Clinical trial NCT06560138: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: HER2-expressing or HER2-mutated Locally or Metastatic Solid Tumors
Lead sponsor: Atridia Pty Ltd.
Sponsor class: INDUSTRY
First posted: 2024-08-19
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: SHR-4602 injection only
Primary purpose: TREATMENT

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.


Eligibility 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:

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

Primary outcomes:
measure: the phase II dose (RP2D) of SHR-4602
timeFrame: 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:
measure: Cmax
timeFrame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year
measure: Tmax
timeFrame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year
measure: Css, max,
timeFrame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year
measure: Css, min
timeFrame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year
measure: AUC0-t
timeFrame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year
measure: AUC0-∞
timeFrame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year
measure: AUCτ
timeFrame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year
measure: t1/2
timeFrame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year
measure: CL
timeFrame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year
measure: Vss
timeFrame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year
measure: MRT
timeFrame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year
measure: Rac
timeFrame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year
measure: anti-SHR-4602 antibody (ADA)
timeFrame: Pre-set time points: from C1D1 within 1 hour pre-dose to 30 ± 7 days, after EOT up to 1 year
measure: Objective Response Rate (ORR)
timeFrame: 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
measure: Duration of Response (DoR)
timeFrame: 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
measure: Disease Control Rate (DCR)
timeFrame: 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.
measure: Progression Free Survival (PFS)
timeFrame: 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
Other outcomes:
Locations:
city: Randwick
country: Australia
facility: Scientia Clinical Research Limited
state: New South Wales
city: Sydney
country: Australia
facility: Macquarie University
state: New South Wales
city: Brisbane
country: Australia
facility: Icon Cancer Centre South Brisbane
state: Queensland
city: Adelaide
country: Australia
facility: Cancer Research SA
state: South Australia
city: Frankston
country: Australia
facility: Peninsula & South Eastern Haematology and Oncology Group
state: Victoria
Study officials:
References: