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

An Open-label, Multi-center Phase I Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of SHR-4602 in Subjects With HER2-expressing or HER2-mutated Locally Advanced or Metastatic Solid Tumors

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 Overview

• Status: Withdrawn
• Conditions: HER2-expressing or HER2-mutated Locally or Metastatic Solid Tumors
• Intervention / Treatment: Drug: SHR-4602

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Scientia Clinical Research Limited
    • Sydney, New South Wales, Australia, 2109
      • Macquarie University
  • Queensland
    • Brisbane, Queensland, Australia, 4101
      • Icon Cancer Centre South Brisbane
  • South Australia
    • Adelaide, South Australia, Australia, 500
      • Cancer Research SA
  • Victoria
    • Frankston, Victoria, Australia, 3199
      • Peninsula & South Eastern Haematology and Oncology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

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: SHR-4602 Dose level 1 : 2.0 mg/kg, Dose level 2 : 2.5mg/kg	Drug: SHR-4602; SHR-4602 will be administered through IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Cmax are the maximum observed plasma concentrations of SHR-4602, total antibodies, and free toxin after the first dose, directly observed from data.	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.	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.	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.	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	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	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.	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	Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year
CL	CL is the clearance	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	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.	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	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.	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.	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	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
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.	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.	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

Collaborators and Investigators

• Sponsor: Atridia Pty Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): December 14, 2025
• Study Completion (Estimated): September 12, 2026

Study Registration Dates

• First Submitted: August 15, 2024
• First Submitted That Met QC Criteria: August 15, 2024
• First Posted (Actual): August 19, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 5, 2025
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: SHR-4602-102

Drug and device information, study documents

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