A Study to Evaluate the Safety and Tolerability of Using the SHR-1210 by Advanced Solid Tumor Subjects

Hengrui Medicine

Status and phase: Completed; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Biological: SHR-1210

Study type: Interventional

Funder types: Industry

Identifiers

NCT02721589

SHR-1210-101

Details and patient eligibility

About

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

Enrollment: 126 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male and female patients aged 18-70 years old.
2. Patients with pathologically confirmed solid tumors (mainly lung, nasopharyngeal, esophageal/gastric and liver cancer).
3. 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.
4. ECOG PS: 0-1.
5. Life expectancy ≥ 12 weeks.
6. With measurable and evaluable lesions according to the RECIST v1.1.

Exclusion criteria

1. 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).
2. 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.
3. Patients who are known to be previously allergic to macromolecular protein preparations, or any component of SHR-1210.
4. Patients with clinically symptomatic metastases to central nervous system (e.g., cerebral edema requiring hormonal intervention, or progression of brain metastasis):

1)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).

5. Patients with previous or concurrent malignancies at other sites (except for cured skin basal cell carcinoma and cervical carcinoma in situ).

6. 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.

7. 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.

8. 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).

9. 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).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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126 participants in 4 patient groups

Injection SHR-1210 1mg/kg Cohort

Experimental group

Treatment:

Biological: SHR-1210

Injection SHR-1210 3mg/kg Cohort

Experimental group

Treatment:

Biological: SHR-1210

Injection SHR-1210 200mg Cohort

Experimental group

Treatment:

Biological: SHR-1210

Injection SHR-1210 10mg/kg Cohort

Experimental group

Treatment:

Biological: SHR-1210