HLX43 for recurrent or metastatic nasopharyngeal carcinoma after multiple prior treatments

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

This trial will test whether the anti‑PD‑L1 antibody–drug conjugate HLX43 can help adults with recurrent or metastatic nasopharyngeal carcinoma who have not responded to or cannot tolerate at least two prior systemic therapies including prior PD‑1/PD‑L1 treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Shanghai Henlius Biotech (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, prednisone
• Locations: 15 sites (Fuzhou, Fujian and 14 other locations)
• Trial ID: NCT06839066 on ClinicalTrials.gov

What this trial studies

This is an open‑label phase II randomized study that gives HLX43 by intravenous infusion at one of three dose levels to patients with recurrent or metastatic nasopharyngeal carcinoma who have failed or are intolerant to multiple prior therapies. Eligible participants are randomized 1:1:1 to the three dose arms and followed for tumor response, safety, and tolerability. Key entry requirements include measurable disease per RECIST v1.1 and available tumor tissue for PD‑L1 testing. The trial will collect efficacy and adverse event data to help define a recommended dose and characterize activity in a heavily pretreated population.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed recurrent or metastatic nasopharyngeal carcinoma who have failed or are intolerant to at least two prior systemic therapies (including a platinum regimen) and prior PD‑1/PD‑L1 therapy, with at least one measurable lesion and available tumor tissue, are the intended participants.

Not a fit: Patients without prior platinum and PD‑1/PD‑L1 exposure, those lacking measurable disease, or those with poor organ function or other contraindications to an antibody‑drug conjugate are less likely to benefit from participation.

Why it matters

Potential benefit: If effective, HLX43 could offer a new treatment option that shrinks tumors or controls disease for patients with heavily pretreated nasopharyngeal carcinoma.

How similar studies have performed: PD‑1/PD‑L1 inhibitors have shown activity in nasopharyngeal carcinoma, but anti‑PD‑L1 antibody‑drug conjugates like HLX43 are a relatively novel approach with limited prior clinical data in this disease.

Eligibility criteria

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.

Where this trial is running

Fuzhou, Fujian and 14 other locations

• Fujian Cancer Hospital — Fuzhou, Fujian, China (Recruiting)
• Dongguan People's Hospital — Dongguan, Guangdong, China (Recruiting)
• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (Recruiting)
• The First Affiliated Hospital of Guangdong Pharmaceutical University — Guangzhou, Guangdong, China (Recruiting)
• Zhongshan City People's Hospital — Guangzhou, Guangdong, China (Recruiting)
• Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen — Shenzhen, Guangdong, China (Recruiting)
• Guangxi Medical University Cancer Hospital — Nanning, Guangxi, China (Recruiting)
• Guizhou Medical University Cancer Hospital — Guiyang, Guizhou, China (Recruiting)
• Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science & Technology — Wuhan, Hubei, China (Recruiting)
• Union Hospital Tongji Medical College Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)
• Xiangya Hospital of Central South University — Changsha, Hunan, China (Recruiting)
• First Affiliated Hospital of Gannan Medical University — Ganzhou, Jiangxi, China (Recruiting)
• Sichuan Cancer Hospital — Chengdu, Sichuan, China (Recruiting)
• West China Hospital of Sichuan University — Chengdu, Sichuan, China (Recruiting)
• Zhejiang Cancer Hospital — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Wenhua Yu

Conditions Nasopharyngeal Carcinoma; HLX43; anti-PD-L1 ADC