Anrotinib and Tirelizumab in First-line Treatment of RM-NPC

Anrotinib Combined With Tirelizumab in First-line Treatment of Recurrent/Metastatic Nasopharyngeal Carcinoma

This is a prospective phase II clinical trial to evaluate the efficacy and safety of Anrotinib and Tirelizumab as a first-line treatment in patients with advanced recurrent or metastatic nasopharyngeal carcinoma.

Inclusion Criteria:

1. Had histopathologically confirmed nonkeratinizing recurrent/metastatic NPC (AJCC, 8th; the metastatic tissue biopsy is preferred, not necessary; locoregional recurrent lesion unfit for local treatment).
2. Subjects enrolled must have measurable lesion(s) according to response evaluation criteria in solid (RECIST) v1.1.
3. ECOG performance status of 0～2
4. Life expectancy more than 12 weeks.
5. unable or unwilling to undergo chemothraphy
6. Able to understand and sign an informed consent form (ICF).

Exclusion Criteria:

1. Uncontrolled clinically significant medical condition, including but not limited to the following: Hypertension that cannot be reduced to the normal range after antihypertensive drug congestive heart failure (New York Health Authority Class > 2), unstable angina, myocardial infarction within the past 12 months, clinically significant supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention;
2. Known history of hypersensitivity to any components of the Tirelizumab formulation or other monoclonal antibodies ;
3. Diagnosed with other malignant tumors.
4. Subjects with any active autoimmune disease or history of autoimmune disease, or history of syndrome that requires systemic steroids or immunosuppressive medications, including but not limited to the following: rheumatoid arthritis, pneumonitis, colitis (inflammatory bowel disease), hepatitis, hypophysitis, nephritis, hyperthyroidism, and hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy. Subjects with the following conditions will not be excluded from this study: asthma that requires intermittent use of bronchodilators, hypothyroidism stable on hormone replacement, vitiligo, Graves' disease, or Hashimoto's disease. Additional exceptions may be made with medical monitor approval;
5. Subjects with medical condition affecting oral drug absorption, such as dysphagia, chronic diarrhea and intestinal obstruction.
6. Active bleeding, ulcer, intestinal perforation, major surgery in the previous month; Patients with tumors close to the internal carotid artery or other large vessels, thus at risk of massive bleeding.
7. The laboratory test values within 7 days before enrollment do not meet the relevant standards.
8. 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 4 weeks before study drug administration. Note: corticosteroids used for the purpose of IV contrast allergy prophylaxis are allowed;
9. History of immunodeficiency including seropositivity for human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease; active tuberculosis (TB), anti-TB treatment is ongoing or within 1 year prior to screening; Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or risk of reactivation based on institutional guidelines and tests. Testing may include the following: HBV DNA, HCV RNA, hepatitis B surface antigen, or anti-Hepatitis B core antibody.
10. Subjects with comorbidities with long-term immunosuppressive drug therapy, or with systemic or local use of immunosuppressive doses of corticosteroids.
11. 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) and anti-angiogenic drugs.
12. Received any anti-infective vaccine (e.g. influenza vaccine, varicella vaccine, etc.) within 4 weeks prior to enrollment.
13. Any other medical (eg, pulmonary, metabolic, congenital, endocrinal, or CNS disease), psychiatric, or social condition deemed by the investigator to be likely to interfere with a subject's rights, safety, welfare, or ability to sign informed consent, cooperate, and participate in the study or would interfere with the interpretation of the results;