A Phase I Clinical Study to Evaluate the Safety, Tolerability, and PK of HLX48 in Advanced/Metastatic Solid Tumors

A Phase I Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Characteristics of HLX48 (EGFR/c-MET Bispecific Antibody-Drug Conjugate) in Participants With Advanced/Metastatic Solid Tumors

This study is an open-label first-in-human phase I clinical study to evaluate the safety, tolerability, and pharmacokinetic characteristics of HLX48 in patients with advanced/metastatic solid tumors.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced/Metastatic Solid Tumors
• Intervention / Treatment: Drug: HLX48

Detailed Description

This study is an open-label first-in-human phase I clinical study to evaluate the safety and tolerability of HLX48 with escalated doses in the treatment of participants with advanced/metastatic solid tumors. In this study, a 3+3 dose escalation method will be adopted, and the participants will be administered HLX48 at different doses via intravenous infusion. The DLT observation period lasts for 3 weeks after the first dose of HLX48. To ensure the safety of participants, the Safety Review Committee (SRC) will review all safety data from all participants in the current cohort before deciding to proceed to the next cohort to include more participants. The SRC will review all safety data collected in the cohort to confirm that there are no unexpected, significant, or unacceptable risks to participants. Based on the evaluation results, the SRC will make recommendations on participant eligibility and dose levels, and vote on whether to start enrollment and treatment for the next cohort. If necessary, the investigator and the sponsor will discuss the need to add a new dose group based on the available data on safety, tolerability, PK, immunogenicity, and efficacy. If a participant withdraws from the study within the DLT observation period due to reasons other than therapeutic toxicity, he/she will be replaced by a new participant.

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ruihua Xu; Phone Number: 86-20-87343468; Email: Emailxurh@sysucc.org.cn

Study Locations

• China
  • Guangzhou
    • Guangzhou, Guangzhou, China, 716099
      • Sun Yat-sen University Cancer Center
      • Contact: SUN YAT-SEN UNIVERSITY CANCER CENTER; Phone Number: 86-20-87343468; Email: Emailxurh@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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 and ≤ 75 years at the time of signing the ICF, male or female;
3. Participants with histologically or cytologically confirmed advanced/metastatic malignant solid tumors, who have failed or have no available standard treatment;
4. At least one measurable lesion as per RECIST v1.1 within 4 weeks prior to the first dose;
5. An ECOG performance status score of 0-1 within 7 days prior to the first dose;
6. Expected survival > 3 months;
7. The following conditions should be met in terms of the time of the first dose of the investigational product: at least 28 days (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 14 days from the previous small molecule targeted drug therapy, hormone therapy, or administration of the traditional Chinese medicine for anti-tumor indications; at least 7 days from paracentesis and other minor surgery; recovery of treatment-induced AEs to Grade ≤ 1 (CTCAE v6.0, except for alopecia, well-controlled abnormal thyroid function and type 1 diabetes mellitus);
8. Availability of archival tumor tissue specimen (from the most recent surgery or biopsy, preferably within 2 years) meeting assay requirements, or agreement to undergo biopsy for tumor tissue collection for assessment of EGFR and c-MET protein expression;
9. Adequate organ function as confirmed by laboratory tests within 7 days prior to the first dose of the investigational product (no blood transfusions or treatment with granulocyte colony-stimulating factor within 14 days prior to the first dose);
10. For participants with hepatocellular carcinoma, Child-Pugh score must be A;
11. Male and female participants with reproductive 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 potential must receive pregnancy test within 7 days prior to enrollment to rule out pregnancy.

Exclusion Criteria:

1. History of other malignant tumors within 2 years prior to first dose, except radically treated early-stage malignant tumors (carcinoma in situ or stage I tumors), such as cured cervical carcinoma in situ, non-melanoma skin cancer, ductal carcinoma in situ of the breast, and papillary thyroid carcinoma;
2. History of serious ocular diseases, including: (1) keratoconjunctivitis sicca; (2) severe keratopathy; (3) moderate or severe xerophthalmia;
3. History of (non-infectious) interstitial lung disease (ILD) requiring use of steroids, or current ILD, or suspected ILD that cannot be ruled out by imaging at screening;
4. Known history of severe allergic reactions to macromolecular protein preparations/monoclonal antibodies, or allergy to any component in the formulation of the investigational product; previous exposure to ADCs with topoisomerase I inhibitors as payload;
5. Active systemic infectious diseases requiring intravenous antibiotics within 2 weeks prior to the first dose of the investigational product;
6. 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.;
7. 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); (6) pericarditis or uncontrolled pericardial effusion; (7) myocarditis;
8. Assessed as unsuitable for inclusion by the investigator, due to newly developed or clinically symptomatic brain or meningeal metastases, spinal cord compression, or cancerous meningitis, or uncontrolled brain or spinal cord metastases that have been evidenced;
9. Participants with known active or suspected autoimmune diseases. Participants 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;
10. Presence of unhealed skin lesions, including but not limited to (1) major traumatic injury within 4 weeks prior to the first dose (for paracentesis and other minor surgery, the investigator must confirm that the skin has healed prior to the first dose); (2) planned major surgery during treatment with the investigational product or within 6 months after the last dose;
11. Presence of uncontrollable pleural effusion or pericardial effusion after appropriate intervention, or ascites requiring repeated drainage (once a month or more frequently);
12. Use of strong inhibitors or inducers of CYP3A within 2 weeks prior to the first dose;
13. Patients with active tuberculosis;
14. Patients with a history of immunodeficiency, including human immunodeficiency virus (HIV)-positive or other acquired or congenital immunodeficiencies, or a history of organ transplantation;
15. Patients with active HBV or HCV infection or HBV/HCV co-infection;
16. Pregnant or lactating women;
17. Participants 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; A total of six dose escalations were preset: Dose1, Dose2, Dose3, Dose4, Dose5, Dose6.	Drug: HLX48; EGFR/c-MET Bispecific Antibody-Drug Conjugate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Dose-Limiting Toxicity (DLT) of HLX48 within 21 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 21 days after the first administration of HLX48.	From first dose to the end of Cycle 1 (each cycle is 3 weeks)
The maximum tolerated dose (MTD) of HLX48	The highest dose level, at which DLT is observed in no more than one of 6 evaluable patients, is defined as MTD of HLX48	From first dose to the end of Cycle 1 (each cycle is 3 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Percentage of participants with complete response (CR) and partial response (PR) based on investigator assessment.	approximately up to 24 months
Duration of response (DOR)	Length of time response continued based on investigator's assessment.	approximately up to 24 months.
Overall survival (OS)	Time from the date of enrollment to the date of death for any cause.	approximately up to 24 months
Progression-free survival (PFS)	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.	approximately up to 24 months.
Cmax	Maximum serum concentration (Cmax) of HLX48.	Up to 21 days after the first dose
Tmax	Time to maximum serum concentration (Tmax) of HLX48.	Up to 21 days after the first dose
T1/2	Half-life (T1/2) of HLX48.	Up to 21 days after the first dose
ADA (anti-drug antibody)	Incidence and titer of ADA of HLX48.	approximately up to 24 months
Nab (neutralizing antibody)	Incidence and titer of Nab of HLX48.	approximately up to 24 months

Collaborators and Investigators

• Sponsor: Shanghai Henlius Biotech

Study record dates

Study Major Dates

• Study Start (Estimated): May 17, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: March 11, 2026
• First Submitted That Met QC Criteria: March 11, 2026
• First Posted (Actual): March 16, 2026

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: HLX48-FIH101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No