A Phase II Clinical Study to Evaluate HLX43 in Combination With Serplulimab in Subjects With Advanced Lung Cancer

NCT07253142 | Not Yet Recruiting Phase 2

• 1 other identifier: HLX43-NSCLC202
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The study is to explore the the reasonable dosage and to evaluate the efficacy, safety and tolerability of HLX43 (Anti-PD-L1 ADC) in combination with Serplulimab (anti-PD-1 humanized monoclonal antibody injection) in patients with advanced lung cancer.

Conditions

Non Small Cell Lung Cancer; Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• ORR

  Objective response rate (ORR) is the proportion of subjects with the best overall response being CR or PR (assessed by investigator per RECIST v1.1)

  up to 24 week

Secondary Outcomes (5)

• PFS

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months

• ORR

  Up to 24 weeks

• PFS

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months

• OS

  From randomization to death from any cause (up to approximately 18 months)

• Incidence and severity of adverse events (AEs)

  time from the date of the first dose of study drug until 90 days after last dose, assessed up to 18 months

Study Arms (2)

HLX43 dose 1

EXPERIMENTAL

Patients with good tolerability and well controlled disease will receive the treatment once every 3 weeks (Q3W), until disease progression, initiation of a new anti-tumor therapy, death, emergence of intolerable toxicity, or withdrawal of informed consent (whichever occurs first).

Drug: HLX43 dose 1

HLX43 dose 2

EXPERIMENTAL

Patients with good tolerability and well controlled disease will receive the treatment once every 3 weeks (Q3W), Until disease progression, initiation of a new anti-tumor therapy, death, emergence of intolerable toxicity, or withdrawal of informed consent (whichever occurs first)

Drug: HLX43 dose 2

Interventions

HLX43 dose 1 DRUG

HLX43 is an anti-PD-L1 monoclonal antibody conjugated with a novel high potency DNA topoisomerase I (topo I) inhibitor, with a drug-antibody-ratio (DAR) of 8.

Also known as: Serplulimab

HLX43 dose 1

HLX43 dose 2 DRUG

HLX43 is an anti-PD-L1 monoclonal antibody conjugated with a novel high potency DNA topoisomerase I (topo I) inhibitor, with a drug-antibody-ratio (DAR) of 8.

Also known as: Serplulimab

HLX43 dose 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Voluntarily to participate in the trial, and be able to complete the study as required by the protocol;
• \. Age ≥18 years and ≤75 years;
• \. Histologically or cytologically confirmed locally advanced (stage IIIB/IIIC) or metastatic (stage IV) NSCLC unsuitable for radical treatment without actionable gene alteration (AGA); or Histologically or cytologically confirmed SCLC unsuitable for radical treatment, with evidence of disease progression or recurrence;
• \. Subjects must meet the following prior treatment requirements:
• Have received platinum-based chemotherapy combined with anti-PD-1/L1 monoclonal or bispecific antibodies as prior first-line treatment; have received no more than second-line treatment; or
• Have received platinum-based chemotherapy and anti-PD-1/L1 monoclonal or bispecific antibodies (in any sequence) as sequential treatment; have received no more than third-line treatment;
• \. Within 4 weeks prior to randomization, have at least one measurable lesion according to RECIST 1.1 efficacy evaluation criteria;
• \. Subjects agree to provide archived tumor tissue samples (from the most recent surgery or biopsy, preferably within 2 years) that meet testing requirements or agree to undergo a biopsy to collect tumor tissue for PD-L1 expression testing;
• \. Before the first administration of the investigational drug, there must be at least a 3-week interval or 5 half-lives of the drug (whichever is shorter) from prior major surgical procedures, device therapy, local radiotherapy (excluding palliative radiotherapy for bone lesions), cytotoxic chemotherapy, immunotherapy, or biological therapy. There must be at least a 2-week interval from prior hormone therapy or small molecule targeted therapy, and at least a 1-week interval from traditional Chinese medicine with anti-tumor indications or minor surgical procedures. Adverse events caused by prior treatment must have recovered to CTCAE v5.0 ≤ grade 1 (excluding grade 2 peripheral neurotoxicity and alopecia);
• \. ECOG performance status score of 0-1 within one week prior to randomization;
• \. Expected survival time of more than 3 months;
• \. Laboratory tests within one week prior to randomization confirm adequate organ function (within 14 days before the first administration, without receiving treatments such as transfusion, granulocyte colony-stimulating factor, thrombopoietin, or erythropoietin);
• \. Male and female subjects with reproductive potential must agree to use at least one highly effective contraceptive method during the trial and for at least 6 months after the last administration of the investigational drug. Female subjects of childbearing potential must have a negative pregnancy test within 7 days prior to enrollment.

You may not qualify if:

• \. Mixed SCLC, mixed NSCLC, or sarcomatoid carcinoma components confirmed by tumor histology or cytology;
• \. Imaging suggests tumor invasion of major blood vessels or important organs, or the presence of a risk of esophago-tracheal fistula or esophagopleural fistula;
• \. Previously received any drug therapy targeting topoisomerase I, including chemotherapy or ADC drugs;
• \. Received radical radiotherapy within 3 months prior to the first dose;
• \. History of any second malignancy within 2 years prior to randomization, except for early-stage malignancies treated with radical therapy (carcinoma in situ or stage I tumors), such as non-melanoma skin cancer, cervical carcinoma in situ, localized prostate cancer, ductal carcinoma in situ of the breast, or papillary thyroid carcinoma;
• \. History of adverse events leading to permanent discontinuation of immunotherapy, or a history of ≥ grade 2 immune-related pneumonitis or immune-related myocarditis;
• \. Presence of uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
• \. Presence of spinal cord compression or clinically active central nervous system metastases (referring to untreated or symptomatic metastases, or metastases requiring corticosteroids or anticonvulsants to control related symptoms), or meningitis carcinomatosa. Subjects who have previously received treatment for brain metastases (e.g., whole-brain radiotherapy or stereotactic brain radiotherapy) may participate in the study, provided they have been clinically stable for at least 4 weeks with no imaging evidence of brain metastasis progression;
• \. History or current presence of clinically severe lung impairment caused by pulmonary diseases, including but not limited to any underlying pulmonary disease (e.g., pulmonary embolism, severe asthma, severe chronic obstructive pulmonary disease, restrictive pulmonary disease, interstitial pneumonia, pneumoconiosis, drug-related pneumonia, pleural effusion, etc., within 3 months prior to the first dose) or any autoimmune, connective tissue, or inflammatory diseases potentially involving the lungs (e.g., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), or subjects who have undergone pneumonectomy, which may interfere with the detection and management of suspected drug-related pulmonary toxicity; subjects with radiation pneumonitis within 6 months;
• \. Subjects with poorly controlled cardiovascular or cerebrovascular clinical symptoms or diseases;
• \. Presence of active systemic infectious diseases requiring intravenous antibiotic therapy within 2 weeks prior to randomization;
• \. Use of moderate or strong CYP2D6 or CYP3A inhibitors or inducers within 2 weeks prior to randomization;
• \. Patients who received systemic corticosteroids (prednisone \>10mg/day or equivalent doses of similar drugs) or other immunosuppressive therapy within 2 weeks prior to randomization;
• \. Presence of known active or suspected autoimmune diseases. However, patients with autoimmune-related hypothyroidism receiving thyroid hormone replacement therapy are allowed to participate in the study; patients with controlled type 1 diabetes receiving insulin therapy are allowed to participate in the study;
• \. Received live or attenuated live vaccines within 4 weeks prior to randomization;

Sponsors & Collaborators

• Shanghai Henlius Biotech: lead

Study Sites (1)

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Yongqing Lin

CONTACT

18925185148; yongqing_lin@henlius.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2025
• First Posted: November 28, 2025
• Study Start: January 14, 2026
• Primary Completion (Estimated): June 18, 2027
• Study Completion (Estimated): June 19, 2028
• Last Updated: December 2, 2025

Record last verified: 2025-12

Locations

CN (1)