Clinical trial NCT03558191: SHR-1210 in Recurrent/Metastatic Nasopharyngeal Carcinoma Who Have Received Previous At Least Two Lines of Chemotherapy.
Official title: A Single-arm, Open Label, Multi-center, Phase 2 Study of SHR-1210 in Recurrent/Metastatic Nasopharyngeal Carcinoma Patients Who Have Received Previous At Least Two Lines of Chemotherapy.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nasopharyngeal Carcinoma
Keywords: Recurrent/Metastatic Nasopharyngeal Carcinoma
PD-1
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-06-15
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open label, single-arm, multi-center, phase 2 Study of SHR-1210 in recurrent/metastatic nasopharyngeal carcinoma(R/M NPC) patients who have received previous at least two lines of chemotherapy.

Detailed description: The primary objective of this phase 2 study is to assess objective response rate of SHR-1210 in patients with R/M NPC. The secondary objective is to observe the duration of response, progression free survival, time to response, overall survival and safety of SHR-1210 in R/M NPC. ADA is also investigated.

Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed Recurrent/Metastatic Nasopharyngeal Carcinoma (WHO type II-III);
2. Stage IVb R/M NPC failed from first-line platinum based chemotherapy and second-line chemotherapy;
3. ECOG performance status of 0 or 1;
4. Life expectancy ≥ 12 weeks;
5. Subjects must have measurable disease by CT or MRI per RECIST 1.1 criteria;
6. Can provide either a newly obtained or archival tumor tissue sample;
7. Adequate laboratory parameters during the screening period as evidenced by the following:

   1. Absolute neutrophil count ≥ 1.5 × 10\^9/L ;
   2. Platelets ≥ 90 × 10\^9/L;
   3. Hemoglobin ≥ 9.0 g/dL;
   4. Serum albumin ≥ 2.8g/dL;
   5. Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN), ALT and AST ≤ 1.5×ULN
   6. Creatinine clearance≥50 mL/min;
8. Female of child bearing potential, a negative urine or serum pregnancy test result within 72 h before study treatment. Participants of reproductive potential must be willing to use adequate contraception for the course of the study through 60 days after the last dose of SHR-1210. Male subjects with WOCBP partner must be willing to use adequate contraception for the course of the study through 120 days after the last dose of SHR-1210;
9. Subjects must be willing to participate in the research and sign an informed consent form (ICF);

Exclusion Criteria:

1. Subjects with any active autoimmune disease or history of autoimmune disease;
2. Subjects having clinical symptoms of metastases to central nervous system (such as cerebral edema, requiring steroids intervention, or brain metastasis progression);
3. Has a known additional malignancy within the last 5 years before study treatment with the exception of curatively treated basal cell and squamous cell carcinoma of the skin and/or curatively resected in-situ cervical and/or breast cancers;
4. Uncontrolled clinically significant heart disease, including but not limited to the following: (1) \> NYHA II congestive heart failure; (2) unstable angina, (3) myocardial infarction within the past 1 year; (4) clinically significant supraventricular arrhythmia or ventricular arrhythmia requirement for treatment or intervention;
5. Concurrent medical condition requiring the use of cortisol (\>10mg/day Prednisone or equivalent dose) or other systematic immunosuppressive medications within 14 days before the study treatment. Except: inhalation or topical corticosteroids. Doses \> 10 mg/day prednisone or equivalent for replacement therapy;
6. Has received prior anti-cancer monoclonal antibody (mAb), chemotherapy, targeted small molecule therapy within 4 weeks prior to first dosing or not recovered to ≤CTCAE 1 from adverse events (except for hair loss or neurotoxic sequelae from prior platinum therapy) due to a previously administered agent. Palliative irradiation should be ended 2 weeks before first dosing;
7. Active infection or an unexplained fever \> 38.5°C before two weeks of first dosing (subjects with tumor fever may be enrolled at the discretion of the investigator);
8. Known Human Immunodeficiency Virus (HIV) infection、active Hepatitis B or Hepatitis C;
9. Currently participating or has participated in a study within 4 weeks of the first dose of study medication;
10. Received a live vaccine within 4 weeks of the first dose of study medication. Pregnancy or breast feeding;
11. Received a systematic antibiotics within 4 weeks of the first dose of study medication.

    Pregnancy or breast feeding.
12. Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) or CTLA-4 agent;
13. Subjects are known to have a history of psychiatric substance abuse, alcoholism, or drug addiction;
14. Pregnancy or breast feeding;
15. According to the investigator, other conditions that may lead to stop the research.

Primary outcomes:
measure: Objective Response Rate (ORR) Assess by Independent Review Committee (IRC)
timeFrame: Tumor assessments were conducted at every 8 weeks from the first dose until the end of treatment, withdrawal of consent, or death ，whichever was earlier, approximately 3 years.
Secondary outcomes:
measure: ORR Assess by Investigators
timeFrame: Tumor assessments were conducted at every 8 weeks from the first dose until the end of treatment, withdrawal of consent, or death (whichever was earlier), approximately 3 years.
measure: Duration of Response (DoR)
timeFrame: Tumor assessments were conducted at every 8 weeks from the first dose until the end of treatment, withdrawal of consent, or death (whichever was earlier), approximately 3 years.
measure: Disease Control Rate (DCR)
timeFrame: Tumor assessments were conducted at every 8 weeks from the first dose until the end of treatment, withdrawal of consent, or death (whichever was earlier), approximately 3 years.
measure: Progression-Free Survival (PFS)
timeFrame: Tumor assessments were conducted at every 8 weeks from the first dose until the end of treatment, withdrawal of consent, or death (whichever was earlier), approximately 3 years.
measure: Overall Survival (OS)
timeFrame: Tumor assessments were conducted at every 8 weeks from the first dose until the end of treatment, withdrawal of consent, or death (whichever was earlier), approximately 3 years.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Cancer Center of Sun-Yat Sen University (CCSYSU)
state: Guangdong
Study officials:
affiliation: Cancer Center of Sun-Yat Sen University (CCSYSU)
name: Li Zhang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Jiangsu HengRui Medicine Co., Ltd.
name: Qing Yang, MD
role: STUDY_DIRECTOR
References: