Study of TQB2450 Combined With Anlotinib in Subjects With Advanced Cholangiocarcinoma

• ClinicalTrials.gov Identifier: NCT03996408
• Recruitment Status: Unknown
• First Posted: June 24, 2019
• Last Update Posted: October 30, 2019
• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
• Information provided by (Responsible Party): Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Advanced Cholangiocarcinoma	Drug: Anlotinib; Drug: TQB2450	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 42 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: June 24, 2019
• Estimated Primary Completion Date: December 31, 2020
• Estimated Study Completion Date: March 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Anlotinib + TQB2450; TQB2450 1200 mg IV on Day 1 of each 21-day cycle plus Anlotinib capsules 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).	Drug: Anlotinib; a multi-target receptor tyrosine kinase inhibitor; Drug: TQB2450; 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.

Outcome Measures

Primary Outcome Measures :

1. Dose limiting toxicity (DLT) [ Time Frame: up to 21 days ]
   DLT defined as any of the following events occurring during the study related to drugs : (1) ≥grade 3 non-hematologic toxicity; (2) Grade 4 neutropenia, thrombocytopenia, and hemoglobin reduction confirmed by at least 2 tests within 2 days; Grade 3 thrombocytopenia with bleeding tendency confirmed by at least 2 tests within 2 days; (3) Grade 3 neutropenia with fever confirmed at least 2 times within 2 days.
2. Maximum tolerated dose (MTD) [ Time Frame: up to 21 days ]
   MTD defined as the highest dose level at which less than or equal to 2 of 6 subjects experience dose limiting toxicity (DLT)
3. Recommended Phase II dose (RP2D) [ Time Frame: up to 24 months ]
   The RP2D defined as the lower dose level to MTD based on the safety profile
4. Overall response rate (ORR) [ Time Frame: up to 24 months ]
   Percentage of subjects achieving complete response (CR) and partial response (PR)

Secondary Outcome Measures :

1. Disease control rate（DCR） [ Time Frame: up to 24 months ]
   Percentage of subjects achieving complete response (CR) and partial response (PR) and stable disease (SD)
2. Progression-free survival (PFS) [ Time Frame: up to 24 months ]
   PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause
3. Overall survival (OS) [ Time Frame: up to 24 months ]
   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
4. Adverse Event [ Time Frame: up to 24 months ]
   Number of participants with adverse events

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Lin Shen, Master; 010-88196340; doctorshenlin@sina.cn

Locations

China, Beijing

Beijing Cancer Hospital; Recruiting

Beijing, Beijing, China, 100083

Contact: Lin Shen, Master 010-88196340 doctorshenlin@sina.cn

Sponsors and Collaborators

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

More Information

• Responsible Party: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
• ClinicalTrials.gov Identifier: NCT03996408
• Other Study ID Numbers: TQB2450-Ib-08
• First Posted: June 24, 2019
• Last Update Posted: October 30, 2019
• Last Verified: June 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Cholangiocarcinoma; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms