A Study of HLX42 in Advanced/Metastatic Solid Tumors

A Phase I Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Characteristics of HLX42 (Anti-EGFR ADC) in Patients With Advanced/Metastatic Solid Tumors

This study is an open-label first-in-human phase I clinical study to evaluate the safety and tolerability of HLX42.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor and NSCLC
• Intervention / Treatment: Drug: HLX42

Detailed Description

The first stage: This study is an open-label first-in-human phase I clinical study to evaluate the safety and tolerability of HLX42 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 HLX42 at different doses via intravenous infusion. The DLT observation period lasts for 3 weeks after the first administration of HLX42.

The second stage: This is a randimazation, open label, 2 arms, muticentral clinical study, about 30 patients in each arm, the total sample size is about 60. Eligible subjects will be randomized in a 1:1 ratio: Group A: HLX42 2.5 mg/kg; Group B: HLX42 2.0 mg/kg. Stratification: tumor tissue type(adenocarcinoma or squamous carcinoma), EGFR-sensitive mutation status (mutant or wild-type or missing).

• Study Type: Interventional
• Enrollment (Estimated): 102
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yilong Wu, Dr.; Phone Number: 020-83827812; Email: syylwu@live.cn
• Study Contact Backup: Name: Huajun Chen, Dr.; Phone Number: 020-83827812; Email: chjdoctor@163.com

Study Locations

• China
  • Guangzhou
    • Guangdong, Guangzhou, China
      • Recruiting
      • Guangdong Provincial People's Hospital
      • Contact: Huajun Chen, Dr.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. ≥ 18 years and ≤ 75 years at the time of signing the ICF, male or female;
2. 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(stage 1); Patients with histologically or cytologically confirmed advanced/metastatic malignant NSCLC, who are refractory to or intolerable with standard treatment, or for which no standard treatment is available(stage 2);
3. At least one measurable lesion as per RECIST 1.1；
4. An ECOG performance status score of 0-1；
5. Life expectancy > 3 months;
6. Adequate organ functions as confirmed by laboratory tests within 7 days prior to the first administration of the investigational product;
7. For patients with hepatocellular carcinoma, Child-Pugh score must be A;

Exclusion Criteria:

1. 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. The histopathological type is large cell carcinoma, adenosquamous carcinoma, other types (including but not limited to sarcomatoid carcinoma, lymphoepithelioma-like carcinoma, NUT carcinoma, etc.), or contains neuroendocrine pathological components, etc. (stage 2)；
3. History of (non-infectious) ILD requiring the use of steroids, current ILD, or suspected ILD that cannot be ruled out by imaging at screening;
4. Subjects who are allergic to protein preparations/ monoclonal antibodies/ any component in the formulation of the investigational product;
5. Subjects with known previous serious eye disorders;
6. Active systemic infectious diseases requiring intravenous antibiotics within 2 weeks prior to the first administration of the investigational product;
7. Any poorly-controlled cardiovascular and cerebrovascular clinical symptoms or diseases;
8. 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;
9. Patients who have received long-term systemic steroids treatment (equivalent to prednisone > 10 mg/day) or immunosuppressive agents of any other forms, which should be discontinued at least 2 weeks prior to the first infusion of the investigational product;
10. Patients who have used potent CYP2D6/CYP3A inhibitors or inducers within 2 weeks prior to the first administration;
11. Patients who have history of immunodeficiency, including HIV infection or other acquired or congenital immunodeficiencies, or history of organ transplantation;
12. Patients with active HBV or HCV infection or HBV/HCV co-infection;
13. Pregnant or lactating women;
14. 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HLX42; 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).	Drug: HLX42; HLX42 is an anti-EGFR monoclonal antibody conjugated with a novel high potency DNA topoisomerase I (topo I) inhibitor, with a drug-antibody-ratio (DAR) of 8.; Other Names: Anti-EGFR ADC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Dose-Limiting Toxicity (DLT) of HLX42 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 HLX42.	From first dose to the end of Cycle 1 (each cycle is 3 weeks).
The maximum tolerated dose (MTD) of HLX42	The highest dose level, at which DLT is observed in no more than one of 6 evaluable patients, is defined as MTD of HLX42.	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
Number of subjects experiencing adverse events	Frequency and seriousness of treatment emergent adverse events (TEAEs).	Day 1 through 90 days after last dose.
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.	up to approximately up to 24 months
Cmax	Maximum serum concentration (Cmax) of HLX42.	Up to 21 days after the first dose
Tmax	Time to maximum serum concentration (Tmax) of HLX42.	Up to 21 days after the first dose
T1/2	Half-life (T1/2) of HLX42.	Up to 21 days after the first dose
ADA (anti-drug antibody)	Incidence and titer of ADA of HLX42.	approximately up to 24 months
Nab (neutralizing antibody)	Incidence and titer of Nab of HLX42.	approximately up to 24 months

Collaborators and Investigators

• Sponsor: Shanghai Henlius Biotech
• Investigators: Principal Investigator: Yilong Wu, Dr., Guangdong Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2024
• Primary Completion (Estimated): September 2, 2026
• Study Completion (Estimated): June 14, 2027

Study Registration Dates

• First Submitted: January 8, 2024
• First Submitted That Met QC Criteria: January 8, 2024
• First Posted (Actual): January 18, 2024

Study Record Updates

• Last Update Posted (Actual): September 22, 2025
• Last Update Submitted That Met QC Criteria: September 17, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: HLX42-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: Yes
• Studies a U.S. FDA-regulated device product: No