Testing HLX43 in Advanced Lung Cancer (Non-Small Cell): A Global Safety and Effectiveness Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Shanghai Henlius Biotech Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02]

Trial duration

16 Apr 2026 → ongoing

Decision date (initial)

2026-03-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Shanghai Henlius Biotech, Inc.

External identifiers

EU CT number

2025-523803-31-00

ClinicalTrials.gov

NCT06907615

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety, Therapy

To evaluate the clinical efficacy of HLX43 in advanced non-small cell lung cancer (NSCLC)

Secondary objectives 3

1. To evaluate the safety and tolerability of HLX43 in patients with advanced NSCLC
2. To evaluate the pharmacokinetic (PK) characteristics and immunogenicity of HLX43 in patients with advanced NSCLC
3. To investigate potential predictive or resistance biomarkers of HLX43 in the treatment of NSCLC

Conditions and MedDRA coding

Advanced non-small cell lung cancer (NSCLC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Have a full understanding of the study content, process, and possible adverse reactions before the study, and sign the informed consent form (ICF); voluntarily participate in the study; be able to complete the study as per protocol requirements
2. Aged ≥ 18 years at the time of signing the ICF, male or female
3. Histologically or cytologically confirmed, locally advanced (stage IIIB/IIIC) or metastatic (stage IV) NSCLC not suitable for radical treatment (complete surgical resection, concurrent/sequential radio-chemotherapy) according to the Union for International Cancer Control and the American Joint Committee on Cancer (AJCC) TNM staging system (8th edition), and should meet the following criteria: 1) Subjects without actionable genomic alterations (AGAs): • Subjects with non-squamous NSCLC must have documented negative test results for EGFR and ALK alterations. If no prior test results for EGFR and ALK are available, subjects must undergo EGFR and ALK testing at the study site. For subjects with squamous NSCLC, EGFR and/or ALK testing is not required prior to enrollment if their status is unknown; • No other known actionable genomic alterations, such as ROS1, NTRK, BRAF, MET exon 14 skipping, and RET; • Prior standard treatment failure of ≥ 1 line, including at least anti-PD-(L)1 antibody and platinum-based chemotherapy; 2) Subjects with AGAs: • Previous test results confirming the presence of one or more actionable genomic alterations; • Prior standard treatment failure of ≥ 1 line, including at least targeted therapy for driver gene alterations (patients with EGFR mutations must be previously treated with EGFR inhibitors) and platinum-based chemotherapy; Note: Definition of prior treatment failure with platinum-based chemotherapy: 1) Progressive disease following platinum-based chemotherapy in the recurrent or metastatic setting; 2) Progressive disease or recurrence during platinum-based chemotherapy, or within 6 months after the end of platinum-based chemotherapy during neoadjuvant chemotherapy, concurrent chemoradiotherapy, or adjuvant chemotherapy; 3) Intolerance to platinum-based chemotherapy
4. At least one measurable lesion as per RECIST 1.1 within 4 weeks prior to randomization; Note: Measurable target lesions should not be selected from previous radiotherapy sites or brain lesions. A measurable lesion within the field of local radiotherapy can be selected as the target lesion only when it is the only optional target lesion and the imaging evidence before and after progression should be available
5. Subjects who agree to provide archived tumor tissue specimens that meets the testing requirements (either from the most recent surgery or biopsy, preferably within 2 years) or agree to undergo a biopsy to collect tumor tissue for PD-L1 expression testing; Note: Formalin-fixed paraffin-embedded (FFPE) tumor samples (paraffin blocks or unstained sections, which must meet the quality control criteria for testing) collected from non-radiotherapy sites during the most recent surgery or biopsy at or after the diagnosis of malignant tumor and pathological reports of such specimens shall also be provided
6. The following conditions must be met in terms of the time of the first administration of the investigational product: at least 3 weeks (or 5 half-lives of the drug, whichever is shorter) from the previous major surgery, medical device treatment, locoregional radiotherapy (except for palliative radiotherapy for bone lesions), cytotoxic chemotherapy, immunotherapy, or biological product therapy; at least 2 weeks from the previous hormone therapy or small molecular targeted therapy; at least 1 week from the administration of the traditional Chinese medicine for anti-cancer indications or minor surgery; and recovery of treatment-induced AEs to Grade ≤ 1 (CTCAE v5.0, except for peripheral neurotoxicity and alopecia)
7. ECOG PS score of 0-1 within 1 week prior to randomization
8. Life expectancy > 3 months
9. Adequate organ functions as confirmed by laboratory tests within 1 week prior to randomization (no blood transfusions or treatment with granulocyte colony-stimulating factor is allowed within 14 days prior to the first dose
10. Male and female subjects with child-bearing potential must agree to use at least one highly effective contraception method during the study and within at least 8 months after the last dose of the investigational product; female subjects of childbearing age must be negative for pregnancy test within 7 days prior to enrollment.

Exclusion criteria 20

1. Histologically or cytologically confirmed tumor containing components of small cell lung cancer, neuroendocrine carcinoma, or sarcomatoid carcinoma
2. Prior treatment with any medication targeting topoisomerase I, including chemotherapy or ADCs
3. Radical radiation therapy within 3 months prior to the first dose
4. History of any second malignancy within 2 years prior to randomization, except for early-stage malignancies (carcinoma in situ or stage I tumors) that have received radical treatment, such as non-melanoma skin cancer, cervical carcinoma in situ, localized prostate cancer, ductal carcinoma in situ of the breast, and papillary thyroid carcinoma
5. History of adverse events leading to permanent discontinuation of immunotherapy, or occurrence of ≥ Grade 2 immune-related pneumonitis or myocarditis during prior immunotherapy
6. Presence of uncontrollable pleural effusion, pericardial effusion, or ascites requiring repeated drainage
7. Presence of spinal cord compression or clinically active metastases to central nervous system (referring to untreated or symptomatic metastases, or metastases requiring corticosteroids or anticonvulsants to control associated symptoms), carcinomatous meningitis. Subjects who have previously received treatment for brain metastases (such as whole brain radiotherapy or stereotactic brain radiotherapy) may be eligible, provided that they are clinically stable for at least 4 weeks with no imaging evidence of brain metastasis progression
8. Subjects with current or prior history of clinically significant pulmonary impairment due to pulmonary comorbidities, including but not limited to: any underlying lung disease (e.g., pulmonary embolism within 3 months prior to the first dose, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, interstitial pneumonia, pneumoconiosis, drug-related pneumonitis, and pleural effusion), any autoimmune, connective tissue, or inflammatory disease that may involve the lungs (i.e., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis), prior pneumonectomy that may interfere with the detection and management of suspected drug-related pulmonary toxicity, or history of radiation pneumonitis within 6 months
9. Patients with any poorly-controlled cardiovascular and cerebrovascular clinical symptoms or diseases, including but not limited to: (1) NYHA Class II or greater heart failure or left ventricular ejection fraction (LVEF) < 50%; (2) unstable angina pectoris; (3) myocardial infarction or cerebrovascular accident within 6 months (except lacunar infarction, slight cerebral ischemia, or transient ischemic attack); (4) poorly controlled arrhythmia (including QTc intervals ≥ 470 ms) (QTc intervals are calculated by Fridericia's formula); (5) poorly-controlled hypertension (systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg after active treatment)
10. Patients with active systemic infectious diseases requiring intravenous antibiotics within 2 weeks prior to randomization
11. Patients who have used moderate or potent CYP2D6 or CYP3A inhibitors or inducers within 2 weeks prior to randomization
12. Patients who have received systemic corticosteroids (prednisone > 10 mg/d or equivalent dose of similar drug) or other immunosuppressants within 2 weeks prior to randomization; Except: patients treated with topical, ocular, intra-articular, intranasal, and inhaled corticosteroids; short-term prophylactic use of corticosteroids for contrast agents, etc
13. Patients with known active or suspected autoimmune diseases. Patients with autoimmune-related hypothyroidism and receiving thyroid hormone replacement therapy and those with type 1 diabetes mellitus controlled with insulin therapy are eligible to be enrolled
14. Patients who have received live vaccine or live attenuated vaccine within 4 weeks prior to randomization
15. Patients who are known to have anaphylaxis to macromolecular protein preparations/monoclonal antibodies or are allergic to any component in the formulation of the investigational product
16. Patients with active tuberculosis
17. Patients with a history of immunodeficiency, including human immunodeficiency virus (HIV)-positive or other acquired or congenital immunodeficiencies, or history of organ transplantation
18. Patients with active HBV or HCV infection or HBV/HCV co-infection; Note: Patients who test positive for HBsAg or HBcAb during screening must further undergo HBV-DNA testing. If the test result suggests < 500 IU/mL, < 2500 copies/mL, or < ULN, the patient can be enrolled. Patients with HBV-DNA detected must agree to receive treatment with anti-HBV nucleos(t)ide analogues during the study. Patients who test positive for HCV antibody must further undergo HCV-RNA testing. If the test result suggests < ULN, the patient can be enrolled. Patients with HBV/HCV co-infection (positive for HBsAg or HBcAb and positive for HCV antibody) must be excluded
19. Pregnant or lactating women
20. Patients who are not suitable for participating in this clinical study due to any clinical or laboratory abnormalities or other reasons as assessed by the investigator

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective response rate (ORR) (assessed by the Blinded Independent Central Review [BICR] as per RECIST v1.1)

Secondary endpoints 9

1. Overall survival (OS)
2. Duration of response (DOR) and disease control rate (DCR) (assessed by the BICR and the investigator)
3. Adverse events (AEs), serious adverse events (SAEs), laboratory tests, vital signs, 12-lead ECG, and physical examination
4. Blood drug concentration and pharmacokinetics parameters of HLX43 at different doses (ADC, total antibody, and free small molecule toxin)
5. Positive rates of anti-HLX43 antibody (ADA) and neutralizing antibody (NAb)
6. Potential predictive or drug resistance biomarkers, such as PD-L1 expression levels, tumor-related gene mutations or expression levels, serum proteomic profiles
7. Quality of life assessment
8. Objective response rate (ORR) (assessed by investigator as per RECIST v1.1)
9. Progression-free survival (PFS) (assessed by the BICR and the investigator as per RECIST v1.1)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Shanghai Henlius Biotech Inc.

Sponsor organisation

Shanghai Henlius Biotech Inc.

Address

Building 1 Room 901 9th Floor, No 367 Shengrong Road, Shanghai Pilot Free Trade Zone No 367 Shengrong Road Shanghai Pilot Free Trade Zone

City

Shanghai

Postcode

201210

Country

China

Scientific contact point

Organisation

Shanghai Henlius Biotech Inc.

Contact name

Clinical Development

Public contact point

Organisation

Shanghai Henlius Biotech Inc.

Contact name

Clinical Development

Third parties 10

Locations

5 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 49 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications