HER2-expressing or HER2-mutated Locally or Metastatic Solid Tumors
Conditions
Brief summary
To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR-4602 in subjects with HER2-expressing or HER2-mutated locally advanced or metastatic solid tumors.
Interventions
DRUGSHR-4602
SHR-4602 will be administered through IV infusion.
Sponsors
Atridia Pty Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
SHR-4602 injection only
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Ability to understand the trial procedures and possible adverse events, voluntarily participate in the trial. 2. ECOG PS score 0 or 1 3. Life expectancy ≥ 12 weeks 4. Adequate bone marrow and other vital organ functions 5. Adequate liver function tests 6. HER 2 exprission advanced solid tumor
Exclusion criteria
Inclusion Criteria 1. Ability to understand the trial procedures and possible adverse events, voluntarily participate in the trial. 2. ECOG PS score 0 or 1 3. Life expectancy ≥ 12 weeks 4. Adequate bone marrow and other vital organ functions 5. Adequate liver function tests 6. HER 2 exprission advanced solid tumor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the phase II dose (RP2D) of SHR-4602 | From the time when the subjects sign the informed consent form to 45(±3) days after the last dose of SHR-4602, or the start of new anti-tumor treatment (whichever comes first).assessed for a maximum duration of up to 1 year | RP2D is defined as the dose of SHR-4602 recommended for efficacy study in Phase II. It will be the dose with promising clinical responses observed in the subjects, well tolerated by subjects without exceeding a pre-set number of adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | From the first date with measurable disease meeting the CR, PR or SD criteria, to the date of PD or death from any cause, whichever occurs first. assessed for a maximum duration of up to 3 years. | DCR refers to the proportion of subjects with a best overall response of CR, PR, or Stable Disease (SD). Subjects evaluated as SD should meet the criteria for SD at least once at a minimum of 6 weeks after enrolment. |
| Cmax | Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year | Cmax are the maximum observed plasma concentrations of SHR-4602, total antibodies, and free toxin after the first dose, directly observed from data. |
| Tmax | Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year | Tmax is the time point when Cmax is observed. |
| Css, max, | Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year | Css, max are steady-state maximum concentrations of SHR-4602, total antibodies, and free toxin during multiple dosing, and are directly observed from data. |
| Css, min | Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year | Css, min are the steady-state trough concentrations of SHR-4602, total antibodies, and free toxin during multiple dosing, and are directly observed from data. |
| AUC0-t | Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year | AUC0-t are the areas under the drug concentration-time curve of SHR-4602, total antibodies, and free toxin from time 0 to the last measurable concentration time point |
| AUC0-∞ | Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year | AUC0-∞ are the areas under the drug concentration-time curve of SHR-4602, total antibodies, and free toxin (ER300) from time 0 to infinity |
| AUCτ | Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year | AUCτ are the areas under the drug concentration-time curve of SHR-4602, total antibodies, and free toxin between two doses of SHR-4602 after multiple administrations. |
| Duration of Response (DoR) | From the first date with measurable disease meeting the CR or PR criteria, to the date of PD or death from any cause, whichever occurs first. assessed for a maximum duration of up to 3 years | DOR refers to the time from the first occurrence of CR or PR to Progression of Disease (PD) or death from any cause, whichever occurs first, in subjects with objective response. If the subject does not experience PD or death or is lost to follow-up at the end of study, DOR will be censored at the time of the last tumor evaluation. DOR will be estimated using the method of Kaplan-Meier |
| CL | Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year | CL is the clearance |
| Vss | Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year | Vss is volume of distribution |
| MRT | Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year | MRT is the mean residence time, of SHR-4602, total antibodies, or free toxin. Those values are calculated using the non-compartmental model. |
| Rac | Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year | Rac is the accumulation ratios of SHR-4602, total antibodies, or free toxin. It will be evaluated based on the ratio of exposure following multiple administrations to the single administration |
| anti-SHR-4602 antibody (ADA) | Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year | Approximately 4 mL of blood samples will be collected at pre-set time points and used for immunogenicity-related studies, which may include designation of in-study cut-points, analysis of anti-drug antibody (ADA) and neutralizing antibody, and target interference studies. All ADA assay results obtained will be listed. Samples positive for ADA will be analyzed for titers. The percentage of ADA positive subjects, time to ADA onset, ADA duration will be summarized by dose group. |
| Objective Response Rate (ORR) | From the first date with measurable disease meeting the CR or PR criteria, to the date of PD or death from any cause, whichever occurs first. assessed for a maximum duration of up to 3 years | ORR refers to the proportion of subjects with a best overall response of Complete/Partial Response (CR or PR) in subjects with measurable diseases by tumor imaging per RECIST v1.1. For subjects with CR or PR at the first evaluation, the efficacy should be confirmed 4 weeks later or at the next tumor imaging evaluation. |
| Progression Free Survival (PFS) | From the first dose of SHR-4602 to the first PD or death from any cause (whichever occurs first). assessed for a maximum duration of up to 3 years | PFS refers to the time from the first dose of SHR-4602 to the first PD or death from any cause (whichever occurs first) as assessed by the investigator. If the subject does not experience PD or death or receives other anti-tumor treatments at the end of study, PFS will be censored on the date of the last tumor assessment. PFS will also be estimated using the method of Kaplan-Meier. |
| t1/2 | Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year | t1/2 is he elimination half-life |
Countries
Australia
Outcome results
None listed