A Study of Anti-PD-1 Antibody With or Without BL-B01D1 as Maintenance Therapy Following Anti-PD-1 Antibody Plus Chemotherapy for the First-line Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma (PANKU-NPC02)

A Phase III Randomized Controlled Clinical Study of Anti-PD-1 Antibody With or Without BL-B01D1 as Maintenance Therapy Following Anti-PD-1 Antibody Plus Chemotherapy for the First-line Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma (PANKU-NPC02)

This trial is a registrational Phase III, randomized, open-label, multicenter study designed to evaluate the efficacy and safety of PD-1 monoclonal antibody combined with chemotherapy, followed by maintenance therapy with PD-1 monoclonal antibody with or without BL-B01D1, as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma.

Inclusion Criteria:

1. Voluntarily sign the informed consent form and comply with the protocol requirements;
2. Age ≥ 18 years;
3. Expected survival time ≥ 3 months;
4. Trial participants with nasopharyngeal carcinoma confirmed by histopathology and/or cytology, either initially diagnosed with metastatic disease or relapsed after curative-intent treatment;
5. Agree to provide tumor tissue samples obtained at or after the diagnosis of recurrent or metastatic disease;
6. Must have at least one measurable lesion as defined by RECIST v1.1;
7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
8. Toxicities from prior anti-tumor therapy must have recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0;
9. No severe cardiac dysfunction, with left ventricular ejection fraction ≥ 50%;
10. Organ function levels must meet the required criteria;
11. Urine protein ≤ 1+ or < 1000 mg/24h;
12. For premenopausal women of childbearing potential, a pregnancy test must be performed within 7 days before starting treatment; serum pregnancy test must rule out pregnancy; they must not be breastfeeding and must use highly effective contraceptive methods throughout the entire treatment period and for 7 months after the last dose. For male trial participants whose partners are women of childbearing potential, adequate barrier contraception must be used throughout the entire treatment period and for 7 months after the end of treatment.

Exclusion Criteria:

1. Trial participants who have received prior systemic therapy;
2. Those who have received prior therapy targeting the mechanism of tumor immuno-oncology;
3. Those who have previously received antibody-drug conjugates (ADCs) using topoisomerase I inhibitors as the toxin, or EGFR- and/or HER3-targeting antibodies/ADCs;
4. Trial participants who have received systemic immunostimulatory agents within 4 weeks prior to the first dose;
5. Those who have received radical radiotherapy, major surgery, or extensive-field radiotherapy within 4 weeks prior to study randomization;
6. History of severe cardiac or cerebrovascular disease;
7. Those receiving long-term systemic corticosteroid therapy (e.g., prednisone >10 mg/day) prior to the first dose;
8. Active autoimmune diseases and inflammatory diseases;
9. Unstable thrombotic events requiring therapeutic intervention within 6 months prior to screening;
10. Prolonged QTc interval, complete left bundle branch block, third-degree atrioventricular block, or frequent and uncontrolled arrhythmias;
11. Diagnosis of active malignancy within 3 years prior to study randomization;
12. Hypertension inadequately controlled by two antihypertensive agents;
13. Trial participants with poorly controlled blood glucose;
14. History of interstitial lung disease (ILD) requiring steroid therapy, current ILD, or radiation pneumonitis of Grade ≥2;
15. Concurrent pulmonary diseases resulting in clinically severe impairment of respiratory function;
16. Active central nervous system (CNS) metastases;
17. Severe infection occurring within 4 weeks prior to study randomization;
18. Trial participants with massive serosal cavity effusion, symptomatic serosal cavity effusion, or poorly controlled serosal cavity effusion;
19. Imaging findings indicating tumor invasion or encasement of abdominal, thoracic, or cervical structures;
20. Severe, non-healing wounds, ulcers, or bone fractures within 4 weeks prior to signing informed consent;
21. Trial participants with clinically significant bleeding or obvious bleeding tendency within 4 weeks prior to signing informed consent;
22. Trial participants with inflammatory bowel disease, history of extensive bowel resection, history of immune-mediated enteritis, intestinal obstruction, or chronic diarrhea;
23. Trial participants with a history of allergy to recombinant humanized antibodies or hypersensitivity to the investigational drug;
24. History of autologous or allogeneic stem cell transplantation;
25. Positive for human immunodeficiency virus (HIV) antibodies, active hepatitis B virus (HBV) infection, or hepatitis C virus (HCV) infection;
26. History of severe neurological or psychiatric disorders;
27. Receipt of other unapproved investigational drugs or treatments within 4 weeks prior to study randomization;
28. Trial participants who plan to receive, or have received, live vaccines within 28 days prior to study randomization;
29. Other conditions deemed by the investigator to make the participant unsuitable for participation in this clinical trial due to complications or other circumstances.