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

NCT02721589 | Completed Phase 1 DMC

• 1 other identifier: SHR-1210-101
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 1

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

Conditions

Advanced Solid Tumors

Keywords

PD-1/PD-L1 Advanced Solid Tumor Immunotherapy

Outcome Measures

Primary Outcomes (2)

• Number of Participants Experiencing Adverse Events (AEs)

  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).

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

• Number of Participants Experiencing Severe AEs (SAEs)

  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).

  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 (16)

• 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).

• 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).

• 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).

• 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).

Study Arms (4)

Injection SHR-1210 1mg/kg Cohort

EXPERIMENTAL

Biological: SHR-1210

Injection SHR-1210 3mg/kg Cohort

EXPERIMENTAL

Biological: SHR-1210

Injection SHR-1210 200mg Cohort

EXPERIMENTAL

Biological: SHR-1210

Injection SHR-1210 10mg/kg Cohort

EXPERIMENTAL

Biological: SHR-1210

Interventions

SHR-1210 BIOLOGICAL

A fully human monoclonal immunoglobulin (IgG4 subtype)

Injection SHR-1210 10mg/kg Cohort; Injection SHR-1210 1mg/kg Cohort; Injection SHR-1210 200mg Cohort; Injection SHR-1210 3mg/kg Cohort

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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: 0-1.
• Life expectancy ≥ 12 weeks.
• With measurable and evaluable lesions according to the RECIST v1.1.

You may not qualify if:

• 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-1210.
• 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).

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

Cancer Hospital Affiliated to Zhongshan University

Guangzhou, Guangdong, 510060, China

Location

Related Publications (2)

• Ma Y, Cao J, Zhang Y, Liu Q, Fang W, Yang Y, Zhao Y, Yang Q, Zhao H, Zhang L. Phase I study of camrelizumab in patients with advanced solid tumors. Signal Transduct Target Ther. 2023 Feb 1;8(1):47. doi: 10.1038/s41392-022-01213-6. No abstract available.

  PMID: 36725836 DERIVED

• Fang W, Yang Y, Ma Y, Hong S, Lin L, He X, Xiong J, Li P, Zhao H, Huang Y, Zhang Y, Chen L, Zhou N, Zhao Y, Hou X, Yang Q, Zhang L. Camrelizumab (SHR-1210) alone or in combination with gemcitabine plus cisplatin for nasopharyngeal carcinoma: results from two single-arm, phase 1 trials. Lancet Oncol. 2018 Oct;19(10):1338-1350. doi: 10.1016/S1470-2045(18)30495-9. Epub 2018 Sep 10.

  PMID: 30213452 DERIVED

MeSH Terms

Interventions

camrelizumab

Study Officials

• Yiding Xing

  Jiangsu Hengrui Pharmaceutical Co., Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2016
• First Posted: March 29, 2016
• Study Start: April 6, 2016
• Primary Completion: November 17, 2019
• Study Completion: November 17, 2019
• Last Updated: February 28, 2023

Record last verified: 2023-02

Locations

CN (1)