SHR-1210 in Recurrent/Metastatic Nasopharyngeal Carcinoma Who Have Received Previous At Least Two Lines of Chemotherapy.

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.

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03558191

Enrollment

156

Registered

2018-06-15

Start date

2018-08-14

Completion date

2021-12-30

Last updated

2024-03-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Nasopharyngeal Carcinoma

Keywords

Recurrent/Metastatic Nasopharyngeal Carcinoma, PD-1

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.

Interventions

DRUGSHR-1210

A humanized monoclonal immunoglobulin PD-1 antibody

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Objective Response Rate (ORR) Assess by Independent Review Committee (IRC)	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.	Percentage of participants achieved partial response (PR) or complete response (CR) based on IRC assessment according to the RECIST (version 1.1) is presented for this endpoint. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks (28 days) after the criteria for response are first met. Only tumor assessments performed on or before the start date of any further anti-cancer therapies are considered in the assessment of best overall response .

Secondary

Measure	Time frame	Description
ORR Assess by Investigators	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.	Percentage of participants achieved partial response (PR) or complete response (CR) based on investigator assessment according to the RECIST (version 1.1) is presented for this endpoint. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks (28 days) after the criteria for response are first met. Only tumor assessments performed on or before the start date of any further anti-cancer therapies are considered in the assessment of best overall response.
Duration of Response (DoR)	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.	DoR is defined, for participants with a CR or PR per RECIST version 1.1, as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or death, whichever occurs first.
Disease Control Rate (DCR)	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.	Percentage of participants achieving PR, CR or SD (SD ≥ 8 weeks) based on IRC assessment according to the RECIST version 1.1 is presented in this endpoint. DCR is a best overall response from the time of first dose to the documented objective progression or the subsequent anti-tumor therapy (whichever occurs first).
Progression-Free Survival (PFS)	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.	PFS is defined as the time from the first dose to the date of the first documentation of PD or death, whichever occurs first. PFS was based on investigator assessment according to the RECIST version 1.1. PFS time was summarized using the Kaplan-Meier method.
Overall Survival (OS)	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.	Overall Survival is defined as the time from the first dose to death due to any cause. OS time was measured using the Kaplan-Meier method.

Countries

China

Participant flow

Participants by arm

Arm	Count
SHR-1210 Injection SHR-1210 injection, 200 mg/dose, intravenous infusion over 30 minutes, once every 2 weeks . SHR-1210: A humanized monoclonal immunoglobulin PD-1 antibody	156
Total	156

Baseline characteristics

Characteristic	SHR-1210 Injection
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	7 Participants
Age, Categorical Between 18 and 65 years	149 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	156 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	0 Participants
Region of Enrollment China	156 participants
Sex: Female, Male Female	32 Participants
Sex: Female, Male Male	124 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	11 / 156
other Total, other adverse events	154 / 156
serious Total, serious adverse events	37 / 156

Outcome results

Primary

Objective Response Rate (ORR) Assess by Independent Review Committee (IRC)

Percentage of participants achieved partial response (PR) or complete response (CR) based on IRC assessment according to the RECIST (version 1.1) is presented for this endpoint. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks (28 days) after the criteria for response are first met. Only tumor assessments performed on or before the start date of any further anti-cancer therapies are considered in the assessment of best overall response .

Time frame: 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.

Population: The primary efficacy endpoint was analyzed in FAS.

Arm	Measure	Value (NUMBER)
SHR-1210 Injection	Objective Response Rate (ORR) Assess by Independent Review Committee (IRC)	28.3 percentage of participants

Secondary

Disease Control Rate (DCR)

Percentage of participants achieving PR, CR or SD (SD ≥ 8 weeks) based on IRC assessment according to the RECIST version 1.1 is presented in this endpoint. DCR is a best overall response from the time of first dose to the documented objective progression or the subsequent anti-tumor therapy (whichever occurs first).

Time frame: 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.