeks prior to first administration. 6. Pregnant or breastfeeding women. 7. 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

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: TQB2450+Anlotinib<br>TQB2450 1200 mg administered intravenously (IV) on Day 1 of each 21-day cycle ,Anlotinib capsules 12 mg given orally, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21). | Drug: TQB2450 Injection<br>* TQB2450 1200 mg administered intravenously (IV) on Day 1 of each 21-day cycle.<br>Drug: Anlotinib hydrochloride<br>* Anlotinib capsules 12 mg given orally, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21).<br>|
| Active Comparator: Chemotherapy<br>Capecitabine tablets combined with oxaliplatin injection or gemcitabine hydrochloride injection. Each cycle is 3 weeks. | Drug: Oxaliplatin injection<br>* Oxaliplatin injection 130 mg/m2 administered IV on Day 1 of each week in 3-week cycles;<br>Drug: Capecitabine tablets<br>* Capecitabine tablets total dose 2000 mg/m2, oral twice a day from Day 1-14 of each 3- week cycles;<br>Drug: Gemcitabine hydrochloride injection<br>* Gemcitabine hydrochloride injection administered 1000 mg/m2 IV on Day 1 and Day 8 of each week in 3-week cycles.<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. Participants 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 40 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 24 weeks | 
| Overall response rate (ORR) | Percentage of participants achieving complete response (CR) and partial response (PR). | up to 24 weeks | 
| Disease control rate（DCR） | Percentage of participants achieving complete response (CR) and partial response (PR) and stable disease (SD). | up to 24 weeks | 
| Duration of response（DOR） | The time when the participants first achieved complete or partial remission to disease progression. | up to 24 weeks | 
| Progression-free survival at 6 months | Percentage of participants whose PFS has achieved at least 6 months. | up to 6 months | 
| Overall survival at 6 months | Percentage of participants whose OS has achieved at least 6 months. | up to 6 months | 
| Overall survival at 12 months | Percentage of participants whose OS has achieved at least 12 months. | up to 12 months |