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

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

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.

Study Overview

• Status: Recruiting
• Conditions: PD-1 Inhibitor; G-CSF
• Intervention / Treatment: Drug: Camrelizumab; Drug: G-CSF

• Study Type: Interventional
• Enrollment (Anticipated): 68
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xi Ding, MD; Phone Number: 86-19880836260; Email: dingxi@sysucc.org.cn
• Study Contact Backup: Name: Ming-Yuan Chen, MD, PhD; Phone Number: 02087343392; Email: chmingy@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center
      • Contact: Ming-Yuan Chen, MD,PhD; Phone Number: 86-20-8734-2422; Email: chenmy@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female; 18-75 years of age.
2. 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]
3. Subjects diagnosed with pathological confirmed non-keratinizing (WHO-II/III) metastatic NPC, or subjects with recurrent NPC that is unfit for local treatment
4. Patients must have at least 1 lesion that is measurable using RECIST v1.1 criteria.
5. ECOG performance status of 0 or 1.
6. 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.
7. Life expectancy more than 12 weeks.

8. 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.

9. 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.
10. Be willing and able to provide written informed consent/assent for the trial.

Exclusion Criteria:

1. 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).
2. Known history of hypersensitivity to any components of the Camrelizumab and PEG-rhG -CSF formulation or other monoclonal antibodies.
3. Prior chemotherapy, targeted small molecule therapy, or radical therapy within 2 weeks prior to Study Day 1
4. 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.
5. 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.
6. Active central nervous system metastases and/or carcinomatous meningitis
7. 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.).
8. History of non-infectious pneumonitis that required steroids or current pneumonitis
9. Active infection requiring systemic therapy
10. Be known to have active tuberculosis.
11. Human immunodeficiency virus (HIV) positive
12. Hepatitis B or C positive
13. Live vaccine within 30 days of planned start of study drug
14. 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: G-CSF+Camrelizumab	Drug: Camrelizumab; 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).; Drug: G-CSF; G-CSF: mecapegfilgrastim, 6 mg, subcutaneous injection, Day 1, Q3W, until stop using Camrelizumab, progressive disease (PD) or unacceptable toxicity.
Active Comparator: Camrelizumab	Drug: Camrelizumab; 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).

What is the study measuring?

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
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
median progression-free survival	Defined as the period from the start of enrollment until disease progression or death from any cause.	1 year
Adverse events	assessed by NCI-CTC5.0 standard	1 year

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Anticipated): January 24, 2022
• Primary Completion (Anticipated): December 24, 2022
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: January 24, 2022
• First Submitted That Met QC Criteria: February 2, 2022
• First Posted (Actual): February 3, 2022

Study Record Updates

• Last Update Posted (Actual): February 3, 2022
• Last Update Submitted That Met QC Criteria: February 2, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: SYSUCC-CMY-2021-1215

Drug and device information, study documents

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