Clinical trial NCT03996408: Study of TQB2450 Combined With Anlotinib in Subjects With Advanced Cholangiocarcinoma
Official title: Phase Ib Study to Evaluate the Pharmacokinetics, Safety and Efficacy of TQB2450 Injection(PD-L1 Antibody) Combined With Anlotinib in Subjects With Advanced Cholangiocarcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Advanced Cholangiocarcinoma
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-06-24
Enrollment: 42
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: TQB2450 is a humanized monoclonal antibody targeting programmed death ligand-1 (PD-L1), which prevents PD-L1 from binding to PD-1 and B7.1 receptors on T cell surface, restores T cell activity, thus enhancing immune response and has potential to treat various types of tumors.


Eligibility criteria: Inclusion Criteria:

1.18 and 75 years; Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; Life expectancy ≥ 3 months.

2. Histologically or cytologically confirmed inoperable or metastatic cholangiocarcinoma.

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

4. At least one measurable lesion. 5. Has failed with standard first-line chemotherapy or were not suitable for standard first-line chemotherapy.

6.The main organs function are normally. 7. 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.

8.Understood and signed an informed consent form.

Exclusion Criteria:

1. Prior therapy with VEGFR-target TKI included anlotinib or an anti-programmed cell death (PD)-1, anti-PD-L1, anti-PD-L2, anti-tumor necrosis factor CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody ,or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
2. Hypersensitivity to recombinant humanized anti-PD-1 monoclonal Abm or its components.
3. Has diagnosed and/or treated additional malignancy within 5 years prior to randomization. Exceptions include cured basal cell carcinoma of skin and carcinoma in situ of cervix.
4. Has any active autoimmune disease or a history of autoimmune disease.
5. Has immunosuppressive therapy with systemic or absorbable topical hormone therapy and replacement therapy for hypothyroidism with normal thyroid function within 2 weeks before the first dose.
6. Has multiple factors affecting oral medication.
7. Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
8. Has any signs of bleeding or a history of physical illness.
9. Has uncontrollable symptoms of brain metastasis, spinal cord compression, cancerous meningitis during screening within 8 weeks before first dose.
10. Has received chemotherapy, surgery, radiotherapy, the last treatment from the first dose less than 4 weeks, or oral targeted drugs for less than 5 half-lives, or oral fluorouracil pyridine drugs for less than 14 days, mitomycin C and nitrosourea for less than 6 weeks.
11. Has any serious and / or uncontrolled disease.
12. Has vaccinated with vaccines or attenuated vaccines, or received granulocyte colony stimulating factor(G -CSF)，or Granulocyte macrophage colony stimulating factor (GM-CSF) within 4 weeks prior to first dose.
13. According to the judgement of the researchers, there are other factors that may lead to the termination of the study. For example, other serious diseases including mental disorders need to be treated together, serious laboratory abnormalities, accompanied by family or social factors, which will affect the safety of the subjects, or the collection of data and samples.

Primary outcomes:
measure: Dose limiting toxicity (DLT)
timeFrame: up to 21 days
measure: Maximum tolerated dose (MTD)
timeFrame: up to 21 days
measure: Recommended Phase II dose (RP2D)
timeFrame: up to 24 months
measure: Overall response rate (ORR)
timeFrame: up to 24 months
Secondary outcomes:
measure: Disease control rate（DCR）
timeFrame: up to 24 months
measure: Progression-free survival (PFS)
timeFrame: up to 24 months
measure: Overall survival (OS)
timeFrame: up to 24 months
measure: Adverse Event
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
References: