Advanced or Metastatic Solid Tumors
Conditions
Brief 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.
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.
Interventions
BIOLOGICALHLX60 combined with HLX10
five various doses of HLX60 combined with flat dose of HLX10
Sponsors
Shanghai Henlius Biotech
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse event | Through study completion, assessed up to 2 years. | 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. |
| Incidence of DLT | Up to 3 weeks. | 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. |
| MTD | Up to 3 weeks. | The maximum tolerated dose (MTD) of HLX60 combined with HLX10 |
| RP2D | Through study completion, assessed up to 2 years. | The recommended phase II dose (RP2D) of HLX60 combined with HLX10 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax | 1 year | time to reach Cmax (Tmax) |
| t1/2 | 1 year | elimination half-life (t1/2) |
| AUC | 1 year | area under the serum concentration-time curve (AUC) |
| Objective response rate (ORR) | Through study completion, assessed up to 2 years. | Percentage of patients with complete response or partial response determined by investigators according to RECIST v1.1 |
| immunogenicity of HLX60 | 1 year | Incidence of HLX60 anti-drug antibody (ADA) and neutralizing antibody (NAb) |
| Potential prognostic and predictive biomarkers | 1 year | include the expressions of GARP, PD-L1 in tumor tissues and soluble GARP in peripheral blood. |
| PD | 1 year | include the GARP receptor occupancy on Treg cells, tumor infiltrating lymphocytes (TILs), FOXP3, pSMAD 2/3 in tumor tissues. |
| Progression-free survival (PFS) | Through study completion, assessed up to 2 years. | 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. |
| Overall survival(OS) | Through study completion, assessed up to 2 years. | OS is defined as the time from the first administration of HLX60 to death due to any cause. |
| Cmax | 1 year | serum concentration (Cmax) |
Countries
Australia
Outcome results
None listed