An Open-Label, Multiple Centers, Non-randomized, Dose-Escalation Phase 1 Study to Evaluate Safety and Tolerability of SHR-1210 in Subjects With Advanced Solid Tumors

Jiangsu HengRui Medicine Co., Ltd.1 site in 1 country126 target enrollmentApril 6, 2016

ConditionsAdvanced Solid Tumors

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Advanced Solid Tumors
Sponsor: Jiangsu HengRui Medicine Co., Ltd.
Enrollment: 126
Locations: 1
Primary Endpoint: Number of Participants Experiencing Severe AEs (SAEs)
Status: Completed
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This is an open-label, multiple centers, non-randomized, dose escalation phase I trial to evaluate safety and tolerability of SHR-1210 in patients with advanced solid tumors The primary objective is to assess safety and tolerability of SHR-1210 and identify recommended phase II doses of SHR-1210 in patients with advanced solid tumors

Registry

clinicaltrials.gov

Start Date

April 6, 2016

End Date

November 17, 2019

Last Updated

3 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Jiangsu HengRui Medicine Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male and female patients aged 18-70 years old.
•Patients with pathologically confirmed solid tumors (mainly lung, nasopharyngeal, esophageal/gastric and liver cancer).
•Patients with advanced (unresectable or metastatic) solid tumors who failed standard treatment (progressive disease or intolerance, such as to chemotherapy, targeted therapy, or immunotherapy other than those targeting PD-1/PD-L1) or with no effective treatment available.
•ECOG PS: 0-
•Life expectancy ≥ 12 weeks.
•With measurable and evaluable lesions according to the RECIST v1.1.

Exclusion Criteria

•Patients with any active autoimmune diseases or a history of autoimmune diseases (including but not limited to the following: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism; adult patients with vitiligo or completely relieved childhood asthma can be enrolled if they do not require any intervention; patients with asthma requiring medical interventions with bronchodilators cannot be enrolled).
•Patients who are currently using immunosuppressive agents, or systemic or absorbable local hormonal therapies for immunosuppression purposes (\> 10 mg/day prednisone or equivalent) and still use the above drugs within 2 weeks prior to enrollment.
•Patients who are known to be previously allergic to macromolecular protein preparations, or any component of SHR-
•Patients with clinically symptomatic metastases to central nervous system (e.g., cerebral edema requiring hormonal intervention, or progression of brain metastasis):
•Patients who have received treatment for brain or meningeal metastasis can be included if they are clinically stable (MRI) for at least 2 months and have discontinued systemic hormonal therapy (\> 10 mg/day prednisone or equivalent) for more than 2 weeks; 2)Non-small cell lung cancer patients with brain metastasis, except those requiring local radiotherapy, can be enrolled into 200 mg fixed dose group (refer to Study Design and Schedule of Activities sections).
•Patients with previous or concurrent malignancies at other sites (except for cured skin basal cell carcinoma and cervical carcinoma in situ).
•Patients with clinical symptoms or diseases of the heart that are not well controlled, such as (1) \> NYHA Class II cardiac failure, (2) unstable angina, (3) myocardial infarct within the past year, (4) clinically significant supraventricular or ventricular arrhythmia requiring treatment or interventions.
•Patients who have previously received radiotherapy, chemotherapy, hormone therapy, surgery, or molecular targeted therapy with an interval of less than 4 weeks from the completion of the treatment to this study medication (for subjects who have previously received chemotherapy with nitrosourea or mitomycin, the interval from the end of chemotherapy to the study enrollment is less than 6 weeks); patients whose AEs caused by previous treatment have not recovered to CTCAE Grade ≤ 1; patients who are still receiving anti-tumor treatment with traditional Chinese medicine 2 weeks before the study medication.
•Patients with active infection or unexplained fever \> 38.5 °C during screening or prior to the first dose (patients with tumor-induced fever may be enrolled as per the judgment of the investigator).
•Patients with congenital or acquired immunodeficiency (such as HIV infection), or active hepatitis (hepatitis B: HBsAg, Anti-HBs, HBeAg, Anti-HBc, Anti-HBe, HBV DNA ≥ 104/mL, hepatocyte transaminases, etc.; hepatitis C: HCV antibodies and HCV RNA).

Outcomes

Primary Outcomes

Number of Participants Experiencing Severe AEs (SAEs)

Time Frame: From the time the participants signed the informed consent to 90 days after the final dose (Up to 3 years and 7 months)

The safety assessment documented in this clinical study included any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of an investigational product, which were monitored per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version \[v\] 4.03 2010).

Number of Participants Experiencing Adverse Events (AEs)

Time Frame: From the time the participants signed the informed consent to 90 days after the final dose (Up to 3 years and 7 months)

Secondary Outcomes

Area Under the Serum Concentration-time Curve from dosing to the time of the last measured concentration (AUC 0-last) for SHR-1210(PK blood samples are collected multiple times on Cycle 1 (each cycle is 28 days) Day1, Day 8, Day 15, Day 22, Cycle 2 Day 1, Since Cycle 2, every 3 cycle Day 1, and the day disease progression (Up to 3 years and 7 months).)
C(ss, Max) of SHR-1210 after Multiple Dosing(PK blood samples are collected multiple times on Cycle 1 (each cycle is 28 days) Day1, Day 8, Day 15, Day 22, Cycle 2 Day 1, Since Cycle 2, every 3 cycle Day 1, and the day disease progression (Up to 3 years and 7 months).)
Objective Response Rate (ORR)(Up to 3 years and 7 months)
Disease Control Rate (DCR)(Up to 3 years and 7 months)
Volume of distribution (Vd) for SHR-1210(PK blood samples are collected multiple times on Cycle 1 (each cycle is 28 days) Day1, Day 8, Day 15, Day 22, Cycle 2 Day 1, Since Cycle 2, every 3 cycle Day 1, and the day disease progression (Up to 3 years and 7 months).)
Mean Residence Time (MRT) for SHR-1210(PK blood samples are collected multiple times on Cycle 1 (each cycle is 28 days) Day1, Day 8, Day 15, Day 22, Cycle 2 Day 1, Since Cycle 2, every 3 cycle Day 1, and the day disease progression (Up to 3 years and 7 months).)
Half-life (T½) for SHR-1210(PK blood samples are collected multiple times on Cycle 1 (each cycle is 28 days) Day1, Day 8, Day 15, Day 22, Cycle 2 Day 1, Since Cycle 2, every 3 cycle Day 1, and the day disease progression (Up to 3 years and 7 months).)
Maximum Observed Serum Concentration (Cmax) for SHR-1210(PK blood samples are collected multiple times on Cycle 1 (each cycle is 28 days) Day1, Day 8, Day 15, Day 22, Cycle 2 Day 1, Since Cycle 2, every 3 cycle Day 1, and the day disease progression (Up to 3 years and 7 months).)
Area Under the Serum Concentration-time Curve to infinite time (AUC 0-inf) for SHR-1210(PK blood samples are collected multiple times on Cycle 1 (each cycle is 28 days) Day1, Day 8, Day 15, Day 22, Cycle 2 Day 1, Since Cycle 2, every 3 cycle Day 1, and the day disease progression (Up to 3 years and 7 months).)
Time to Maximum Concentration (Tmax) for SHR-1210(PK blood samples are collected multiple times on Cycle 1 (each cycle is 28 days) Day1, Day 8, Day 15, Day 22, Cycle 2 Day 1, Since Cycle 2, every 3 cycle Day 1, and the day disease progression (Up to 3 years and 7 months).)
Number of Participants with Anti-drug Antibodies (ADAs) for SHR-1210(Blood samples for ADAs analysis are collected on Cycle 1 (each cycle is 28 days) Day1 to the end of treatment (Up to 3 years and 7 months).)
Clearance (Cl) for SHR-1210(PK blood samples are collected multiple times on Cycle 1 (each cycle is 28 days) Day1, Day 8, Day 15, Day 22, Cycle 2 Day 1, Since Cycle 2, every 3 cycle Day 1, and the day disease progression (Up to 3 years and 7 months).)
C(ss, Min) of SHR-1210 after Multiple Dosing(PK blood samples are collected multiple times on Cycle 1 (each cycle is 28 days) Day1, Day 8, Day 15, Day 22, Cycle 2 Day 1, Since Cycle 2, every 3 cycle Day 1, and the day disease progression (Up to 3 years and 7 months).)
Accumulation ratio based on Cmax (Rac, Cmax) for SHR-1210(PK blood samples are collected multiple times on Cycle 1 (each cycle is 28 days) Day1, Day 8, Day 15, Day 22, Cycle 2 Day 1, Since Cycle 2, every 3 cycle Day 1, and the day disease progression (Up to 3 years and 7 months).)
PD-1 receptor occupancy (RO) for SHR-1210(PD blood samples are collected multiple times on Cycle 1 (each cycle is 28 days) Day1, Day 8, Day 15, Day 22, Cycle 2 Day 1, Since Cycle 2, every 3 cycle Day 1, and the day disease progression (Up to 3 years and 7 months).)
Progression-free survival (PFS)(Up to 3 years and 7 months)