Sintilimab Combined With Anlotinib and Taxane-Based Chemotherap for Recurrent/Metastatic Nasopharyngeal Carcinoma

A Prospective, Single-Arm Phase II Clinical Trial on the Efficacy and Safety of Sintilimab Combined With Anlotinib and Taxane-Based Chemotherapy in Previously Immunotherapy-Treated Recurrent/Metastatic Nasopharyngeal Carcinoma

This is a prospective, single-arm Phase 2 study to evaluate the efficacy and safety of sintilimab combined with anlotinib and taxane-based chemotherapy in patients with recurrent (not unable to locally curative treatment) or metastatic NPC who failed at least first-line platinum-containing standard regimen and/or anti PD-1/L1.

Thirty-three recurrent (not unable to locally curative treatment) or metastatic NPC patients who had failed at least first-line platinum-containing standard regimen and/or anti PD-1/L1 were eligible to receive sintilimab combined with anlotinib and taxane-based chemotherapy (comprising docetaxel <75mg/m²>, paclitaxel <175mg/m²>, or nab-paclitaxel <260mg/m²>; Select one chemotherapeutic drug not previously used.), once every 3 weeks for up to 6 cycles, following sintilimab and anlotinib once every 3 weeks for 2 years. All patients will be treated until disease progression as determined by the investigator based on RECIST 1.1 criteria, intolerable toxicity, subject withdrawal of informed consent, initiation of new antitumor therapy, loss of follow-up, death, or study completion, whichever occurs first. Regular visits and imaging examinations will be conducted to evaluate the efficacy and safety of the treatment regimen.

Inclusion Criteria:

1. Sign a written informed consent before implementing any trial-related procedures.
2. Age is 18 or older and 65 or younger.
3. Nasopharyngeal nonkeratinizing carcinoma (differentiated or undifferentiated, i.e. WHO type II or III) with histological or cytological evidence.
4. Recurrent or metastatic nasopharyngeal carcinoma that has failed previous treatment with first-line platinum-containing standard regimens and/or second-line standard regimens.
5. At least one measurable lesion according to the evaluation criteria for the efficacy of solid tumors (RECIST v1.1) is considered measurable if a lesion in a previously irradiated field is confirmed to have progressed;
6. Participants with asymptomatic brain metastases or stable symptoms after local treatment may be enrolled, provided they meet the following criteria: 1) Measurable lesions outside the central nervous system; 2) No central nervous system symptoms or no symptom exacerbation within at least two weeks; 3) No need for glucocorticoid therapy, discontinued glucocorticoid treatment within seven days prior to initial administration, or stabilized glucocorticoid dosage within seven days prior to initial administration reduced to below 10 mg/day prednisone (or equivalent dose)
7. Allow the subject to receive palliative radiotherapy (including cranial radiotherapy for symptomatic brain metastases), provided that the radiotherapy is completed at least 1 week prior to enrollment and that the toxicity associated with radiotherapy is restored to less than or equal to grade 1 (CTCAE 5.0, except for hair loss)
8. ECOG score 0-1.
9. Life expectancy> 3 months.
10. If there is a risk of pregnancy, all subjects (male or female) should use contraception with an annual failure rate of less than 1% throughout the treatment period and for 120 days after the last study drug administration (or 180 days after the last study drug administration).

Exclusion Criteria:

1. Diagnosis of a malignancy other than nasopharyngeal carcinoma within 5 years prior to the first dose (excluding cured basal cell carcinoma of the skin, squamous epithelial carcinoma of the skin, and/or cured carcinoma in situ that has been resected);
2. Participants are currently enrolled in an interventional clinical study treatment or have received another investigational drug or used an investigational device within 4 weeks prior to the first dose
3. Within 2 weeks before the first administration, patients received systemic treatment with traditional Chinese medicine or immunomodulatory drugs (including thymosin, interferon, interleukin, except for local use to control pleural effusion) for anti-tumor indications
4. Active autoimmune diseases requiring systemic therapy (e.g., disease-modifying agents, glucocorticoids, or immunosuppressants) that occurred within 2 years prior to the first treatment. Replacement therapy (e.g., thyroid hormone, insulin, or physiologically administered glucocorticoids for adrenal or pituitary insufficiency) is not considered systemic therapy
5. Study participants were receiving systemic glucocorticoid therapy (not including nasal, inhaled or other topical glucocorticoids) or any other form of immunosuppressive therapy within 7 days prior to the first study administration;
6. The presence of clinically uncontrolled pleural/abdominal effusion (no drainage is required or the subject does not show significant increase in fluid over 3 days of discontinuation of drainage is eligible for enrollment)
7. Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
8. Patients who are known to be allergic to the active ingredient or excipient of the study drug, sintilimab and anlotinib hydrochloride;
9. Patients with multiple factors affecting oral medications (e.g., dysphagia, postgastrectomy, chronic diarrhea, intestinal obstruction, etc.);
10. Cough, severe liver and kidney dysfunction;
11. Not fully recovered from toxicity and/or complications caused by any intervention prior to starting treatment (i.e., ≤1 grade or baseline, excluding fatigue or hair loss)
12. History of human immunodeficiency virus (HIV) infection (i.e., HIV 1/2 antibody positive);
13. Untreated active hepatitis B (defined as HBsAg-positive with HBV DNA copy count exceeding the upper limit of normal values in the laboratory department of the research center); Note: Eligible participants also include those meeting the following criteria: 1) HBV viral loa
14. Active HCV-infected subjects (HCV antibody positive and HCV-RNA levels above the detection limit);
15. Vaccinated with a live vaccine within 30 days prior to the first dose (Day 1 of Week 1); Note: Influenza vaccine injections for seasonal influenza are permitted within 30 days prior to the first dose; however, intranasal administration of live attenuated influenza vaccine is not permitted.
16. Pregnant or lactating women;
17. Participants with any severe or uncontrolled systemic diseases, such as: 1) significant and symptomatically severe abnormalities in rhythm, conduction, or morphology observed on resting electrocardiogram (e.g., complete left bundle branch block, second-degree or higher cardiac block, ventricular arrhythmias, or atrial fibrillation); 2) unstable angina, congestive heart failure, or chronic heart failure classified as NYHA Class II or higher; 3) myocardial infarction within six months prior to enrollment; 4) suboptimal blood pressure control (systolic>140 mmHg, diastolic>90 mmHg); 5) history of non-infectious pneumonia requiring glucocorticoid therapy within one year prior to first administration, or current clinical active interstitial lung disease; 6) active pulmonary tuberculosis; 7) active or uncontrolled infections requiring systemic treatment; 8) active diverticulitis, peritoneal abscess, or gastrointestinal obstruction; 9) liver disorders including cirrhosis, decompensated cirrhosis, acute/chronic active hepatitis; 10) poorly controlled diabetes (fasting blood glucose>10mmol/L); 11) urine protein ≥++ detected in urinalysis with confirmed 24-hour protein>1.0 g; participants with psychiatric disorders and poor treatment compliance
18. History or evidence of disease, abnormal treatment or laboratory test values that may interfere with the results of the trial and prevent the subject from participating in the study, or other conditions that the investigator deems unsuitable for enrollment, or other potential risks that the investigator deems unsuitable for participation in this study.