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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05494918




Registration number
NCT05494918
Ethics application status
Date submitted
4/08/2022
Date registered
10/08/2022
Date last updated
14/10/2022

Titles & IDs
Public title
First-In-Human Study in Subjects With Advanced or Metastatic Solid Malignant Tumors
Scientific title
A Phase I, Multi-center, Open-label, Dose Escalation, First-In-Human Study to Assess the Safety, Tolerability and Pharmacokinetics of JSKN003 in Subjects With Advanced or Metastatic Solid Malignant Tumors
Secondary ID [1] 0 0
JSKN003-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors 0 0
Metastatic Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - JSKN003

Experimental: Dose escalation - It's a dose escalation to identify the Maximum Tolerated dose (MTD) , recommended dose for expansion (RDE) or recommended Phase II dose (RP2D) of JSKN003, guided by the modified ADT design and BOIN design.


Treatment: Drugs: JSKN003
JSKN003 is to be administered via intravenous (IV) dose
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
MTD
Timepoint [1] 0 0
Postdose of last participant up to 1 year
Primary outcome [2] 0 0
Preliminary RDE/RP2D
Timepoint [2] 0 0
Postdose of last participant up to 1 year
Primary outcome [3] 0 0
DLTs
Timepoint [3] 0 0
Baseline up to 21 days after the first dose
Primary outcome [4] 0 0
Adverse Events
Timepoint [4] 0 0
Baseline up to 30 days after the last dose of study drug, up to 1 year
Secondary outcome [1] 0 0
Cmax of JSKN003
Timepoint [1] 0 0
Post last dose up to Day 90
Secondary outcome [2] 0 0
Tmax of JSKN003
Timepoint [2] 0 0
Post last dose up to Day 90
Secondary outcome [3] 0 0
AUC of JSKN003
Timepoint [3] 0 0
Post last dose up to Day 90
Secondary outcome [4] 0 0
Terminal Elimination Half-life (t1/2)
Timepoint [4] 0 0
Post last dose up to Day 90
Secondary outcome [5] 0 0
ORR
Timepoint [5] 0 0
Postdose of last participant up to 1 year
Secondary outcome [6] 0 0
TTR
Timepoint [6] 0 0
Postdose of last participant up to 1 year
Secondary outcome [7] 0 0
DoR
Timepoint [7] 0 0
Postdose of last participant up to 1 year
Secondary outcome [8] 0 0
PFS
Timepoint [8] 0 0
Postdose of last participant up to 1 year
Secondary outcome [9] 0 0
Anti-JSKN003 antibody
Timepoint [9] 0 0
Post last dose up to Day 90

Eligibility
Key inclusion criteria
1. Be willing and able to provide signed informed consent form (ICF) for the trial.
2. Male or female, 18 years of age or older; willing and able to comply with study requirements.
3. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 with no deterioration within 2 weeks of scheduled study treatment, and life expectancy = 12 weeks.
4. Must have a pathologically documented advanced/unresectable or metastatic solid malignant tumor with HER-2 expression (IHC = 1+) that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
5. Baseline measurable disease according to RECIST 1.1. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
6. Adequate organ function assessed within 7 days prior to first trial treatment [had not received blood transfusion, erythropoietin (EPO), granulocyte colony stimulating factor (G-CSF) or other relevant medical support within 14 days before the administration of the investigational product].
7. Have adequate treatment washout period before first trial treatment.
8. Have LVEF = 50% by either echo cardiography (ECHO) or multiple-gated acquisition (MUGA) within 28 days prior to first trial treatment.
9. Female or male subjects of childbearing potential should be willing to use a highly effective method of contraception (with a failure rate of less than 1.0% per year) from first study treatment to 180 days after completion of the trial treatment. Female of childbearing potential should have a negative pregnancy test within 7 days prior to first trial treatment (childbearing potential is defined as premenopausal females without documented tubal ligation or hysterectomy, or postmenopausal females within 1 year).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Clinically active central nervous system (CNS) metastases, defined as untreated and symptomatic, with following exceptions:

* Clinically stable through MRI/CT scans (at least 2 consecutive scans within prior 6 months including 1 scan within 28 days prior to screening) and no progressive or uncontrolled neurologic symptoms or signs (e.g., seizures, headaches, central nausea/emesis, progressive neurologic deficits, papilledema) for at least 4 weeks prior to the first treatment.
* Any untreated asymptomatic brain metastases not requiring immediate local or systemic therapy (e.g., mannitol or corticosteroids).
* Leptomeningeal metastasis is excluded from the study entry.
2. Concurrent malignancy within 5 years prior to entry other than adequately treated cervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cell carcinoma, prostate cancer, thyroid cancer not requiring treatment, ductal carcinoma in situ of the breast, or <T1 urothelial carcinoma.
3. Prior treatment with an antibody-drug conjugate (ADC) which consists of a topoisomerase I inhibitor derivative.
4. History of uncontrolled intercurrent illness including but not limited to:

* Active HBV or HCV infection. If HBsAg and HCV antibody positive, HBV DNA and HCV RNA assay should be performed. Subjects are eligible if HBV DNA = 500 UI/ml (or 2000 copies/ml) or HCV RNA negative.
* Known HIV infection or known history of acquired immune deficiency syndrome (AIDS);
* Active tuberculosis infection.
* Active infection within 4 weeks prior to the first dose of trial treatment that require the use of systemic antibiotics = 7 days.
* Hypertension uncontrolled by standard therapies (not stabilized to 160/100 mmHg);
* Clinically significant (that is, active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrolment), myocardial infarction (< 6 months prior to enrolment), unstable angina pectoris (< 6 months prior to enrolment), congestive heart failure (New York Heart Association Classification Class II-IV) or serious cardiac arrhythmia requiring medication (including corrected QT interval prolongation of > 470 msec for women and > 450 for men calculated according to Fridericia and/or pacemaker or prior diagnosis of congenital long QT syndrome;
* Serious nonhealing wound, ulcer or bone fracture.
5. Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids or current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by image at screening.
6. Previous severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection either suspected or confirmed within 4 weeks prior to screening. Acute symptoms will be excluded, or must have resolved and based on investigator assessment, there are no sequela that would place participant at a higher risk of receiving investigational treatment.
7. Subjects with ascites, pleural effusion, pericardial effusion which cannot be controlled by appropriate interventions.
8. Have unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia, grade 2 hypoparathyroidism) related to prior anticancer therapy and stable anemia (i.e., untransfused Hb = 9 g/dL without the need for supportive transfusion within 2 weeks of screening) not yet resolved to grade = 1 (NCI-CTCAEV5.0).
9. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses = 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. A brief course of corticosteroids for the prophylaxis (e.g., contrast dye allergy) or treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
10. History of life-threatening hypersensitivity or known to be allergic to protein drugs or recombinant proteins or excipients in JSKN003 drug formulation.
11. Prior history of Herceptin induced anaphylaxis, angioedema, or severe hypotension.
12. Other conditions that, in the investigators' opinion, would make subjects inappropriate to participate in this study, such as a history of mental illness, alcoholism or drug abuse.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/09/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/12/2024
Actual
Sample size
Target
45
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Breast Cancer Research Centre - Perth
Recruitment postcode(s) [1] 0 0
6009 - Perth

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Alphamab (Australia) Co Pty Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Arlene Chan
Address 0 0
Breast Cancer Research Centre-WA,Hollywood Consulting Centre
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Jeannette Devoto
Address 0 0
Country 0 0
Phone 0 0
61 8 6500 5555
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT05494918