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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Advanced or Metastatic Solid Tumors

Intervention / Treatment
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* Biological: HLX60 combined with HLX10


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HLX60 combined with HLX10<br> | Biological: HLX60 combined with HLX10<br>* five various doses of HLX60 combined with flat dose of HLX10<br>|

What is the study measuring?
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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 |