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Trial Title:
First-In-Human Study in Subjects With Advanced or Metastatic Solid Malignant Tumors
NCT ID:
NCT05494918
Condition:
Advanced Solid Tumors
Metastatic Solid Tumors
Conditions: Official terms:
Neoplasms
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Intervention model description:
The starting dose of JSKN003 is 1.0 mg/kg, followed by 2.1, 4.2, 5.3, 6.3, 7.3, 8.4, 9.4
and 10.5 mg/kg.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
JSKN003
Description:
JSKN003 is to be administered via intravenous (IV) dose
Arm group label:
Dose escalation
Other name:
anti-Her2 ADC JSKN003
Summary:
This study is an open-label, multicenter, first-in-human, Phase I, dose escalation study
to evaluate the safety, tolerability, PK, and preliminary anti-tumor activity of JSKN003
in subjects with advanced inoperable or metastatic solid malignant tumors that are
expected to be HER2 expression.
Detailed description:
The dose escalation study will utilize single patient accelerated dose titration for the
first two dose levels, 1.0 and 2.1 mg/kg, followed by dose cohorts 4.2, 5.2, 6.3, 7.3,
and 8.4 mg/kg which will all be enrolled and monitored using the Bayesian optimal
interval design, aimed at determining the MTD, RDE/RP2D of JSKN003. The dose-escalation
of 9.4 mg/kg and 10.5 mg/kg should be determined per discussion between Safety Monitoring
Committee and sponsor if deemed necessary, the SMC had the right of deciding to
dose-escalate at other dose levels . Moreover, the SMC is also responsible for deciding
the MTD and the recommended dose level for dose-expansion study.
Enrolled patients will be sequentially assigned to the planned dose levels as required by
the protocol and treated with JSKN003 IV Q3W to observe the occurrence of treatment
related AEs and dose limiting toxicities. The DLT observation period is 21 days from
administration of the first dose of JSKN003.
The study will use a modified ADT design and BOIN design for dosing cohort management to
determine the MTD and RDE/RP2D. The starting dose of JSKN003 is 1.0 mg/kg, followed by
2.1, 4.2, 5.3, 6.3, 7.3, 8.4, 9.4 and 10.5 mg/kg. The investigational product will be
administered on Day 1 every 3 weeks via intravenous infusion, and the first cycle of
JSKN003 treatment is for DLT evaluation.
Criteria for eligibility:
Criteria:
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).
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 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Breast Cancer Research Centre
Address:
City:
Perth
Zip:
6009
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Jeannette Devoto
Phone:
61 8 6500 5555
Email:
jeannette.devoto@bcrc-wa.com.au
Contact backup:
Last name:
Silvie Radmil
Phone:
0061 8 6500 5555
Email:
silvie.radmil@bcrc-wa.com.au
Start date:
September 2, 2022
Completion date:
December 30, 2024
Lead sponsor:
Agency:
Alphamab (Australia) Co Pty Ltd.
Agency class:
Industry
Source:
Alphamab (Australia) Co Pty Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05494918