A Study of HLX42 in Advanced/Metastatic Solid Tumors

Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06210815
• Other study ID #: HLX42-FIH101
• Status: Recruiting
• Phase: Phase 1
• Start date: March 14, 2024
• Est. completion date: July 1, 2026

Study information

• Verified date: April 2024
• Source: Shanghai Henlius Biotech
• Contact: Yilong Wu, Dr.
• Phone: 020-83827812
• Email: syylwu[@]live.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: July 1, 2026
• Est. primary completion date: April 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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;

5. An ECOG performance status score of 0-1;

6. Life expectancy > 3 months;

7. Subjects should agree to provide archived tumor tissue specimens or agree to undergo a biopsy to collect tumor tissue for biomarker testing;

8. Adequate organ functions as confirmed by laboratory tests within 7 days prior to the first administration of the investigational product;

9. For patients with hepatocellular carcinoma, Child-Pugh score must be A;

10. 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. 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. History of (non-infectious) ILD requiring the use of steroids, current ILD, or suspected ILD that cannot be ruled out by imaging at screening;

3. Subjects who are allergic to protein preparations/ monoclonal antibodies/ any component in the formulation of the investigational product;

4. Subjects with known previous serious eye disorders;

5. Active systemic infectious diseases requiring intravenous antibiotics within 2 weeks prior to the first administration of the investigational product;

6. Any poorly-controlled cardiovascular and cerebrovascular clinical symptoms or diseases;

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;

8. 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;

9. Patients who have used potent CYP2D6/CYP3A inhibitors or inducers within 2 weeks prior to the first administration;

10. Patients who have history of immunodeficiency, including HIV infection or other acquired or congenital immunodeficiencies, or history of organ transplantation;

11. Patients with active HBV or HCV infection or HBV/HCV co-infection;

12. Pregnant or lactating women;

13. 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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

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.

Locations

Country	Name	City	State
China	Guangdong Provincial People's Hospital	Guangdong	Guangzhou

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Henlius Biotech

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).
Primary	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	Objective response rate (ORR)	Percentage of participants with complete response (CR) and partial response (PR) based on investigator assessment.	approximately up to 24 months
Secondary	Duration of response (DOR)	Length of time response continued based on investigator's assessment.	approximately up to 24 months.
Secondary	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
Secondary	Overall survival (OS)	Time from the date of enrollment to the date of death for any cause.	approximately up to 24 months
Secondary	Cmax	Maximum serum concentration (Cmax) of HLX42.	Up to 21 days after the first dose
Secondary	Tmax	Time to maximum serum concentration (Tmax) of HLX42.	Up to 21 days after the first dose
Secondary	T1/2	Half-life (T1/2) of HLX42.	Up to 21 days after the first dose
Secondary	ADA (anti-drug antibody)	Incidence and titer of ADA of HLX42.	approximately up to 24 months
Secondary	Nab (neutralizing antibody)	Incidence and titer of Nab of HLX42.	approximately up to 24 months
Secondary	Number of subjects experiencing adverse events	Frequency and seriousness of treatment emergent adverse events (TEAEs).	Day 1 through 90 days after last dose.