A Phase I Study to Evaluate the Safety, Tolerability, and PK of HLX37 in Advanced/Metastatic Solid Tumors

NCT ID: NCT07274813

Last Updated: 2025-12-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 254 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-11-28
• Study Completion Date: 2028-12-30

Brief Summary

This study is an open-label first-in-human phase I clinical study to evaluate the safety, tolerability, and pharmacokinetic characteristics of HLX37 in patients with advanced/metastatic solid tumors.

Detailed Description

This study is an open-label first-in-human phase I clinical study to evaluate the safety, tolerability , and pharmacokinetic characteristics of HLX37 with escalated doses in the treatment of patients with advanced/metastatic solid tumors.

In Phase Ia Part 1of this study, a 3 + 3 dose escalation method will be adopted, and the patients will be administered with HLX37 at different doses via intravenous infusion. The DLT observation period lasts for 3 weeks after the first administration of HLX37.

After the DLT observation period of the single-drug ramp-up 20mg/kg dose group ended and the SRC safety assessment was conducted, that is Initiate the Phase Ia Part2 of this study to conduct HLX37 in patients with advanced non-small cell lung cancerThe dosage of combined chemotherapy is increasing. The 3+3 dose escalation method will be adopted, and the subjects will receive different doses. Intravenous infusion administration of HLX37 in combination with chemotherapy (tentatively 10 mg/kg, 20 mg/kg, 30 mg/kg) Or other doses of HLX37 combined with chemotherapy, administered intravenously at Q3W. DLT observation period 3 weeks after the first administration of HLX37 in combination with chemotherapy.

In phase Ib of this study, The Safety Review Committee will recommend dose groups for expansion based on the safety, efficacy and PK data of the dose escalation phase.

Conditions

Advanced/Metastatic Solid Tumors; NSCLC

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Ia (Dose Escalation)

Patients with advanced/metastatic solid tumors

Group Type: EXPERIMENTAL

HLX37-Dose1

Intervention Type: DRUG

Patients with advanced/metastatic solid tumors

HLX37-Dose2

Intervention Type: DRUG

5mg/kg Q3W

HLX37-Dose3

Intervention Type: DRUG

10mg/kg Q3W

HLX37-Dose4

Intervention Type: DRUG

20mg/kg Q3W

Interventions

HLX37-Dose1

Patients with advanced/metastatic solid tumors

Intervention Type: DRUG

HLX37-Dose2

5mg/kg Q3W

Intervention Type: DRUG

HLX37-Dose3

10mg/kg Q3W

Intervention Type: DRUG

HLX37-Dose4

20mg/kg Q3W

Intervention Type: DRUG

Eligibility Criteria

Exclusion Criteria

Subjects who meet any of the following criteria will not be eligible for this study:

1. There should be a history of other malignant tumors within 3 years prior to the first medication, except for cured cervical carcinoma in situ or basal cell carcinoma of the skin.

2. There have been adverse events in the past that led to the permanent termination of immunotherapy; Or there was a history of grade ≥2 immune-related pneumonia or immune-related myocarditis;

3. Has a history of (non-infectious) interstitial lung disease (ILD), and currently still requires steroid drug treatment; Or currently having active ILD, or suspected through imaging researchers at the time of screening that there is a risk of ILD aggravation or that they are not suitable to participate in this study;

4. It is known that the subject has had a severe allergic reaction to macromolecular protein preparations/monoclonal antibodies in the past, or is allergic to the components of the test drug preparation;

5. Within two weeks before the first medication, there is an active systemic infectious disease that requires intravenous antibiotic treatment;

6. The subjects have poorly controlled clinical symptoms or diseases of the cardiovascular and cerebrovascular system, including but not limited to: (1) NYHA grade II or above heart failure or left ventricular ejection fraction (LVEF) < 50%; (2) Unstable angina pectoris; (3) Has experienced myocardial infarction or cerebrovascular accident within 6 months (excluding lacunar infarction, mild cerebral ischemia or transient ischemic attack); (4) Poorly controlled arrhythmias (including QTc intervals of ≥ 450 ms in men and ≥ 470 ms in women) (QTc intervals are calculated using the Fridericia formula);

7. Subjects who had experienced the following diseases within 12 months prior to the first administration: a history of lower esophageal varices, severe ulcers, unhealed wounds, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, abdominal abscess or a history of acute gastrointestinal bleeding; Subjects who have experienced the following diseases within 6 months prior to the first administration: any arterial thromboembolic event, NCI CTCAE V.5.0 grade 3 or higher venous thromboembolism, transient ischemic attack, cerebrovascular accident, hypertensive crisis or history of hypertensive encephalopathy, subjects with history of acute exacerbation of chronic obstructive pulmonary disease; Patients currently suffering from hypertension with a systolic blood pressure of ≥160 MMHG or a diastolic blood pressure of ≥100 MMHG after oral antihypertensive drug treatment.

8. Known to have meningeal metastasis, or uncontrolled or symptomatic central nervous system (CNS) metastasis, manifested as clinical symptoms, cerebral edema, spinal cord compression and/or progressive growth. Subjects with a history of central nervous system metastasis or spinal cord compression who have clearly received treatment and have been determined by the investigator to have stable clinical manifestations after discontinuing anticonvulsants and steroids for 8 weeks before the start of the study treatment can be enrolled in the study. Untreated, asymptomatic subjects with brain metastases (i.e., those without neurological symptoms, no need for corticosteroid hormones, no long diameter of any brain metastases >1.5 cm, and no obvious edema around the brain metastases) can be enrolled. Brain metastases are not regarded as target lesions.

9. There is a known active or suspected autoimmune disease. However, subjects with autoimmune hypothyroidism who have received thyroid hormone replacement therapy are allowed to participate in the study; Allow controlled type 1 diabetes subjects receiving insulin treatment to participate in the study;

Subjects who have received systemic corticosteroids (prednisone > 10mg/ day or equivalent doses of similar drugs) or other immunosuppressants within 14 days prior to the first administration; Except for the following situations: treatment with topical, ocular, intra-articular, intranasal and inhaled corticosteroids; Short-term use of corticosteroids for preventive treatment in cases such as contrast agents;

11. Suffering from active pulmonary tuberculosis;

12. Subjects with a history of severe bleeding tendencies or coagulation disorders; Subjects with clinically significant bleeding symptoms within one month before the first administration, including but not limited to gastrointestinal bleeding, hemoptysis (defined as coughing up or expelling ≥1 teaspoon of fresh blood or small blood clots, or only coughing up blood without sputum; those with sputum blood can be included), and epistaxis (excluding epistaxis and bloody reflux mucus); Subjects whose imaging examinations during screening showed that the tumor surrounded important blood vessels or had obvious necrosis and cavities, and the researchers judged that there was a risk of bleeding in participating in the study; Patients with central and cavitary squamous non-small cell lung cancer (according to the researchers' judgment, such patients have a higher risk of bleeding).

13. Currently using or having used aspirin (> 325mg/ day) or dipyridamole, clopidine, clopidogrel and cilostazole for treatment within 7 days before the first use.

14. Currently in use or under study, full-dose oral or injectable anticoagulant drugs or thrombolytic drugs have been used for therapeutic purposes within 7 days prior to the first administration. Prophylactic anticoagulant therapy is permitted for open intravenous infusion systems, provided that the drug activity is less than 1.5 times the upper limit of normal for the international normalized ratio (INR) and the partial thromboplastin time (APTT) is within the normal range within 14 days prior to the first administration. Prophylactic use of low-molecular-weight heparin (i.e. Enoxaparin 40mg/ day) is permitted.

15. Daily administration of non-steroidal anti-inflammatory drugs is required for long-term treatment. Occasional use of NSAIDs is permitted to relieve medical symptoms such as headache or fever 16. In the past, when receiving anti-angiogenic therapy, grade ≥3 toxicity related to anti-angiogenic therapy occurred (except for toxicity such as fever that the researchers considered not to pose a safety risk to the subjects).

17. Have a history of immune deficiency, including a positive test for the human immunodeficiency virus (HIV), or suffer from other acquired or congenital immune deficiency diseases, or have a history of organ transplantation; 18. Active HBV or HCV infection or co-infection: If HBsAg (+) and/or HBcAb (+), HBV-DNA testing is required. The result must be less than 500 IU/mL or less than 2500 copies/mL or less than the upper limit of normal (ULN) for enrollment. For eligible subjects, if HBV-DNA can be detected, it is recommended that they receive nucleoside anti-hepatitis B virus treatment. If the HCV antibody is (+), HCV-RNA must be tested, and the result must be less than the upper limit of normal value (ULN) for enrollment. Subjects with co-infection of hepatitis B and C should be excluded (with positive HBsAg or HBcAb tests and positive HCV antibody tests).

19. Have received a live vaccine within 28 days prior to the first administration; 20. Pregnant or lactating women; 21. The researcher believes that the subjects have any clinical or laboratory test abnormalities or other reasons that make them unsuitable to participate in this clinical study.

22. Suffering from local or systemic diseases not caused by malignant diseases; Or diseases or symptoms caused by tumors that may lead to higher medical risks and/or uncertain survival assessment results, such as neoplastic leukemia-like reactions (white blood cell count > 20×109/L), cachexia manifestations (for example, known weight loss of more than 10% within 3 months before screening), etc.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Henlius Biotech

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Shanghai Chest Hospital

Shanghai, , China

The Second Affiliated Hospital of Air Force Medical University of the People's Liberation Army of China

Xi'an, , China

Countries

China

Other Identifiers

HLX37- FIH101

Identifier Type: -

Identifier Source: org_study_id