A Study to Investigate the Safety, Tolerability and Efficacy of HLX60 Combination With HLX10 in Subjects With Advanced or Metastatic Solid Tumors

Advanced or Metastatic Solid Tumors Clinical Trial

Official title:

A Phase 1 Clinical Study to Investigate the Safety, Tolerability and Efficacy of HLX60 (Anti-GARP Monoclonal Antibody) Combination With HLX10 (Anti-PD-1 Monoclonal Antibody) in Subjects With Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05483530
• Other study ID #: HLX60HLX10-FIH101
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: December 14, 2022
• Est. completion date: August 2025

Study information

• Verified date: August 2023
• Source: Shanghai Henlius Biotech
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to evaluate the safety and tolerability of HLX60 combined with HLX10 in order to determine the maximum tolerated dose (MTD) and Recommended Phase 2 dose (RP2D) and to evaluate the preliminary efficacy for each combination regimen.

Description:

Accelerated titration and "3 + 3" dose escalation were used in this trial . various doses of HLX60(anti-GARP) combined with HLX10(anti-PD-1) by intravenous infusion.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: August 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with histologically or cytologically confirmed advanced malignant solid tumor, who have failed or cannot receive the standard treatment;
• With at least one evaluable lesion according to RECIST v1.1 (for solid tumors);
• Patients must be able to supply adequate tumor tissue for biomarker (including the expression of PD-L1, GARP) analyses;
• Life expectancy longer than three months;
• Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.

Exclusion Criteria:

• Has a concurrently active second malignancy, other than adequately treated non-melanoma skin cancers, in situ melanoma or in situ cervical cancer. Participants with history of the second malignancy have been disease-free for <3 years.
• Has a history of (non-infectious) interstitial lung disease (ILD) that required steroids, currently has ILD, or when suspected ILD cannot be ruled out by imaging at screening.
• Participant has unresolved AEs = Grade 2 from prior anticancer therapy except for alopecia.
• Those who have received anti-GARP or anti-GARP/TGFß complex antibody therapy.

Related Conditions & MeSH terms

• Advanced or Metastatic Solid Tumors
• Neoplasms

Intervention

Biological:
• HLX60 combined with HLX10
five various doses of HLX60 combined with flat dose of HLX10

Locations

Country	Name	City	State
Australia	Macquarie University Hospital & Nepean Hospital	Sydney

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Henlius Biotech

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse event	Incidence and severity of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 for patients receiving study drug.	Through study completion, assessed up to 2 years.
Primary	Incidence of DLT	Ratio of the number of patients with DLT events in each dose group to the number of patients in the dose group during the DLT evaluation period.	Up to 3 weeks.
Primary	MTD	The maximum tolerated dose (MTD) of HLX60 combined with HLX10	Up to 3 weeks.
Primary	RP2D	The recommended phase II dose (RP2D) of HLX60 combined with HLX10	Through study completion, assessed up to 2 years.
Secondary	Objective response rate (ORR)	Percentage of patients with complete response or partial response determined by investigators according to RECIST v1.1	Through study completion, assessed up to 2 years.
Secondary	Progression-free survival (PFS)	PFS is defined as the time from the first administration of HLX60 and HLX10 to the first occurrence of disease progression or death due to any cause, whichever occurs first.	Through study completion, assessed up to 2 years.
Secondary	Overall survival(OS)	OS is defined as the time from the first administration of HLX60 to death due to any cause.	Through study completion, assessed up to 2 years.
Secondary	Cmax	serum concentration (Cmax)	1 year
Secondary	Tmax	time to reach Cmax (Tmax)	1 year
Secondary	t1/2	elimination half-life (t1/2)	1 year
Secondary	AUC	area under the serum concentration-time curve (AUC)	1 year
Secondary	PD	include the GARP receptor occupancy on Treg cells, tumor infiltrating lymphocytes (TILs), FOXP3, pSMAD 2/3 in tumor tissues.	1 year
Secondary	immunogenicity of HLX60	Incidence of HLX60 anti-drug antibody (ADA) and neutralizing antibody (NAb)	1 year
Secondary	Potential prognostic and predictive biomarkers	include the expressions of GARP, PD-L1 in tumor tissues and soluble GARP in peripheral blood.	1 year