A Trial of SHR-4602 Infusion in Patients With SHR-4602 in Subjects With HER2-expressing or HER2-mutated Locally Advanced or Metastatic Solid Tumors

Atridia Pty Ltd.

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Conditions

HER2-expressing or HER2-mutated Locally or Metastatic Solid Tumors

Interventions

SHR-4602DRUG

SHR-4602 will be administered through IV infusion.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 Exclusion Criteria 1. Active brain metastases, carcinomatous meningitis/leptomeningeal metastases. 2. Have received surgery (eg. major surgerical treatment for cancer), chemotherapy, molecular targeted therapy, immunotherapy, cell therapy, or radiotherapy within 4 weeks prior to the first dose of investigational drug (palliative radiotherapy within 2 weeks prior to the first dose). 3. Participated in another clinical study with the last dose of study drug received in less than 4 weeks prior to the first dose. 4. Subjects with toxicities and/or complications from prior treatment not recovered to NCI-CTCAE Grade ≤ 1. 5. History of pleural fluid, ascites, or pericardial effusion requiring intervention within 2 weeks prior to the first dose. 6. History of active autoimmune diseases. 7. History of hereditary or acquired bleeding disorders or thrombotic tendency 8. Active hepatitis B (defined as hepatitis B virus surface antigen \[HBsAg\] positive and serum HBV-DNA copy ≥ 500 IU/mL), hepatitis C 9. History of severe infection within the past 30 days, including but not limited to bacteremia, severe sepsis, pneumonia requiring hospitalization 10. Other malignancies currently or within the past 5 years, except for cured cervical carcinoma in situ 11. Allergy to any component or excipient of the SHR-4602 product, 12. History of severe medical, psychiatric, or social conditions deemed by the investigator to be likely to interfere with a subject's ability to understand, consent, cooperate and participate in the study. 13. Patients with Grade≥2 peripheral neuropathy, except for those with mild symptoms that do not require treatment

Locations (5)

Scientia Clinical Research Limited

Randwick, New South Wales, Australia

Macquarie University

Sydney, New South Wales, Australia

Icon Cancer Centre South Brisbane

Brisbane, Queensland, Australia

Cancer Research SA

Adelaide, South Australia, Australia

Outcomes

Primary Outcomes

the phase II dose (RP2D) of SHR-4602

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.

Time frame: 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

Secondary Outcomes

Cmax

Cmax are the maximum observed plasma concentrations of SHR-4602, total antibodies, and free toxin after the first dose, directly observed from data.

Time frame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year

Tmax

Tmax is the time point when Cmax is observed.

Time frame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year

Css, max,

Css, max are steady-state maximum concentrations of SHR-4602, total antibodies, and free toxin during multiple dosing, and are directly observed from data.

Time frame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year

Css, min

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.

Time frame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year

AUC0-t

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

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Peninsula & South Eastern Haematology and Oncology Group

Frankston, Victoria, Australia

Time frame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year

AUC0-∞

AUC0-∞ are the areas under the drug concentration-time curve of SHR-4602, total antibodies, and free toxin (ER300) from time 0 to infinity

Time frame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year

AUCτ

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.

Time frame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year

t1/2

t1/2 is he elimination half-life

Time frame: 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

Time frame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year

Vss

Vss is volume of distribution

Time frame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year

MRT

MRT is the mean residence time, of SHR-4602, total antibodies, or free toxin. Those values are calculated using the non-compartmental model.

Time frame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year

Rac

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

Time frame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year

anti-SHR-4602 antibody (ADA)

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.

Time frame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year

Objective Response Rate (ORR)

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.

Time frame: 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

Duration of Response (DoR)

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

Disease Control Rate (DCR)

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.

Time frame: 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.

Progression Free Survival (PFS)

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.

Time frame: 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