A Phase II Study to Evaluate HLX43 in Subjects With Recurrent/Metastatic Nasopharyngeal Carcinoma Failed or Intolerance to Second-line Therapy

A Phase II Study to Evaluate the Efficacy and Safety of HLX43 (Anti-PD-L1 ADC) in Subjects With Recurrent/Metastatic Nasopharyngeal Carcinoma (NPC) Failed or Intolerance to Second-line Therapy

The study is to explore the reasonable dosage and to evaluate the efficacy, safety and tolerability of HLX43 (Anti-PD-L1 ADC) in patients with recurrent/metastatic Nasopharyngeal Carcinoma (NPC) who failed or are intolerant to second-line herapy.

This study is an open-label phase II clinical study to explore the reasonable dosage and to evaluate the efficacy, safety and tolerability of HLX43 (Anti-PD-L1 ADC) in patients with recurrent/metastatic Nasopharyngeal Carcinoma (NPC) who failed or are intolerant to second-line therapy.

In this study, eligible subjects will be randomized at 1:1:1 ratio, and the patients will be administered with HLX43 at three different doses via intravenous infusion.

Inclusion Criteria:

1. Fully understand the study content, procedures, and potential adverse reactions before the trial, sign the informed consent form (ICF), voluntarily participate in the trial, and be able to complete the study per the protocol requirements;
2. Age ≥ 18 years at the time of signing the ICF, regardless of gender;
3. Histologically or cytologically confirmed recurrent/metastatic nasopharyngeal carcinoma;
4. Recurrent/metastatic nasopharyngeal carcinoma patients who have failed or are intolerant to at least two prior lines of chemotherapy (including at least one platinum-based regimen) and PD-1/PD-L1 inhibitor therapy. Intolerance is defined as experiencing CTCAE ≥ grade 3 adverse events;
5. At least one measurable lesion per RECIST v1.1 within 4 weeks before randomization;
6. Willing to provide archived (preferably within 2 years) or fresh tumor tissue specimens for the detection of PD-L1 expression.
7. At least 4 weeks (or 5 half-lives, whichever is shorter) since last major surgery, medical device treatment, radiotherapy (except palliative bone radiotherapy), cytotoxic chemotherapy, immunotherapy, or biological therapy; ≥2 weeks since last hormonal therapy or small molecule targeted therapy; ≥1 week since last traditional Chinese medicine treatment with anti-tumor indications or minor surgery; with treatment-related adverse events recovered to CTCAE v5.0 ≤ grade 1 (except grade 2 peripheral neuropathy and alopecia);
8. ECOG performance status 0-1 within 1 week before randomization;
9. Expected survival ≥ 3 months；
10. Adequate organ function within 1 week before randomization (no blood transfusion or colony-stimulating factors within 14 days prior to first dose)
11. Fertile participants must use ≥1 highly effective contraceptive method during the trial and for ≥6 months after last dose; females of childbearing potential must have negative pregnancy test within 7 days before enrollment.

Exclusion Criteria:

1. Recurrent nasopharyngeal carcinoma candidates eligible for curative local therapy (surgery or radiotherapy).
2. Imaging showing tumor invasion/encasement of major thoracic/cervical/pharyngeal blood vessels (may be exempted if investigators confirm no impact on trial participation).
3. History of other malignancies within 2 years prior to randomization (except radically treated early-stage malignancies).
4. Previous ≥Grade 3 immune-related adverse events during immunotherapy.
5. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
6. Symptomatic/untreated/progressing CNS or leptomeningeal metastases.
7. History of ≥Grade 3 radiation pneumonitis; steroid-requiring (non-infectious) interstitial lung disease (ILD), current ILD, or ILD unexcludable by imaging; or severe respiratory impairment from pulmonary disease.
8. Poorly controlled cardiovascular/cerebrovascular conditions including.
9. Candidates for organ/marrow transplantation or previous transplant recipients.
10. Active systemic infections requiring IV antibiotics within 2 weeks pre-randomization.
11. Use of strong CYP2D6/CYP3A inhibitors/inducers within 2 weeks pre-randomization.
12. Systemic corticosteroid use (>10mg prednisone/day equivalent) or immunosuppressants within 2 weeks pre-randomization. Exceptions: Topical/ocular/intra-articular/nasal/inhaled steroids; short-term prophylactic use for contrast agents.
13. Active/suspected autoimmune diseases. Exceptions: Hypothyroid patients on thyroid replacement; controlled type 1 diabetes with insulin.
14. Live/attenuated vaccines within 4 weeks pre-randomization (inactivated influenza vaccines permitted).
15. History of severe hypersensitivity to biologics/monoclonal antibodies or trial drug components.
16. Active tuberculosis.
17. Immunodeficiency disorders (HIV-positive or congenital/acquired immune deficiencies).
18. Active HBV/HCV infection or co-infection:
19. Pregnant/lactating women.
20. Investigators' judgment of clinical/lab abnormalities or other factors making participation inappropriate.