A Study to Evaluate the Safety and Efficacy of SHR-1210, Gemcitabine and Cis-platinum by R/M NPC Subjects

An Open-Label, Single Center, Nonrandomized, Phase 1 Study to Evaluate Safety and Efficacy of Using the Combination Treatment of SHR-1210, Gemcitabine and Cis-platinum by Recurrent and Metastatic NPC

This is an open-label, single center, non-randomized, phase I trial to evaluate safety and efficacy of using the combination treatment of SHR-1210, gemcitabine and cis-platinum by recurrent and metastatic NPC.

Study Overview

• Status: Completed
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Drug: Gemcitabine; Biological: SHR-1210; Drug: cis-platinum

Detailed Description

This is an open-label, single center, nonrandomized, Phase 1 study to evaluate safety and efficacy of using the combination treatment of SHR-1210, gemcitabine and cis-platinum by recurrent and metastatic NPC.

The safety 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.Tumor response will be assessed by radiographic examination in screening visit and every 2 cycles after first dose.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Jiangsu Hengrui

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female 18-70 years of age.
2. Subjects diagnosed with pathological confirmed Primary metastatic nasopharyngeal carcinoma, or subjects with recurrent NPC that is unfit for local treatment.
3. Subjects with recurrent and metastatic NPC who did't receive any Systemic chemotherapy, neoadjuvant chemotherapy, concurrent radiochemotherapy and adjuvant chemotherapy 6 month before first dose are excepted.
4. ECOG performance status of 0 or 1.
5. Life expectancy more than 12 weeks.
6. Subjects enrolled must have measurable lesion(s) according to response evaluation criteria in solid (RECIST) v1.1.

7. Adequate laboratory parameters during the screening period as evidenced by the following:

   • Absolute neutrophil count ≥1.5*10E9/L;
   • Platelets ≥100*10E9/L;
   • Hemoglobin ≥9.0 g/dL;
   • Albumin (ALB) levels ≥2.8 g/dL;
   • Total bilirubin (TBIL)≥1.5 upper limit of normal (ULN)
   • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 2.5 upper limit of normal(ULN); for subjects with liver metastases, ALT and AST ≥5 ULN;
   • creatinine clearance rate ≥50mL/min;
8. 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
9. Able to understand and sign an informed consent form (ICF).

Exclusion Criteria:

1. 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;
2. Known history of hypersensitivity to any components of the SHR-1210 formulation;
3. 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;
4. Active central nervous system (CNS) metastases (indicated by clinical symptoms, cerebral edema, steroid requirement, or progressive disease);

5. Uncontrolled clinically significant medical condition, including but not limited to the following:

   • congestive heart failure (New York Health Authority Class > 2),
   • unstable angina,
   • myocardial infarction within the past 12 months, or
   • clinically significant supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention;
6. Active infection or an unexplained fever; 38.5℃ during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, subjects with tumor fever may be enrolled);
7. History of immunodeficiency including seropositivity for human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease;
8. 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;
9. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR-1210, gemcitabine and cis-platinum; Subjects receive SHR-1210 200mg (Day 1) and gemcitabine 1000mg/m2 (Day 1 and Day 8)and cis-platinum 80mg/m2 (Day 1) of each 21-day cycle for at most 6 cycles, followed by SHR-1210 200mg every three weeks (Q3W) maintenance for the remainder of the study or until documented PD.	Drug: Gemcitabine; gemcitabine; Other Names: Gemcitabine Hydrochloride for Injection; Biological: SHR-1210; SHR-1210 is a humanized anti-PD1 IgG4 monoclonal antibody.; Drug: cis-platinum; cis-platinum; Other Names: Cisplantin Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression of disease	progression of disease by radiographic examination	28 days

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Study Director: Qing Yang, MD, Jiangsu HengRui Medicine Co., Ltd.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2017
• Primary Completion (Actual): July 28, 2020
• Study Completion (Actual): July 31, 2020

Study Registration Dates

• First Submitted: April 13, 2017
• First Submitted That Met QC Criteria: April 17, 2017
• First Posted (Actual): April 20, 2017

Study Record Updates

• Last Update Posted (Actual): July 12, 2022
• Last Update Submitted That Met QC Criteria: July 11, 2022
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Cisplatin
• Other Study ID Numbers: SHR-1210-104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No