Clinical trial NCT04236362: A Study of TQB2450 Combined With Anlotinib in Subjects With Gynecological Cancer
Official title: A Phase Ib, Single Arm, Open-label Study of TQB2450 Combined With Anlotinib in Subjects With Relapsed / Refractory Gynecological Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Gynecological Cancer
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-01-22
Enrollment: 90
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: This is a single-arm, open-label, phase Ib clinical trial to evaluate the efficacy and safety of TQB2450 combined with anlotinib in subjects with gynecological cancer, including 34 ovarian cancer，34 endometrial cancer，22 cervical cancer.


Eligibility criteria: Inclusion Criteria:

1. Understood and signed an informed consent form;
2. 18 years and older, male or female, Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, life expectancy ≥ 3 months;
3. Histologically confirmed, unresectable recurrent/metastatic advanced gynecologic cancer, including ovarian, endometrial, and cervical cancer;
4. Subjects have received at least 1 line platinum-containing chemotherapy (minimum of 4 cycles of platinum-containing treatment) after tumor reduction, and meet any of the following：Platinum-resistant or refractory patients, including patients who have progressed or relapsed during previous platinum-containing chemotherapy regimens or within 6 months after the end of platinum-containing chemotherapy;
5. At least one measurable lesion according to the RECIST 1.1;
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.

Exclusion Criteria:

1. Has other non-epithelial ovarian tumors or borderline ovarian epithelial tumors;
2. Other malignant tumors that have appeared or are currently present within 5 years, except for cured cervical carcinoma in situ, non-melanoma skin cancer and superficial bladder tumors;
3. Has previously received immune drugs such as PD-1 / PD-L1, CTLA-4 or other tyrosine kinase inhibitors such as anlotinib hydrochloride;
4. Has received bevacizumab within 28 days before the first dose;
5. 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;
6. Expect to use any active vaccine against infectious diseases (such as influenza vaccine, chickenpox vaccine, etc.) within 28 days before the first dose or during the study period;
7. Patients diagnosed with immunodeficiency or undergoing systemic glucocorticoid therapy or any other form of immunosuppressive therapy (dose\> 10mg / day prednisone or other effective hormones) and continue to use it within 2 weeks before the first dose;
8. Active autoimmune diseases that require systemic treatment have occurred within 2 years before the first dose;
9. Subjects known to be allergic to the study drug or any of its excipients or have experienced a severe allergic reaction to other monoclonal antibodies;
10. Has uncontrollable symptoms of brain metastases, spinal cord compression, cancerous meningitis;
11. Has any bleeding or bleeding event ≥ CTC AE Grade 3 or unhealed wounds, ulcers or fractures within 4 weeks before the first dose;
12. Has clinically significant thyroid dysfunction before the first dose;
13. Has multiple factors affecting oral medication;
14. Has any severe acute complications before the first dose;
15. Has participated in other anti-tumor intervention clinical trials within 4 weeks before the first medication;
16. 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: Objective Response Rate (ORR)
timeFrame: up to 96 weeks
Secondary outcomes:
measure: Progression free survival (PFS)
timeFrame: up to 96 weeks
measure: Duration of Response (DOR)
timeFrame: up to 96 weeks
measure: Disease control rate（DCR）
timeFrame: up to 96 weeks
measure: Overall Survival (OS)
timeFrame: up to 120 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: The General Hospital of the People's Liberation Army
state: Beijing
city: Chongqing
country: China
facility: Cancer Hospital of Chongqing University
state: Chongqing
city: Lanzhou
country: China
facility: The First Hospital of Lanzhou University
state: Gansu
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Qinhuangdao
country: China
facility: First Hospital of Qinhuangdao
state: Hebei
Study officials:
References:
citation: Lan CY, Zhao J, Yang F, Xiong Y, Li R, Huang Y, Wang J, Liu C, Bi XH, Jin HH, Meng J, Zhao WH, Zhang L, Wang YF, Zheng M, Huang X. Anlotinib combined with TQB2450 in patients with platinum-resistant or -refractory ovarian cancer: A multi-center, single-arm, phase 1b trial. Cell Rep Med. 2022 Jul 19;3(7):100689. doi: 10.1016/j.xcrm.2022.100689.