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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced or Metastatic Solid Tumors
• Intervention / Treatment: Biological: HLX60 combined with HLX10

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jone park, PhD; Phone Number: 61298123533; Email: jone.park@mqhealth.org.au

Study Locations

• Australia
  • Sydney, Australia
    • Macquarie University Hospital & Nepean Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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/TGFβ complex antibody therapy.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
MTD	The maximum tolerated dose (MTD) of HLX60 combined with HLX10	Up to 3 weeks.
RP2D	The recommended phase II dose (RP2D) of HLX60 combined with HLX10	Through study completion, assessed up to 2 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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.
Cmax	serum concentration (Cmax)	1 year
Tmax	time to reach Cmax (Tmax)	1 year
t1/2	elimination half-life (t1/2)	1 year
AUC	area under the serum concentration-time curve (AUC)	1 year
PD	include the GARP receptor occupancy on Treg cells, tumor infiltrating lymphocytes (TILs), FOXP3, pSMAD 2/3 in tumor tissues.	1 year
immunogenicity of HLX60	Incidence of HLX60 anti-drug antibody (ADA) and neutralizing antibody (NAb)	1 year
Potential prognostic and predictive biomarkers	include the expressions of GARP, PD-L1 in tumor tissues and soluble GARP in peripheral blood.	1 year

Collaborators and Investigators

• Sponsor: Shanghai Henlius Biotech

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2022
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: July 6, 2022
• First Submitted That Met QC Criteria: August 1, 2022
• First Posted (Actual): August 2, 2022

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 14, 2024
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: HLX60HLX10-FIH101

Drug and device information, study documents

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