Clinical trial NCT03995472: A Study of SHR-1501 Combined With SHR-1316 in Patients With Advanced Tumors
Official title: A Phase I Clinical Study to Evaluate the Tolerability, Safety, Pharmacokinetics and Efficacy of SHR-1501 in Combination With SHR-1316 in Patients With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Malignancies
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-06-24
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and tolerability of SHR-1501 in combination with SHR-1316 in patients with advanced malignancies and to provide a recommended dose (RP2D) for subsequent clinical studies.


Eligibility criteria: Inclusion Criteria:

• All Patients All patients must meet all the following criteria to be eligible to participate:

1. Voluntarily participate in this clinical study, understand the research procedure and be able to sign informed consent in writing;
2. Subjects must be willing and able to follow the research protocol;
3. Aged 18-75 years old when the informed consent form is signed;
4. Have a histologically or cytologically confirmed diagnosis of advanced or metastatic tumor malignancy;
5. Patients' malignancies must be relapsed or refractory to standard treatment, or patients cannot tolerate standard treatment, or patients have actively refused standard therapy;
6. FFPE tumor tissue or unstained slides of tumor sample must be obtained from patients enrolled in the dose expansion or indication expansion stage, both preserved samples collected within 6 months before the first dose (or up to 12 months prior to the first dose) and fresh samples (preferred) are acceptable;
7. Eastern Cooperative Oncology Group ECOG PS score of 0-1;
8. Have a life expectancy of ≥ 12 weeks;
9. Adequate organ function defined according to the protocol, These results should be completed within 14 days prior to the first study treatment:
10. Non-surgically sterilized women of childbearing age or male subjects are required to consent to the use of at least one medically approved contraceptive (eg intrauterine devices, contraceptives or condoms) is performed during the study treatment period and within 3 months of the end of the study treatment period.

Exclusion Criteria:

1. Patients with cancerous meningitis (ie meningeal metastasis);
2. Patients with active central nervous system (CNS) metastasis.
3. Spinal cord compression that cannot be radically treated with surgery and/or radiotherapy cannot be enrolled.
4. Patients with double cancer or more serious cancer;
5. Patients with a history of autoimmune diseases;
6. Significant clinical significance in the history of cardiovascular disease;
7. Arterial/venous thrombosis events such as cerebrovascular accidents deep vein thrombosis and pulmonary embolism within 6 months prior to first administration;
8. Have a history of immunodeficiency including HIV infection;
9. Active hepatitis B or hepatitis C patients;
10. Any disease or symptom that is not appropriate for inclusion in this study determined by the investigator.;
11. Patients have undergone major surgery within 28 days prior to the first dose (except for diagnostics);
12. Those who used a live attenuated vaccine within 4 weeks prior to the first dose or expect a live attenuated vaccine during the study period;
13. Those who received other clinical trials within 4 weeks prior to the first study;
14. Those who received systemic immunosuppressive therapy within 2 weeks prior to the first study dose;
15. Patients who have previously received allogeneic bone marrow transplantation or solid organ transplantation;
16. A history of severe allergic reactions to other monoclonal antibody/fusion protein drugs;
17. Mental illness, alcohol abuse, drug abuse or substance abuse;
18. Any disease or condition that causes reasonable suspicion to prohibit the use of the study drug or affect the interpretation of the study results or the patient is at high risk of treatment complications (any other disease, metabolic disorder, physical examination results or laboratory tests abnormalities);
19. Pregnant or lactating women or women planning to become pregnant during the study.

Primary outcomes:
measure: Dose-limiting toxicity and Maximum tolerated dose
timeFrame: Approximately 42 Days.
measure: Recommended Phase 2 dose (RP2D)
timeFrame: Approximately 2 years
measure: Adverse event/Serious adverse event
timeFrame: Approximately 2 years
Secondary outcomes:
measure: Pharmacokinetic (PK)
timeFrame: Approximately 2 years
measure: Pharmacokinetic (PK)
timeFrame: Approximately 2 years
measure: Pharmacokinetic (PK)
timeFrame: Approximately 2 years
measure: Pharmacokinetic (PK)
timeFrame: Approximately 2 years
measure: Pharmacokinetic (PK)
timeFrame: Approximately 2 years
measure: Pharmacokinetic (PK)
timeFrame: Approximately 2 years
measure: Pharmacokinetic (PK)
timeFrame: Approximately 2 years
measure: Pharmacokinetic (PK)
timeFrame: Approximately 2 years
measure: Pharmacokinetic (PK)
timeFrame: Approximately 2 years
measure: Pharmacokinetic (PK)
timeFrame: Approximately 2 years
measure: Pharmacokinetic (PK)
timeFrame: Approximately 2 years
measure: Pharmacokinetic (PK)
timeFrame: Approximately 2 years
measure: Pharmacokinetic (PK)
timeFrame: Approximately 2 years
measure: Pharmacokinetic (PK)
timeFrame: Approximately 2 years
measure: Immune related features
timeFrame: Approximately 2 years
measure: Immune related features
timeFrame: Approximately 2 years
measure: Immune related features
timeFrame: Approximately 2 years
measure: Immune related features
timeFrame: Approximately 2 years
measure: Objective response rate
timeFrame: Approximately 2 years
measure: Disease control rate
timeFrame: Approximately 2 years
measure: Duration of response
timeFrame: Approximately 2 years
measure: progression-free survival
timeFrame: Approximately 2 years
measure: 12 months overall survival
timeFrame: Approximately 2 years
measure: Durable clinical benefit rate at 6 month
timeFrame: Approximately 2 years
measure: Immunogenicity
timeFrame: Approximately 2 years
Other outcomes:
Locations:
city: Liverpool
country: Australia
facility: Sydney Southwest Private Hospital
state: New South Wales
city: Randwick
country: Australia
facility: Scientia Clinical Research
state: New South Wales
city: South Brisbane
country: Australia
facility: Icon Cancer Centre South Brisbane
state: Queensland
city: Tugun
country: Australia
facility: John Flynn Private Hospital
state: Queensland
city: Guangzhou
country: China
facility: Guangdong General Hospital & Guangdong Academy of Medical Sciences
state: Guangdong
Study officials:
affiliation: Guangdong General Hospital & Guangdong Academy of Medical Sciences
name: Yilong Wu, MD
role: STUDY_DIRECTOR
References: