Tislelizumab Plus GX Versus Tislelizumab Plus GP in the Treatment of R/M NPC

Official title

A Phase III Clinical Study of Tislelizumab Combined With GX Regimen Versus Tislelizumab Combined With GP Regimen in the First-line Treatment of Recurrence or Metastasis (R/M) Nasopharyngeal Carcinoma (NPC)

Overview

The study is being conducted to evaluate the safety and efficacy of tislelizumab combined with GX regimen versus tislelizumab combined with GP regimen in the first-line treatment of nasopharyngeal carcinoma.

Interventions

• Drug Tislelizumab combined with GX
  Tislelizumab：200mg vgtt，q3w；treatment until disease progression, patients withdrawal of informed, or intolerable toxicity. Gemcitabine：1000mg/m2, vgtt, d1,8, q3w, repeat 4-6 cycles. Capecitabine: 1000mg/m2, bid，po, d1-14, q3; treatment until disease progression, patients withdrawal of informed, or intolerable toxicity.
• Drug Tislelizumab combined with GP
  Tislelizumab: 200mg vgtt，q3w；treatment until disease progression, patients withdrawal of informed, or intolerable toxicity. Gemcitabine: 1000mg/m2, vgtt, d1,8, q3w, repeat 4-6 cycles； Cisplatin: 80mg/m2, ivgtt, d1 (high-dose cisplatin antiemetic and hydration regimen), q3w，repeat 4 \~ 6 cycles.

Primary outcome measures

• To compare the progression-free survival of tislelizumab combined with GX regimen and tislelizumab combined with GP regimen based on the ITT analysis set evaluated by the researchers according to RECIST v1.1. [Time frame: up to approximately 3 years]

Secondary outcome measures (1)

• To compare the objective response rate of tislelizumab combined with GX regimen and tislelizumab combined with GP regimen based on the ITT analysis set evaluated by the researchers according to RECISTv1.1. [Time frame: up to approximately 3 years]

Eligibility criteria

Inclusion criteria

• Histological or cytological examination confirmed recurrence or metastasis of nasopharyngeal carcinoma;
• Patients who have not previously received systemic treatment for recurrent or metastatic diseases (For patients who have previously received induction chemotherapy, adjuvant chemotherapy or concurrent chemoradiotherapy, patients who relapsed at least 6 months after the cessation of chemotherapy can be enrolled).
• Age: 18-75 years old, male or female;
• Perfomance Status: 0\~1;
• At least one measurable lesion (according to RECIST v1.1, long diameter of measurable lesion scanned by spiral CT should be ≥ 10 mm or short diameter of swollen lymph node should be ≥ 15 mm; according to RECIST vl.1 standards, a previously treated lesion with local treatment can be used as target lesions after clear progress);
• Blood routine examination: 1) Hemoglobin (HB)≥ 90g / L; 2) Neutrophil count (ANC) ≥ 1.5 × 109 / L; 3) platelets (PLT) ≥ 80 × 109 / L;
• Liver function: 1) Serum total bilirubin (BIL) ≤ 1.5 times the upper limit of normal (ULN); 2) alanine aminotransferase (ALT), aspartate aminotransferase (AST\])< 2.5 × ULN; if liver metastasis, ALT and AST ≤ 5 × ULN; Renal function: Albumin ≥ 28g / L ；Serum creatinine (Cr) ≤ 1.5 × ULN，or creatinine clearance rate ≥ 60 ml / min ;
• Coagulation function : APTT and international normalized ratio (INR)< 1.5 × UNL;
• Patients of childbearing age agree to take appropriate contraceptive measures. Serum pregnancy test was negative in women of childbearing age within 2 weeks before enrollment.
• Patients agree to provide pathological tissue specimens (wax blocks or paraffin tissue sections 5-10 pieces) ;
• Expected survival ≥ 3 months;
• Patients volunteered to participate in this study and signed informed consent;

Exclusion criteria

• Patients with local recurrence and suitable for surgery or radiotherapy;
• Patients with a known history of severe allergies to monoclonal antibody therapy;
• Patients who had previously received PD-1 monoclonal antibody or PD-L1 monoclonal antibody or CTLA4 monoclonal antibody;
• Clinical significance of heart disease, including severe cardiac insufficiency : New York Heart Association (NYHA) cardiac insufficiency grade IV, unstable angina, acute myocardial infarction within 6 months before screening, congestive heart failure, Q-Tc interval greater than 500ms;
• Patients with autoimmune diseases requiring treatment, or patients with a history of systemic use of steroids / immunosuppressive agents, such as : hypophysitis, pneumonia, colitis, hepatitis, nephritis, hyperthyroidism, hypothyroidism;
• Other serious and uncontrollable concomitant diseases that may affect the compliance of the program or interfere with the interpretation of the results, including uncontrolled diabetes, or lung diseases (interstitial pneumonia, obstructive pulmonary disease, and symptomatic bronchial spasm) ;
• Known hepatitis B (HBV) (HBsAg positive and HBV-DNA ≥ 103IU / ml), hepatitis C ( HCV) infection (HCV antibody positive and HCV-RNA measurable) ; and other subjects with acquired and congenital immunodeficiency diseases, including, but not limited to, those infected with HIV;
• Severe active infection;
• Symptomatic patients with central nervous system metastasis;
• Patients with a history of other malignant tumors (unless those who have been cured for more than 5 years);
• Have a serious history of neurological or psychiatric disorders, including dementia or epilepsy;
• Drug abuse, medical, psychological or social conditions that may interfere with the participant 's participation in the study or the evaluation of the study results;
• Researchers believe that patients who are not suitable for enrollment.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Fudan University Shanghai Cancer Center — Shanghai

Identifiers

NCT: NCT06177301 · FUSCC-NC-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗