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

NCT07473726 | Recruiting Phase 1

• 1 other identifier: HLX48-FIH101
• Study Type: interventional
• Target: 72
• Locations: 2 countries
• Sites: 7

Brief Summary

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.

Conditions

Advanced/Metastatic Solid Tumors

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• Objective response rate (ORR)

  approximately up to 24 months

• Duration of response (DOR)

  approximately up to 24 months.

• Progression-free survival (PFS)

  approximately up to 24 months.

• Overall survival (OS)

  approximately up to 24 months

• Cmax

  Up to 21 days after the first dose

Study Arms (1)

Dose Escalation

EXPERIMENTAL

A total of six dose escalations were preset: Dose1, Dose2, Dose3, Dose4, Dose5, Dose6.

Drug: HLX48

Interventions

HLX48 DRUG

EGFR/c-MET Bispecific Antibody-Drug Conjugate

Dose Escalation

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;
• Participants with histologically or cytologically confirmed advanced/metastatic malignant solid tumors, who have failed or have no available standard treatment;
• At least one measurable lesion as per RECIST v1.1 within 4 weeks prior to the first dose;
• An ECOG performance status score of 0-1 within 7 days prior to the first dose;
• Expected survival \> 3 months;
• 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);
• 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;
• 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);
• For participants with hepatocellular carcinoma, Child-Pugh score must be A;
• 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.

You may not qualify if:

• 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;
• History of serious ocular diseases, including: (1) keratoconjunctivitis sicca; (2) severe keratopathy; (3) moderate or severe xerophthalmia;
• 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;
• 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;
• Active systemic infectious diseases requiring intravenous antibiotics within 2 weeks prior to the first dose of the investigational product;
• 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.;
• 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;
• 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;
• 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;
• Presence of uncontrollable pleural effusion or pericardial effusion after appropriate intervention, or ascites requiring repeated drainage (once a month or more frequently);
• Use of strong inhibitors or inducers of CYP3A within 2 weeks prior to the first dose;
• Patients with active tuberculosis;
• Patients with a history of immunodeficiency, including human immunodeficiency virus (HIV)-positive or other acquired or congenital immunodeficiencies, or a history of organ transplantation;
• Patients with active HBV or HCV infection or HBV/HCV co-infection;
• Pregnant or lactating women;

Sponsors & Collaborators

• Shanghai Henlius Biotech: lead

Study Sites (7)

Macquarie University

North Ryde, New South Wales, 2109, Australia

NOT YET RECRUITING

GenesisCare St.Leonards

Saint Leonards, New South Wales, 2065, Australia

NOT YET RECRUITING

Peninsula and South Eastern Haematology and Oncology Group

Frankston, Victoria, 3199, Australia

NOT YET RECRUITING

Zhujiang Hospital of Southern Medical University

Guangzhou, Guangdong, 510280, China

NOT YET RECRUITING

Sun Yat-Sen University Cancer Center

Guangzhou, Guangzhou, 716099, China

RECRUITING

Shanghai General Hospital

Hongkou, Shanghai Municipality, 200080, China

RECRUITING

Shanxi Provincial Cancer Hospital

Taiyuan, Shanxi, 030000, China

NOT YET RECRUITING

Central Study Contacts

Ruihua Xu

CONTACT

86-20-87343468; Emailxurh@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2026
• First Posted: March 16, 2026
• Study Start: June 30, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): August 1, 2028
• Last Updated: July 2, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3); CN (4)