A Study to Evaluate the Safety and Tolerability of Using the SHR-1210 by Advanced Solid Tumor Subjects
Study Details
Study Description
Brief Summary
This is an open-label, single center, 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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
This is an open-label, single center, nonrandomized, dose-escalation Phase 1 study to evaluate safety and tolerability of SHR-1210 in subjects with advanced solid tumors who have failed current standard antitumor therapies.
The safety and tolerability of SHR-1210 will be assessed by ongoing reviews of clinical laboratory tests, Eastern Cooperative Oncology Group (ECOG) performance status, physical examination, electrocardiogram (ECG), and adverse events. Evaluations of immune safety will also be conducted (immune-related adverse events (AEs), or labs of autoimmune sera, inflammatory events, and immunogenicity). Safety evaluations (both clinical and laboratory) are performed at baseline, before each study treatment, and throughout the study.
Efficacy will be assessed every 8 weeks. The study consists of 3 periods: screening (up to 28 days before the first dose), treatment, and follow-up (up to 3 months after the last dose of study treatment).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Injection SHR-1210 200mg/vial |
Drug: SHR-1210
PD-1 antibody
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Dose limited toxicity [28 day]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male or female 18-70 years of age.
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Subjects diagnosed with histologically or cytologically confirmed solid tumors documented as advanced or metastatic disease. Subjects must be considered relapsed or refractory to standard therapies, have been intolerant to standard therapies, or have refused standard therapy.
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ECOG performance status of 0 or 1.
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Life expectancy ≥ 12 weeks.
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Subjects enrolled must have measurable lesion(s) according to response evaluation criteria in solid (RECIST) v1.1.
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Adequate laboratory parameters during the screening period as evidenced by the following:
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Absolute neutrophil count ≥ 1.5 × 109/L (1500/mm3)
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Platelets ≥ 100 × 109/L (100,000/mm3)
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Hemoglobin ≥ 9.0 g/dL (90 g/L)
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Albumin (ALB) levels ≥ 2.8 g/dL
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Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN)
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Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal(ULN); for subjects with liver metastases, ALT and AST ≤ 5 × ULN
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Serum creatinine ≤ 1.5 × ULN
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Female subjects agree not to be pregnant or lactating from beginning of the study screening through at least 3 months after receiving the last dose of study treatment. Both men and women of reproductive potential must be willing and able to employ a highly effective method of birth control/contraception to prevent pregnancy. A highly effective method of contraception is defined as one that results in a low failure rate, that is, less than 1% per year when used consistently and correctly
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Able to understand and sign an informed consent form (ICF).
Exclusion Criteria:
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Subjects with any active autoimmune disease or history of autoimmune disease, or history of syndrome that requires systemic steroids or immunosuppressive medications, including but not limited to the following: rheumatoid arthritis, pneumonitis, colitis (inflammatory bowel disease), hepatitis, hypophysitis, nephritis, hyperthyroidism, and hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy. Subjects with the following conditions will not be excluded from this study: asthma that requires intermittent use of bronchodilators, hypothyroidism stable on hormone replacement, vitiligo, Graves' disease, or Hashimoto's disease. Additional exceptions may be made with medical monitor approval.
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Known history of hypersensitivity to any components of the SHR-1210 formulation.
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Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses > 10 mg/day prednisone or equivalent are prohibited within 2 weeks before study drug administration. Note: corticosteroids used for the purpose of IV contrast allergy prophylaxis are allowed.
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Active central nervous system (CNS) metastases (indicated by clinical symptoms, cerebral edema, steroid requirement, or progressive disease). Subjects with brain or meningeal metastases that were previously treated must be clinically stable (magnetic resonance imaging [MRI] at least 4 weeks apart do not show evidence of new or enlarging metastases) and have discontinued immunosuppressive doses of systemic steroids (> 10 mg/day prednisone or equivalent) for at least 2 weeks before study drug administration.
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Uncontrolled clinically significant medical condition, including but not limited to the following: (1) congestive heart failure (New York Health Authority Class > 2), (2) unstable angina, (3) myocardial infarction within the past 12 months, or (4) clinically significant supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention.
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Prior systemic chemotherapy (< 6 weeks if chemotherapy including nitrosoureas or mitomycin), radiotherapy, immunotherapy, hormone therapy, surgery or target therapy within 4 weeks before the study drug administration, or any unresolved AEs > Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 (with the exception of any stable chronic toxicities not expected to resolve).
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Active infection or an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, subjects with tumor fever may be enrolled).
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History of immunodeficiency including seropositivity for human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease.
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Any other medical (eg, pulmonary, metabolic, congenital, endocrinal, or CNS disease), psychiatric, or social condition deemed by the investigator to be likely to interfere with a subject's rights, safety, welfare, or ability to sign informed consent, cooperate, and participate in the study or would interfere with the interpretation of the results.
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Investigational therapy administered within 4 weeks before the first dose of INCSHR01210.
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Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or risk of reactivation based on institutional guidelines and tests. Testing may include the following: HBV DNA, HCV RNA, hepatitis B surface antigen, or anti-hepatitis B core antibody.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cancer hospital affiliated to Zhongshan University | Guangzhou | Guangdong | China | 510060 |
Sponsors and Collaborators
- Jiangsu HengRui Medicine Co., Ltd.
Investigators
- Study Director: Yiding Xing, Doctor, Jiangsu Hengrui Pharmaceutical Co., Ltd.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SHR-1210-101