A Phase I Study to Evaluate the Safety, Tolerability, and PK of HLX43 in Advanced/Metastatic Solid Tumors

Phase 1

Recruiting

• Conditions: Advanced Solid Tumor
• Interventions: Drug: HLX43

• Registration Number: NCT06115642
• Lead Sponsor: Shanghai Henlius Biotech

Brief Summary

This study is an open-label first-in-human phase I clinical study to evaluate the safety and tolerability of HLX43.

Detailed Description

This study is an open-label first-in-human phase I clinical study to evaluate the safety and tolerability of HLX43 with escalated doses in the treatment of patients with advanced/metastatic solid tumors. In this study, a 3 + 3 dose escalation method will be adopted, and the patients will be administered with HLX43 at different doses via intravenous infusion. The DLT observation period lasts for 3 weeks after the first administration of HLX43.

Study Timeline

• Study First Submitted: 2023-10-30
• Study First Submitted QC: 2023-10-30
• Study First Posted: 2023-11-03
• Study Start: 2023-11-24
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-12
• Last Update Posted: 2025-05-15
• Primary Completion: 2026-06-30
• Study Completion: 2027-11-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

1. Have a full understanding of the study content, process, and possible adverse reactions before the study, and sign the ICF; voluntarily participate in the study; be able to complete the study as per protocol requirements;
2. ≥ 18 years and ≤ 75 years at the time of signing the ICF, male or female;
3. Patients with histologically or cytologically confirmed advanced/metastatic malignant solid tumors, who are refractory to or intolerable with standard treatment, or for which no standard treatment is available;
4. At least one measurable lesion as per RECIST 1.1 within 4 weeks prior to the first administration;
5. An ECOG performance status score of 0-1 within 7 days prior to the first administration;
6. Life expectancy > 3 months;
7. 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 molecular targeted therapy; at least 14 days from the previous hormone therapy, administration of the traditional Chinese medicine for anti-tumor indications, or minor surgery; and recovery of treatment-induced AEs to grade ≤ 1 (CTCAE v5.0, except for alopecia);
8. Subjects 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 PD-L1 and DDX5 expression testing;
9. Adequate organ functions as confirmed by laboratory tests within 7 days prior to the first administration of the investigational product (no blood transfusions or treatment with granulocyte colony-stimulating factor within 14 days prior to the first administration)
10. For patients with hepatocellular carcinoma, Child-Pugh score must be A;
11. 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 6 months after the last administration of the investigational product; female subjects of childbearing age must have a negative pregnancy test within 7 days prior to enrollment.

Exclusion Criteria

1. Patients who have history of other malignant tumors within 2 years prior to the first administration, except for cured cervical carcinoma in situ or cutaneous basal cell carcinoma;
2. Patients who previously have grade ≥ 3 irAEs in immunotherapy;
3. Patients who have history of (non-infectious) ILD requiring steroids, current ILD, or suspected ILD that cannot be ruled out by imaging at screening;
4. Subjects who are known to have severe anaphylaxis to protein preparations/ monoclonal antibodies or are allergic to any component in the formulation of the investigational product;
5. Patients who have active systemic infectious diseases requiring intravenous antibiotics within 2 weeks prior to the first administration of the investigational product;
6. Subjects who have any poorly-controlled cardiovascular and cerebrovascular clinical symptoms or diseases, including but not limited to: (1) NYHA Class II or greater heart failure or LVEF < 50%; (2) unstable angina pectoris; (3) myocardial infarction or cerebrovascular accident within 6 months (except for 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);
7. Patients who have been assessed as unsuitable for inclusion by the investigator, due to brain metastases, spinal cord compression, or cancerous meningitis with clinical symptoms, or uncontrolled brain or spinal cord metastases that have been evidenced; Note: Patients with asymptomatic or stable brain metastases, spinal cord compression, or cancerous meningitis as judged by the investigator are allowed to be enrolled.
8. Patients with known active or suspected autoimmune diseases. Those with autoimmune-related hypothyroidism and receiving thyroid hormone replacement therapy and those with type 1 diabetes mellitus controlled with insulin therapy are allowed to be enrolled;
9. Patients who have received systemic corticosteroids (prednisone > 10 mg/day or an 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;
10. Patients who have used potent CYP2D6/CYP3A inhibitors or inducers within 2 weeks prior to the first administration;
11. Patients with active tuberculosis;
12. Patients who have history of immunodeficiency, including HIV infection or other acquired or congenital immunodeficiencies, or history of organ transplantation;
13. Patients with active HBV or HCV infection or HBV/HCV co-infection;
14. Patients who have received live vaccines within 28 days prior to the first administration;
15. Pregnant or lactating women;
16. Subjects 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HLX43 group	HLX43	Patients with good tolerability and well controlled disease will receive the treatment once every 3 weeks (Q3W), until progressive disease (PD) without any clinical benefit, initiation of other anti-tumor therapies, death, intolerable toxicity, or withdraw the informed consent (whichever occurs first).

Primary Outcome Measures

Name	Time	Method
The Dose-Limiting Toxicity (DLT) of HLX43 within 21 days after the first Administration	From first dose to the end of Cycle 1 (each cycle is 3 weeks)	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 21 days after the first administration of HLX43.
The maximum tolerated dose (MTD) of HLX43	From first dose to the end of Cycle 1 (each cycle is 3 weeks)	The highest dose level, at which DLT is observed in no more than one of 6 evaluable patients, is defined as MTD of HLX43

Secondary Outcome Measures

Name	Time	Method
Objective response rate (ORR)	approximately up to 24 months	Percentage of participants with complete response (CR) and partial response (PR) based on investigator assessment.
Duration of response (DOR)	approximately up to 24 months.	Length of time response continued based on investigator's assessment.
Progression-free survival (PFS)	approximately up to 24 months	The PFS is defined as the time from the date of enrollment to the date of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause,whichever occurred first.
Overall survival (OS)	approximately up to 24 months	Time from the date of enrollment to the date of death for any cause.
Cmax	Up to 21 days after the first dose	Maximum serum concentration (Cmax) of HLX43.
Tmax	Up to 21 days after the first dose	Time to maximum serum concentration (Tmax) of HLX43.
T1/2	Up to 21 days after the first dose	Half-life (T1/2) of HLX43.
ADA (anti-drug antibody)	approximately up to 24 months	Incidence and titer of ADA of HLX43.
Nab (neutralizing antibody)	approximately up to 24 months	Incidence and titer of Nab of HLX43.
Number of subjects experiencing adverse events	Day 1 through 90 days after last dose.	Frequency and seriousness of treatment emergent adverse events (TEAEs).

Trial Locations

Locations (2)

Cancer Hospital, Chinese Academy of Medical Sciences; 🇨🇳 Beijing, Beijing, China

Xiangya Hospital Central South University; 🇨🇳 Changsha, Hunan, China