A Phase I Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of HLX3901 in Patients With Advanced SCLC or NEC

NCT07416695 | Recruiting Phase 1

• 1 other identifier: HLX3901-FIH101
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 2

Brief Summary

This study is an open-label first-in-human phase I clinical study to evaluate the safety, tolerability, and pharmacokinetic characteristics of HLX3901 in patients with Advanced Small Cell Lung Cancer or Neuroendocrine Carcinoma.

Conditions

SCLC; NEC

Outcome Measures

Primary Outcomes (4)

• The Dose-Limiting Toxicity (DLT) of HLX3901 within 28 days after the first Administration

  DLT refers to the AEs that are determined to be related to the investigational product by the investigator, whose severity will affect the escalation of dose level. In this study, the DLT observation period lasts for 28 days after the first administration of HLX3901.

  From first dose to the end of Cycle 1 (each cycle is 4 weeks)

• The maximum tolerated dose (MTD) of HLX3901

  The highest dose level, at which DLT is observed in no more than one of 6 evaluable patients, is defined as MTD of HLX3901

  From first dose to the end of Cycle 1 (each cycle is 4 weeks)

• RP2D

  The recommended phase 2 dose of HLX3901

  approximately up to 24 months

• Objective response rate (ORR)

  Percentage of participants with complete response (CR) and partial response (PR) based on investigator assessment.

  approximately up to 24 months

Secondary Outcomes (5)

• Number of participants with adverse events (AEs)

  Up to approximately 2 years

• Number of participants with serious adverse events (SAEs)

  Up to approximately 2 years

• Duration of response (DOR)

  Up to approximately 2 years

• Progression-free survival (PFS)

  approximately up to 24 months

• Overall survival (OS)

  approximately up to 24 months

Study Arms (2)

Phase Ia：Dose Escalation and Backfill

EXPERIMENTAL

A total of seven dose escalations were preset: Dose1, Dose2, Dose3, Dose4, Dose5, Dose6, and Dose7. The backfill cohort will enrolls 2 to 3 dose groups.

Drug: HLX3901

Experimental: Phase Ib：Dose Expansion

EXPERIMENTAL

Participants will receive the RP2D identified in Dose Escalation Study .

Drug: HLX3901

Interventions

HLX3901 DRUG

• HLX3901 will be administered as an intravenous (IV) infusion.

Experimental: Phase Ib：Dose Expansion; Phase Ia：Dose Escalation and Backfill

Eligibility Criteria

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

You may qualify if:

• 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;
• Aged ≥ 18 years and ≤ 75 years at the time of signing the ICF, male or female;
• Histologically or cytologically confirmed advanced small cell lung cancer or neuroendocrine carcinoma; patients with advanced small cell lung cancer must have experienced intolerance, recurrence, or disease progression following prior treatment with a platinum-based therapy combined with immune checkpoint inhibitors, while patients with neuroendocrine carcinoma must have experienced intolerance, recurrence, or disease progression following prior platinum-based therapy; allowed histological subtypes include combined small cell lung cancer and mixed neuroendocrine-non-neuroendocrine neoplasms.
• At least one measurable lesion as per RECIST 1.1 within 4 weeks prior to the first administration;
• An ECOG performance status score of 0-1 within 7 days prior to the first administration;
• Expected survival \> 3 months;
• The following conditions must be met in terms of the time of the first administration of the investigational product: at least 28 days 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 14 days from the previous small molecule targeted drug therapy and previous hormone therapy; at least 7 days from the previous administration of the traditional Chinese medicine for anti-tumor indications or minor surgery; recovery of treatment-induced AEs to Grade ≤ 1 (CTCAE v6.0, except for alopecia);
• Participants who agree to provide archived tumor tissue specimens that meet 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 DLL3 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.
• Adequate organ function as confirmed by laboratory tests within 7 days prior to the first administration of the investigational product, with no therapies such as blood transfusion, albumin infusion, renal replacement therapy, granulocyte colony-stimulating factor (G-CSF), thrombopoietin, or erythropoietin administered within 14 days prior to the first administration:
• Male and female participants with child-bearing potential must agree to use at least one highly effective contraception method during the study and within at least 6 months after the last dose of the investigational product; female participants of childbearing age must be negative for pregnancy test within 7 days prior to enrollment.

You may not qualify if:

• History of other malignant tumors within 2 years prior to the first administration, except cured cervical carcinoma in situ or cutaneous basal cell carcinoma;
• Presence of Grade ≥ 2 immune-related pneumonitis or immune-related myocarditis, or severe, life-threatening immune-mediated AEs or infusion-related reactions, including those leading to permanent discontinuation, when receiving previous anti-tumor immunotherapy;
• History or presence of clinically significant pulmonary impairment due to concurrent lung disease, including but not limited to any underlying lung disease (e.g., pulmonary embolism within 3 months prior to the first administration, severe asthma, severe chronic obstructive pulmonary disease, restrictive pulmonary 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, Sicca syndrome, and sarcoidosis), prior pneumonectomy that may interfere with the detection and management of suspected drug-related pulmonary toxicity, or history of radiation pneumonitis within the past 6 months;
• With central nervous system diseases within 12 months prior to enrollment, such as seizures, cerebral hemorrhage, paralysis, aphasia, cerebral infarction (except for old cerebral infarction), severe brain injury, dementia, Parkinson's disease, cerebellar disease, mental illness, or any autoimmune disease involving the central nervous system;
• Active paraneoplastic syndrome;
• History of hypophysitis or pituitary dysfunction;
• Presence of uncontrolled third-space effusions (e.g., massive pleural effusion, ascites, or pericardial effusion) requiring repeated drainage and considered by the investigator to be unsuitable for enrollment;
• Prior allogeneic stem cell or solid organ transplantation;
• Prior exposure to any of the following: (1) combination or sequential therapy targeting DLL3, CD3, or CD28; (2) treatment with antibody-drug conjugates (ADCs); (3) major surgery, chemotherapy, biologic therapy, endocrine therapy, or macromolecular targeted therapy within 4 weeks prior to the first administration. Traditional Chinese medicine and small molecule targeted therapy with anti-tumor indications ≤ 2 weeks from the first administration of the investigational product;
• Known history of severe allergic reactions, anaphylactoid reactions, or other hypersensitivity reactions to humanized antibodies or fusion proteins, severe allergic reactions to macromolecular protein preparations/monoclonal antibodies, or allergy to components of the investigational product preparations;
• Active systemic infectious diseases requiring intravenous antibiotics within 2 weeks prior to the first administration of the investigational product;
• 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 ≥ 450 ms for males and ≥ 470 ms for females) (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);
• Active central nervous system (CNS) metastases and/or carcinomatous meningitis known or diagnosed at screening. However, the following participants are allowed to be enrolled: 1) Patients with asymptomatic brain metastases (i.e., no progressive central nervous system symptoms caused by brain metastases, no requirement for corticosteroids, and lesion size ≤ 1.5 cm) may be included, but are required to receive regular brain imaging as a site of disease. 2) Participants with treated brain metastases that have been stable for at least 2 months (confirmed by 2 imaging assessments at least 4 weeks apart following brain metastasis treatment), with no evidence of new or enlarging brain metastases and discontinued steroids at least 3 days prior to administration (stable brain metastases here should be confirmed before the first administration of the investigational product).
• Patients with known active or suspected autoimmune diseases. Patients with autoimmune-related hypothyroidism who are receiving thyroid hormone replacement therapy and those with type 1 diabetes mellitus controlled with insulin therapy are eligible to be enrolled;
• Patients who have received systemic corticosteroids (prednisone \> 10 mg/day or equivalent dose of a similar drug) or other immunosuppressive agents within 14 days prior to the first administration; Except: patients treated with topical, ocular, intra-articular, intranasal, and inhaled corticosteroids; those with short-term use of corticosteroids for prophylaxis if a contrast agent is used;

Sponsors & Collaborators

• Shanghai Henlius Biotech: lead

Study Sites (2)

Peking Union Medical College Hospital

Beijing, China

RECRUITING

Shanghai Chest Hospital

Shanghai, China

NOT YET RECRUITING

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2026
• First Posted: February 18, 2026
• Study Start: April 17, 2026
• Primary Completion (Estimated): May 30, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: July 8, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)