PD-1 Inhibitor Plus G-CSF in Recurrent/Metastatic NPC With First-line Treatment Failure

Study Overview
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Brief Summary
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Recurrence and metastasis are the main causes of treatment failure of NPC. Preliminary clinical studies have found that the overall response rate of PD-1 inhibitors in treating ≥2 line R/M NPC is about 25%. Recent studies have shown that G-CSF can significantly increase the proportion of effector cells dominated by CD4+ T cells, improve the diversity of peripheral blood TCR, and regulate the immune status of patients. Therefore, we suspect that G-CSF may have a synergistic effect on PD-1 inhibitor, thus enhance the efficacy of PD-1 inhibitor monotherapy.

Official Title
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Camrelizumab Plus PEG-rhG-CSF in Recurrent/Metastatic NPC With First-line Treatment Failure

Conditions
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PD-1 Inhibitor, G-CSF

Intervention / Treatment
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* Drug: Camrelizumab
* Drug: G-CSF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female; 18-75 years of age. Received one or more lines of therapy, which must include prior treatment with a platinum agent (except for patients who are unfit or refuse platinum-containing regimens) and must not be amenable to potentially curative radiotherapy or surgery. [Received neoadjuvant/adjuvant/concurrent platinum-containing regimen for radical therapy (radiotherapy or surgery), with recurrence ≤6 months following completion of therapy can be recognized as one line] Subjects diagnosed with pathological confirmed non-keratinizing (WHO-II/III) metastatic NPC, or subjects with recurrent NPC that is unfit for local treatment Patients must have at least 1 lesion that is measurable using RECIST v1.1 criteria. ECOG performance status of 0 or 1. Have recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to any anti-tumor therapy 4 weeks earlier. Except for hair loss, hair color change, nail change, fatigue, etc., which do not pose safety risks to subjects. Life expectancy more than 12 weeks. Patients must have adequate organ function (without blood transfusion, without growth factor or blood components support within 14 days before enrollment) as determined by: Absolute neutrophil count (ANC) ≥1.5×109/L; Platelet count ≥ 75×109/L; Hemoglobin ≥ 9 g/dL; serum total bilirubin (TBIL) ≤1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×upper limit of normal (ULN), (for subjects with liver metastases, TBIL ≤3×ULN ; ALT and AST≤5×ULN); Creatinine ≤1.5×ULN or creatinine clearance rate≥50 ml/min (Cockcroft-Gault formula); serum albumin ≥28 g/L; INR, APTT≤1.5 x ULN. 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. Be willing and able to provide written informed consent/assent for the trial. Exclusion Criteria: Subjects who underwent anti-PD-1 /PD-L antibody or anti-CTLA-4 antibody (or any other antibody acting on T cell synergistic stimulation or checkpoint pathway). Known history of hypersensitivity to any components of the Camrelizumab and PEG-rhG -CSF formulation or other monoclonal antibodies. Prior chemotherapy, targeted small molecule therapy, or radical therapy within 2 weeks prior to Study Day 1 Diagnosed and/or treated additional malignancy within 5 years of enrollment, with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin, and/or curatively-resected in situ cervical and/or breast carcinoma. 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. Active central nervous system metastases and/or carcinomatous meningitis Severe, uncontrolled angiocardiopathy (heart failure > class II NYHA, unstable angina, myocardial infarction within past 1 year, supraventricular or ventricular arrhythmia which need medical intervention, or QT interval male ≥ 450 ms, female ≥ 470 ms.). History of non-infectious pneumonitis that required steroids or current pneumonitis Active infection requiring systemic therapy Be known to have active tuberculosis. Human immunodeficiency virus (HIV) positive Hepatitis B or C positive Live vaccine within 30 days of planned start of study drug Underlying medical condition that, in the Investigator's opinion, would increase the risks of study drug administration or obscure the interpretation of toxicity determination or adverse events.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: G-CSF+Camrelizumab<br> | Drug: Camrelizumab<br>* PD-1 inhibitor: Camrelizumab, 200 mg, intravenously (IV) , Day 1, Q3W, until progressive disease (PD) or unacceptable toxicity for a maximum of up to 35 cycles (up to approximately 2 years).<br>Drug: G-CSF<br>* G-CSF: mecapegfilgrastim, 6 mg, subcutaneous injection, Day 1, Q3W, until stop using Camrelizumab, progressive disease (PD) or unacceptable toxicity.<br>|
| Active Comparator: Camrelizumab<br> | Drug: Camrelizumab<br>* PD-1 inhibitor: Camrelizumab, 200 mg, intravenously (IV) , Day 1, Q3W, until progressive disease (PD) or unacceptable toxicity for a maximum of up to 35 cycles (up to approximately 2 years).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | Defined as the proportion of patients whose tumors shrink to complete response (CR) or partial response (PR) and remain for a certain period of time according to RECIST 1.1 | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients who achieved disease control | Defined as the proportion of subjects who achieve CR+PR+stable disease (SD) for at least 4 weeks according to RECIST 1.1. | 1 year | 
| The proportion of patients who achieved clinical benefit | Defined as maintaining the efficacy of CR+PR+SD for at least 6 months according to RECIST 1.1. | 1 year | 
| median progression-free survival | Defined as the period from the start of enrollment until disease progression or death from any cause. | 1 year | 
| Duration of response | Defined as the time from the first assessment of CR and PR to the first assessment of PD or death caused by any cause according to RECIST 1.1. | 1 year | 
| Adverse events | assessed by NCI-CTC5.0 standard | 1 year |