Surufatinib Combined With Toripalimab in Recurrent or Metastatic Nasopharyngeal Carcinoma

Efficacy and Safety of Surufatinib Combined With Toripalimab in Recurrent or Metastatic Nasopharyngeal Carcinoma : a Prospective, Single Arm and Multicenter Trial

A prospective, single-arm,mutil-center study to assess the efficacy and safety of Surufatinib combined with Toripalimab in Recurrent or Metastatic Nasopharyngeal Carcinoma.

This study adopt Simon's two-stage Optimal designs method based on the primary endpoint of objective response rates. 4 patients were planned for the first stage. If one or more responses were observed, an additional 8 patients were to be accrued for a total of 12 patients. If 4 or more of the 12 patients achieved an objective response, then this study was designated worthy of additional investigation.Considering a 10% abscission rate, a total of 14 patients were included.

Surufatinib（250mg) will be orally administered within 1 hour after breakfast once a day (QD) , Toripalimab was administered intravenously at a fixed dose of 240 mg, and the infusion time was 60 ± 5 min, once every 21 days. The cumulative longest medication period is 2 years. Until disease progression, death, intolerable toxicity or other protocol specified end-of-treatment criteria is met .

Inclusion Criteria:

1. Provision of written Informed Consent Form (ICF) prior to any study specific procedures;

2. Male and Female aged between 18 and 75 years are eligible;

3. Histologically or cytologically confirmed that Recurrent or Metastatic Nasopharyngeal Carcinoma.

4. Patients must have received at least one standard platinum-based systemic chemotherapy regimen for the treatment of recurrent or metastatic NPC;Or the insensitivity or intolerance to platinum when the patient has previously received radical therapy;

5. Not suitable for local treatment (no radiotherapy or surgery);

6. Presence of at least one measurable target lesion for further evaluation according to RECIST criteria;

7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2;

8. Screening laboratory values must meet the following criteria (within past 14 days):

   • neutrophils ≥1.5×109/L ;
   • platelets ≥100×109/L；
   • hemoglobin ≥ 10 g/dL;
   • total bilirubin ≤ 1.5 x upper limit of normal (ULN); aspartic transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN without, and ≤ 5 x ULN with hepatic metastasis; serum creatinine ≤1.5╳ULN;

9. Ability to follow the program;

10. Toxic side effects of any previous chemotherapy have returned to less than or equal to NCI CTCAE1 level or baseline;

11. Predicted survival >3 months;

12. Males or female of childbearing potential must: agree to use using a reliable form of contraception (eg, oral contraceptives, intrauterine device, control sex desire, double barrier method of condom and spermicidal) during the treatment period and for at least 6 months after the last dose of study drug.

Exclusion Criteria:

1. The pathological type was neuroendocrine or small cell carcinoma;
2. Evidence with active CNS disease or previous brain metastases;
3. Prior received anti-tumor monoclonal antibodies or other investigational drugs within the first 4 weeks of enrollment;Previous treatment with other anti-PD-1 antibodies or other treatments targeting PD-1 / PD-L1.
4. Prior treatment with Surufatinib,or other antiangiogenic drugs were used ;
5. Patients were on immunosuppressive or systemic hormone therapy (doses greater than 10mg/day prednisone or other equivalent hormone) for immunosuppressive purposes and were still on it within 2 weeks prior to enrolment;
6. The patient has any active autoimmune disease or a history of autoimmune disease;
7. Have clinical cardiac symptoms or diseases that are not well controlled;
8. Patients with congenital or acquired immune deficiency;
9. Chemotherapy, targeted therapy and radiotherapy were received within 2 weeks before enrollment;
10. Patients who had a history of gastrointestinal perforation or had undergone major surgery 4 weeks before enrollment;
11. During the first 6 months of enrollment, there were arterial/venous thrombosis events, such as non-cardiovascular and cerebrovascular (including temporary ischemic attack), deep vein thrombosis (except for venous thrombosis caused by intravenous catheterization during pre-chemotherapy, which was determined by the investigators to be cured), and pulmonary embolism;
12. Patients with abnormal coagulation function (International normalized ratio (INR) >1.5 or partially activated prothrombin time (APTT) >1.5×ULN), bleeding tendency (such as active ulcer lesions in the stomach, occlusive blood in the stool (++), melenia and/or hematemesis and hemoptysis within 3 months) or lesions close to large vessels.The lesions involved in the skin or mucosal cavity are at risk of rupture;
13. Hypertension that cannot be controlled by medication;
14. Routine urine indicated more than 2+ urine protein or 24 hours urine protein >150mg/L;
15. Calibration of QT interval > 470MSEC;If the patient has an extended QT interval, but the investigator's study evaluates the prolonged period as due to a pacemaker (and no other cardiac abnormality), it is up to the investigator to determine whether the patient is eligible for the study;
16. Had other malignant tumors in the past 5 years (except for basal cell carcinoma or squamous cell carcinoma, cervical carcinoma in situ that have been effectively controlled);
17. Known to be allergic to drug ingredients;
18. Patients at risk of massive bleeding in the nasopharynx or deep ulcers in the nasopharynx.