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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06226766




Registration number
NCT06226766
Ethics application status
Date submitted
22/12/2023
Date registered
26/01/2024
Date last updated
28/03/2024

Titles & IDs
Public title
JSKN033 in Patients With Advanced or Metastatic Solid Malignant Tumors
Scientific title
Phase I/II Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of JSKN033 in Patients With Advanced or Metastatic Solid Malignant Tumors
Secondary ID [1] 0 0
JSKN033-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - JSKN033 Injection

Experimental: Dose escalation/expansion - The dose escalation phase will utilize single patient accelerated dose titration (ADT) for dose level 1 (1.1 mg/kg , SC, QW) and dose level 2 (2.3 mg/kg, SC, QW), followed by dose level 3 (4.5 mg/kg, SC, QW), dose level 4 (5.6 mg/kg, SC, QW) and dose level 5 (6.7 mg/kg, SC,QW), which will all be enrolled and monitored using the "3+3" design, aimed at determining the MTD/RP2D of JSKN033.
After or during dose escalation, SMC will select 1-2 dose levels to expand with 10-30 additional patients with gastrointestinal tumor with HER2 expression each dose level for further exploration of the efficacy and safety of JSKN033.


Treatment: Drugs: JSKN033 Injection
JSKN033 is a combination drug product comprised of JSKN003 and envafolimab for subcutaneous injection.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs), assessed by CTCAE V5.0
Timepoint [1] 0 0
Postdose of last participant up to 1 year
Primary outcome [2] 0 0
RP2D( recommend Phase II dose)
Timepoint [2] 0 0
Postdose of last participant up to 1 year
Primary outcome [3] 0 0
DLTs (Dose-limiting toxicities)
Timepoint [3] 0 0
Baseline up to 21 days after the first dose
Primary outcome [4] 0 0
Objective Response Rate (ORR) Following Treatment With JSKN033 in Participants With Advanced Solid Malignant Tumors
Timepoint [4] 0 0
From 6 weeks postdose of last participant up to 1 years
Secondary outcome [1] 0 0
Maximum concentration (Cmax)
Timepoint [1] 0 0
Postdose of last participant up to 1 year
Secondary outcome [2] 0 0
Time at which Cmax is reached (Tmax)
Timepoint [2] 0 0
Postdose of last participant up to 1 year
Secondary outcome [3] 0 0
Area under the drug concentration-time curve (AUC) to the last observable concentration (AUClast)
Timepoint [3] 0 0
Postdose of last participant up to 1 year
Secondary outcome [4] 0 0
Progression-Free Survival (PFS) Following Treatment With JSKN033 in Participants
Timepoint [4] 0 0
Postdose of last participant up to 1 year
Secondary outcome [5] 0 0
Duration of Response (DoR) Following Treatment With JSKN033 in Participants
Timepoint [5] 0 0
Postdose of last participant up to 1 year
Secondary outcome [6] 0 0
Overall Survival (OS) Following Treatment With JSKN033 in Participants
Timepoint [6] 0 0
Postdose of last participant up to 1 year

Eligibility
Key inclusion criteria
1. Be willing and able to provide written informed consent form (ICF) for the trial.

2. Male or female, 18 years of age or older; willing and able to complete all required
procedures of study.

3. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1, and life
expectancy = 12 weeks.

4. Must have a pathologically documented advanced unresectable or metastatic solid
malignant tumor (gastrointestinal tumor for dose expansion phase) with HER2 expression
(IHC =1+) that is refractory to or intolerable with standard treatment, or for which
no effective standard treatment is available. HER2 mutation in patients with NSCLC is
also regarded as HER2 expression.

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 dose.

8. Have LVEF =50% by either echo cardiography (ECHO) or multiple-gated acquisition (MUGA)
within 28 days prior to first dose.

9. Female or male patients 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 study 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. Patients with untreated active brain metastases or meningeal or spinal cord metastases
are excluded. If the subject has received treatment for brain metastases and the
metastases are stable (as evidenced by brain imaging within 28 days prior to study
treatment showing stable disease, no new lesions, and no new neurological symptoms,
and no requirement for steroids for at least 14 days prior to study treatment), they
may be eligible for enrollment.

2. Concurrent malignancy within 5 years prior to first dose 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 concurrent illness.

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. Patients 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 not yet resolved to grade = 1 (NCI-CTCAEV5.0).

9. Patients 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 JSKN033 drug formulation.

11. Prior history of anti-HER2 therapy induced angioedema, or severe hypotension and
Severe allergic reactions to other antibody drugs or topoisomerase I inhibitors.

12. Other conditions that, in the investigators' opinion, would make patients
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
N/A
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/Phase 2
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
18/01/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/10/2026
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Scientia Clinical Research - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Jiangsu Alphamab Biopharmaceuticals Co., Ltd
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study is an open-label, multicenter, first-in-human, Phase I/II (dose escalation and
dose expansion) study to evaluate the safety, tolerability, PK, immunogenicity and efficacy
of JSKN033 in patients with advanced unresectable or metastatic solid malignant tumors that
are expected to be HER2 expression (IHC = 1+).
Trial website
https://clinicaltrials.gov/ct2/show/NCT06226766
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Charlotte Lemech
Address 0 0
Scientia Clinical Research
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Grace Yueun Hwang
Address 0 0
Country 0 0
Phone 0 0
+61 29382 5873
Fax 0 0
Email 0 0
grace.hwang@scientiaclinicalresearch.com.au
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06226766