First-In-Human Study in Subjects With Advanced or Metastatic Solid Malignant Tumors

NCT05494918 | Completed Phase 1

• 1 other identifier: JSKN003-101
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advanced Solid Tumors; Metastatic Solid Tumors

Outcome Measures

Primary Outcomes (4)

• MTD

  Maximum tolerated dose

  Postdose of last participant up to 1 year

• Preliminary RDE/RP2D

  recommended dose for expansion / recommended phase 2 dose

  Postdose of last participant up to 1 year

• DLTs

  Dose Limiting Toxicities

  Baseline up to 21 days after the first dose

• Adverse Events

  Incidence and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs)

  Baseline up to 30 days after the last dose of study drug, up to 1 year

Secondary Outcomes (9)

• Cmax of JSKN003

  Post last dose up to Day 90

• Tmax of JSKN003

  Post last dose up to Day 90

• AUC of JSKN003

  Post last dose up to Day 90

• Terminal Elimination Half-life (t1/2)

  Post last dose up to Day 90

• ORR

  Postdose of last participant up to 1 year

Study Arms (1)

Dose escalation

EXPERIMENTAL

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.

Drug: JSKN003

Interventions

JSKN003 DRUG

JSKN003 is to be administered via intravenous (IV) dose

Also known as: anti-Her2 ADC JSKN003

Dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide signed informed consent form (ICF) for the trial.
• Male or female, 18 years of age or older; willing and able to comply with study requirements.
• 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.
• 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.
• 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.
• Adequate organ function assessed within 7 days prior to first trial treatment \[had not received blood transfusion, erythropoietin (EPO), granulocyte colony stimulating factor (G-CSF) or other relevant medical support within 14 days before the administration of the investigational product\].
• Have adequate treatment washout period before first trial treatment.
• Have LVEF ≥ 50% by either echo cardiography (ECHO) or multiple-gated acquisition (MUGA) within 28 days prior to first trial treatment.
• 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).

You may not qualify if:

• 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.
• 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.
• Prior treatment with an antibody-drug conjugate (ADC) which consists of a topoisomerase I inhibitor derivative.
• 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.
• 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.

Sponsors & Collaborators

• Alphamab (Australia) Co Pty Ltd.: lead

Study Sites (1)

Breast Cancer Research Centre

Perth, Western Australia, 6009, Australia

Location

Study Officials

• Arlene Chan

  Breast Cancer Research Centre-WA,Hollywood Consulting Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 4, 2022
• First Posted: August 10, 2022
• Study Start: September 2, 2022
• Primary Completion: April 15, 2025
• Study Completion: April 15, 2025
• Last Updated: August 22, 2025

Record last verified: 2025-08

Locations

AU (1)